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Li X, Jiao G, Chen Y. A case-control study based on the National Health and Nutrition Examination Survey to evaluate the effects of human papilloma virus on bone health in women. BMC Med 2025; 23:75. [PMID: 39920637 PMCID: PMC11806905 DOI: 10.1186/s12916-025-03909-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 01/24/2025] [Indexed: 02/09/2025] Open
Abstract
BACKGROUND Human papillomavirus (HPV) infection and osteoporosis (OP) are global health concerns, with higher prevalence observed in women compared to men. However, the impact of HPV infection on bone health remains uncertain. METHODS This case-control study utilized data from the National Health and Nutrition Examination Survey (NHANES). Comparable datasets were created using nearest neighbor propensity score matching (PSM) at a ratio of 1:1. The association between HPV infection and bone mineral density (BMD) was analyzed using the Welch two-sample t-test. Furthermore, linear mixed models were employed for validation purposes. Restricted cubic spline (RCS) analysis and Kendall's tau-b tests were performed to explore the effect of different types of HPV infection on BMD. RESULTS Individuals with HPV infection (mean age 38.11 ± 11.32 years) had lower BMD in the femur and lumbar spine compared to uninfected individuals (mean age 37.92 ± 11.42 years). RCS analysis revealed that an increasing number of cooccurring HPV types in women was associated with lower BMD. Specifically, four HPV types were negatively associated with femur BMD, while 14 HPV types were negatively associated with lumbar spine BMD. Additionally, HPV types 53, 59, and 89 exhibited effects on both femur and lumbar spine BMD. CONCLUSIONS HPV infection is associated with a decrease in BMD, and co-infection with multiple types of HPV implies even lower BMD. Appropriately designed trials are needed to determine if interventions targeted at preventing HPV infection can have a protective effect on BMD.
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Affiliation(s)
- Xiang Li
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250000, China
- Department of Orthopedics, Qilu Hospital of Shandong University, No.107, Wenhuaxi Road, Jinan, Shandong, 250000, China
| | - Guangjun Jiao
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250000, China.
- Department of Orthopedics, Qilu Hospital of Shandong University, No.107, Wenhuaxi Road, Jinan, Shandong, 250000, China.
| | - Yunzhen Chen
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250000, China.
- Department of Orthopedics, Qilu Hospital of Shandong University, No.107, Wenhuaxi Road, Jinan, Shandong, 250000, China.
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Salimi B, Seifi S, Khosravi A, Shiari S, Moradi R, Daneshfard B, Mabani M. Histopathological Patterns of Lung Cancer in Iran: A Single-Center Study. ARCHIVES OF IRANIAN MEDICINE 2024; 27:501-507. [PMID: 39465525 PMCID: PMC11496601 DOI: 10.34172/aim.31133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Accepted: 07/27/2024] [Indexed: 10/29/2024]
Abstract
BACKGROUND Lung cancer (LC) is one of the leading causes of cancer-related deaths worldwide. In Iran, it is the second most common cause of cancer-related deaths for men and the third most common for women. This study aimed to examine the clinicopathological characteristics of Iranian patients with LC. METHODS Clinicopathological data of 1382 patients with primary LC diagnosed over 11 years (2012‒2023) at the "National Institute of Tuberculosis and Lung Disease" (NRITLD), Tehran, Iran, were retrospectively reviewed. RESULTS Adenocarcinoma was the most common type of cancer found in the patients (42.44%). The median age was 59.69 years (mean: 60.41 years) ranging 24-88 years. The mean male-to-female ratio was 3.65. Additionally, 65.84% of patients were smokers. The majority of patients (82.69 %) were diagnosed at an advanced stage (stage IV) of cancer. CONCLUSION Although some of our findings are consistent with those of previous LC studies, there are some discrepancies, especially concerning the smoking status and median age of the Iranian patients. Therefore, additional clinical and epidemiological studies are needed to determine the impact of non-smoking factors, such as environmental exposure and genetic predisposition, on the development of LC.
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Affiliation(s)
- Babak Salimi
- Research Center of Thoracic Oncology (RCTO), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Sharareh Seifi
- Research Center of Thoracic Oncology (RCTO), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Adnan Khosravi
- Research Center of Thoracic Oncology (RCTO), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Sara Shiari
- Research Center of Thoracic Oncology (RCTO), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Raana Moradi
- Research Center of Thoracic Oncology (RCTO), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Babak Daneshfard
- Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Persian Medicine Network (PMN), Universal Scientific Education and Research Network (USERN), Tehran, Iran
- Canadian College of Integrative Medicine, Montreal, Quebec, Canada
| | - Maryam Mabani
- Research Center of Thoracic Oncology (RCTO), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Science, Tehran, Iran
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Jin HT, Kim YS, Choi EK. Human papillomavirus and Merkel cell polyomavirus in Korean patients with nonsmall cell lung cancer: Evaluation and genetic variability of the noncoding control region. J Med Virol 2024; 96:e29880. [PMID: 39185678 DOI: 10.1002/jmv.29880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 07/23/2024] [Accepted: 08/13/2024] [Indexed: 08/27/2024]
Abstract
Human papillomavirus (HPV) is an important causative factor of cervical cancer and is associated with nonsmall cell lung cancer (NSCLC). Merkel cell polyomavirus (MCPyV) is a rare and highly fatal cutaneous virus that can cause Merkel cell carcinoma (MCC). Although coinfection with oncogenic HPV and MCPyV may increase cancer risk, a definitive etiological link has not been established. Recently, genomic variation and genetic diversity in the MCPyV noncoding control region (NCCR) among ethnic groups has been reported. The current study aimed to provide accurate prevalence information on HPV and MCPyV infection/coinfection in NSCLC patients and to evaluate and confirm Korean MCPyV NCCR variant genotypes and sequences. DNA from 150 NSCLC tissues and 150 adjacent control tissues was assessed via polymerase chain reaction (PCR) targeting regions of the large T antigen (LT-ag), viral capsid protein 1 (VP1), and NCCR. MCPyV was detected in 22.7% (34 of 150) of NSCLC tissues and 8.0% (12 of 150) of adjacent tissues from Korean patients. The incidence rates of HPV with and without MCPyV were 26.5% (nine of 34) and 12.9% (15 of 116). The MCPyV NCCR genotype prevalence in Korean patients was 21.3% (32 of 150) for subtype I and 6% (nine of 150) for subtype IIc. Subtype I, a predominant East Asian strain containing 25 bp tandem repeats, was most common in the MCPyV NCCR data set. Our results confirm that coinfection with other tumor-associated viruses is not associated with NSCLC. Although the role of NCCR rearrangements in MCPyV infection remains unknown, future studies are warranted to determine the associations of MCPyV NCCR sequence rearrangements with specific diseases.
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Affiliation(s)
- Hyoung-Tae Jin
- Ilsong Institute of Life Science, Hallym University, Yeongdeungpo-gu, Seoul, South Korea
| | - Yong-Sun Kim
- Ilsong Institute of Life Science, Hallym University, Yeongdeungpo-gu, Seoul, South Korea
- Department of Microbiology, College of Medicine, Hallym University, Chuncheon, Gangwon-do, South Korea
| | - Eun-Kyoung Choi
- Ilsong Institute of Life Science, Hallym University, Yeongdeungpo-gu, Seoul, South Korea
- Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do, South Korea
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Drokow EK, Effah CY, Agboyibor C, Budu JT, Arboh F, Kyei-Baffour PA, Xiao Y, Zhang F, Wu IXY. Microbial infections as potential risk factors for lung cancer: Investigating the role of human papillomavirus and chlamydia pneumoniae. AIMS Public Health 2023; 10:627-646. [PMID: 37842273 PMCID: PMC10567973 DOI: 10.3934/publichealth.2023044] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 06/22/2023] [Accepted: 07/03/2023] [Indexed: 10/17/2023] Open
Abstract
Background Lung cancer is the leading cause of cancer morbidity and mortality worldwide. Apart from tobacco smoke and dietary factors, microbial infections have been reported as the third leading cause of cancers globally. Deciphering the association between microbiome and lung cancer will provide potential biomarkers and novel insight in lung cancer progression. In this current study, we performed a meta-analysis to decipher the possible association between C. pneumoniae and human papillomavirus (HPV) and the risk of lung cancer. Methods Literature search was conducted in most English and Chinese databases. Data were analyzed using CMA v.3.0 and RevMan v.5.3 software (Cochrane-Mantel-Haenszel method) by random-effects (DerSimonian and Laird) model. Results The overall pooled estimates for HPV studies revealed that HPV infections in patients with lung cancer were significantly higher than those in the control group (OR = 2.33, 95% CI = 1.57-3.37, p < 0.001). Base on subgroup analysis, HPV infection rate was significantly higher in Asians (OR = 6.38, 95% CI = 2.33-17.46, p < 0.001), in tissues (OR = 5.04, 95% CI = 2.27-11.19, p < 0.001) and blood samples (OR = 1.40, 95% CI = 1.02-1.93, p = 0.04) of lung cancer patients but non-significantly lower in males (OR = 0.84, 95% CI = 0.57-1.22, p =0.35) and among lung cancer patients at clinical stage I-II (OR = 0.95, 95% CI = 0.61-1.49, p = 0.82). The overall pooled estimates from C. pneumoniae studies revealed that C. pneumoniae infection is a risk factor among lung cancer patients who are IgA seropositive (OR = 1.88, 95% CI = 1.30-2.70, p < 0.001) and IgG seropositive (OR = 1.50, 95% CI = 1.10-2.04, p = 0.010). All seronegative IgA (OR = 0.69, 95% CI = 0.42-1.16, p = 0.16) and IgG (OR = 0.66, 95% CI = 0.42-105, p = 0.08) titers are not associative risk factors to lung cancer. Conclusions Immunoglobulin (IgA) and IgG seropositive titers of C. pneumoniae and lungs infected with HPV types 16 and 18 are potential risk factors associated with lung cancer.
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Affiliation(s)
- Emmanuel Kwateng Drokow
- Hunan Provinical Key Laboratory of Clinical Epidemiology, Central South University, Changsha 410083, Hunan, China
- Department of Epidemiology and Biostatistics, Xiangya School of Public Health, Central South University, Changsha 410083, Hunan, China
| | - Clement Yaw Effah
- General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou 450003, China
| | - Clement Agboyibor
- School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China
| | | | - Francisca Arboh
- Department of Health Policy and Management, School of Management, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013 Jiangsu Province, China
| | | | - Yao Xiao
- University of Ghana Medical Center, Accra, Ghana
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Fan Zhang
- Department of Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan, China, 410008
| | - Irene XY Wu
- Hunan Provinical Key Laboratory of Clinical Epidemiology, Central South University, Changsha 410083, Hunan, China
- Department of Epidemiology and Biostatistics, Xiangya School of Public Health, Central South University, Changsha 410083, Hunan, China
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Karnosky J, Dietmaier W, Knuettel H, Freigang V, Koch M, Koll F, Zeman F, Schulz C. HPV and lung cancer: A systematic review and meta-analysis. Cancer Rep (Hoboken) 2021; 4:e1350. [PMID: 33624444 PMCID: PMC8388180 DOI: 10.1002/cnr2.1350] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 01/15/2021] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Lung cancer has emerged as a global public health problem and is the most common cause of cancer deaths by absolute cases globally. Besides tobacco, smoke infectious diseases such as human papillomavirus (HPV) might be involved in the pathogenesis of lung cancer. However, data are inconsistent due to differences in study design and HPV detection methods. AIM A systematic meta-analysis was performed to examine the presence of HPV-infection with lung cancer. METHODS AND RESULTS All studies in all languages were considered for the search concepts "lung cancer" and "HPV" if data specific to HPV prevalence in lung cancer tissue were given. This included Journal articles as well as abstracts and conference reports. As detection method, only HPV PCR results from fresh frozen and paraffin-embedded tissue were included. Five bibliographic databases and three registers of clinical trials including MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov were searched through February 2020. A total 4298 publications were identified, and 78 publications were selected, resulting in 9385 included lung cancer patients. A meta-analysis of 15 case-control studies with n = 2504 patients showed a weighted overall prevalence difference of 22% (95% CI: 12%-33%; P < .001) and a weighted overall 4.7-fold (95% CI: 2.7-8.4; P < .001) increase of HPV prevalence in lung cancer patients compared to controls. Overall, HPV prevalence amounted to 13.5% being highest in Asia (16.6%), followed by America (12.8%), and Europe (7.0%). A higher HPV prevalence was found in squamous cell carcinoma (17.9%) compared to adenocarcinoma (P < .01) with significant differences in geographic patterns. HPV genotypes 16 and 18 were the most prevalent high-risk genotypes identified. CONCLUSION In conclusion, our review provides convincing evidence that HPV infection increases the risk of developing lung cancer.
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Affiliation(s)
- Julia Karnosky
- Klinik und Poliklinik für Innere Medizin II, Bereich PneumologieKlinikum der Universität RegensburgRegensburgGermany
| | | | - Helge Knuettel
- UniversitätsbibliothekUniversität RegensburgRegensburgGermany
| | - Viola Freigang
- Klinik und Poliklinik für UnfallchirurgieKlinikum der Universität RegensburgRegensburgGermany
| | - Myriam Koch
- Klinik und Poliklinik für Innere Medizin II, Bereich PneumologieKlinikum der Universität RegensburgRegensburgGermany
| | - Franziska Koll
- Klinik und Poliklinik für Innere Medizin II, Bereich PneumologieKlinikum der Universität RegensburgRegensburgGermany
| | - Florian Zeman
- Zentrum für Klinische StudienKlinikum der Universität RegensburgRegensburgGermany
| | - Christian Schulz
- Klinik und Poliklinik für Innere Medizin II, Bereich PneumologieKlinikum der Universität RegensburgRegensburgGermany
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Mohan A, Agarwal S, Clauss M, Britt NS, Dhillon NK. Extracellular vesicles: novel communicators in lung diseases. Respir Res 2020; 21:175. [PMID: 32641036 PMCID: PMC7341477 DOI: 10.1186/s12931-020-01423-y] [Citation(s) in RCA: 98] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Accepted: 06/15/2020] [Indexed: 02/06/2023] Open
Abstract
The lung is the organ with the highest vascular density in the human body. It is therefore perceivable that the endothelium of the lung contributes significantly to the circulation of extracellular vesicles (EVs), which include exosomes, microvesicles, and apoptotic bodies. In addition to the endothelium, EVs may arise from alveolar macrophages, fibroblasts and epithelial cells. Because EVs harbor cargo molecules, such as miRNA, mRNA, and proteins, these intercellular communicators provide important insight into the health and disease condition of donor cells and may serve as useful biomarkers of lung disease processes. This comprehensive review focuses on what is currently known about the role of EVs as markers and mediators of lung pathologies including COPD, pulmonary hypertension, asthma, lung cancer and ALI/ARDS. We also explore the role EVs can potentially serve as therapeutics for these lung diseases when released from healthy progenitor cells, such as mesenchymal stem cells.
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Affiliation(s)
- Aradhana Mohan
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Kansas Medical Center, Mail Stop 3007, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA
| | - Stuti Agarwal
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Kansas Medical Center, Mail Stop 3007, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA
| | - Matthias Clauss
- Division of Pulmonary, Critical Care, Sleep & Occupational Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Nicholas S Britt
- Department of Pharmacy Practice, University of Kansas School of Pharmacy, Lawrence, Kansas, USA.,Division of Infectious Diseases, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Navneet K Dhillon
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Kansas Medical Center, Mail Stop 3007, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA. .,Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA.
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Weng CF, Chen LJ, Lin CW, Chen HM, Lee HHC, Ling TY, Hsiao FY. Association between the risk of lung cancer and influenza: A population-based nested case-control study. Int J Infect Dis 2019; 88:8-13. [PMID: 31374345 DOI: 10.1016/j.ijid.2019.07.030] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Revised: 07/24/2019] [Accepted: 07/24/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Previous animal studies have shown that certain respiratory oncoviruses can lead to tumorigenesis, especially influenza virus. However, no clinical studies other than animal studies have been conducted to test this hypothesis. OBJECTIVE To investigate the association between influenza and the risk of lung cancer using the Taiwan Cancer Registry Database (TCRD) and Taiwan's National Health Insurance Research Database (NHIRD). METHODS We identified a study cohort consisting of patients aged 40 years or above who were enrolled in the NHIRD between 1 January 2012 and 31 December 2014. Among them, we identified patients with lung cancer (cases) and their matched controls (matched by age, sex, and disease risk score (DRS) at a ratio of 1:10). Multivariate conditional logistic regression models were used to evaluate the association between exposure to influenza (timing and cumulative number) and risk of lung cancer. RESULTS We identified 32,063 cases and 320,627 matched controls. Influenza was associated with a 1.09-fold increased risk of lung cancer (aOR 1.09, 95% CI 1.04-1.14, p<0.0001). The risk of lung cancer increased slightly with cumulative exposure to influenza (1-2 exposures: aOR 1.05, 95% CI 1.00-1.11; 3-4 exposures: aOR 1.12, 95% CI 1.00-1.25; 5+ exposures: aOR 1.25, 95% CI 1.13-1.39). CONCLUSION Exposure to influenza was associated with an increased risk of lung cancer and the risk increased with cumulative exposure to influenza. However, the lack of valid information on smoking could lead to confounding, and future studies collecting patients' smoking histories are warranted to validate the association between influenza and lung cancer.
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Affiliation(s)
- Ching-Fu Weng
- Division of Pulmonary Medicine, Department of Internal Medicine, Hsinchu Cathay General Hospital, Hsinchu, Taiwan; Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Li-Ju Chen
- Health Data Research Center, National Taiwan University, Taipei, Taiwan
| | - Chih-Wan Lin
- Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan
| | - Ho-Min Chen
- Health Data Research Center, National Taiwan University, Taipei, Taiwan
| | - Henry Hsin-Chung Lee
- Department of Surgery, Hsinchu Cathay General Hospital, Hsinchu, Taiwan; Graduate Institute of Translational and Interdisciplinary Medicine, College of Health Sciences and Technology, National Central University, Taoyuan, Taiwan
| | - Thai-Yen Ling
- Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
| | - Fei-Yuan Hsiao
- Graduate Institute of Clinical Pharmacy, National Taiwan University, Taipei, Taiwan; Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; School of Pharmacy, National Taiwan University, Taipei, Taiwan.
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Xiong WM, Xu QP, Li X, Xiao RD, Cai L, He F. The association between human papillomavirus infection and lung cancer: a system review and meta-analysis. Oncotarget 2017; 8:96419-96432. [PMID: 29221217 PMCID: PMC5707111 DOI: 10.18632/oncotarget.21682] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Accepted: 09/21/2017] [Indexed: 12/19/2022] Open
Abstract
To estimate the global attributable fraction of human papillomavirus (HPV) in lung cancer, we provided updated information through a system review and meta-analysis. We did a literature search on PubMed, Ovid and Web of Science to identify case-control studies and cohort studies that detected HPV in lung carcinomas. We included studies that tested 30 or more cases and were published before Feb 28, 2017. We collected information about gender, smoking status, HPV detection methods, HPV types, materials and clinical features. If it was not possible to abstract the required information directly from the papers, we contacted the authors. A meta-analysis was performed to calculate the pooled effect sizes (OR/RR) with 95% confidence intervals (CI) including subgroup analysis and meta-regression to explore sources of heterogeneity, by Stata 13.0 software. 36 case-control studies, contributing data for 6,980 cases of lung cancer and 7,474 controls from 17 countries and one cohort study with 24,162 exposed and 1,026,986 unexposed from China were included. HPV infection was associated with cancer of lung, pooled OR was 3.64 (95% CI: 2.60–5.08), calculated with the random-effects model. Pooled OR for allogeneic case-control studies, self-matched case-control studies and nested case-control studies were 6.71 (95% CI: 4.07–11.07), 2.59 (95% CI: 1.43–4.69) and 0.92 (95% CI: 0.63–1.36), respectively. Pooled OR for HPV 16 and HPV 18 infection, were 3.14 (95% CI: 2.07–4.76) and 2.25 (95% CI: 1.49–3.40), respectively. We also found that HPV infection may be associated with squamous cell carcinoma, adenocarcinoma and small cell carcinoma. There is evidence that HPV infection, especially HPV 16 and HPV 18 infection, significantly increase the risk of lung cancer. Future research needs to focus attention toward whether an HPV vaccine can effectively reduce the incidence of lung cancer.
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Affiliation(s)
- Wei-Min Xiong
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350108, China.,Fujian Provincial Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350108, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350108, China
| | - Qiu-Ping Xu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350108, China.,Fujian Provincial Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350108, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350108, China
| | - Xu Li
- Department of Thoracic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, China
| | - Ren-Dong Xiao
- Department of Thoracic Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350001, China
| | - Lin Cai
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350108, China.,Fujian Provincial Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350108, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350108, China
| | - Fei He
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350108, China.,Fujian Provincial Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, 350108, China.,Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350108, China
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9
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Behdarvand A, Zamani MS, Sadeghi F, Yahyapour Y, Vaziri F, Jamnani FR, Nowruzi B, Fateh A, Siadat SD. Evaluation of Merkel cell polyomavirus in non-small cell lung cancer and adjacent normal cells. Microb Pathog 2017; 108:21-26. [PMID: 28455138 DOI: 10.1016/j.micpath.2017.04.033] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2017] [Revised: 04/22/2017] [Accepted: 04/24/2017] [Indexed: 01/01/2023]
Abstract
Several risk factors have been linked to lung cancer (LC). Nevertheless, a viral etiology has been mentioned for a subset of patients developing LC. The aim of this study was to evaluate the effect of Merkel cell polyomavirus (MCPyV) on developing non-small cell lung cancer (NSCLCs). In total, 96 paraffin-embedded NSCLC biopsies and 96 adjacent non-LC normal specimens were analyzed by quantitative real-time polymerase chain reaction (PCR) for the existence of the MCPyV DNA and the expressions of RNA transcripts. Among the 96 enrolled participants, 42 patients were adenocarcinomas (ADs) and 54 patients were squamous cell carcinoma (SCC). Of the 42 ADs, MCPyV DNA was determined in 15 (35.7%) samples and of the 54 SCC, MCPyV DNA was detected in 22 (40.7%) samples. Only one non-cancerous sample in SCC subjects was positive for MCPyV LT-Ag DNA load (0.216 × 10-3). In MCPyV-positive subjects, the median MCPyV copy number was higher in the patients with ADs (0.016 × 10-3 copies/cell) compared to SCCs (0.005 × 10-3 copies/cell); but this difference was not statistically significant (P = 0.913). In the seven stages of LC, the MCPyV LT-Ag was quantified in stage IV (0.204 × 10-3 copies/cell) more than in other stages. There was statistically significant difference between stages of cancer and MCPyV LT-Ag DNA load (P = 0.002). These results revealed for the first time the presence of MCPyV in a subset of patients with NSCLCs in Iran. Further studies should be carried out to clarify the role of MCPyV in lung carcinogenesis.
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Affiliation(s)
- Anahita Behdarvand
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Mohammad Saber Zamani
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Farzin Sadeghi
- Infectious Diseases & Tropical Medicine Research Center, Babol University of Medical Sciences, Babol, Iran
| | - Yousef Yahyapour
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Farzam Vaziri
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran; Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Fatemeh Rahimi Jamnani
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran; Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
| | - Bahareh Nowruzi
- Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Abolfazl Fateh
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran; Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran.
| | - Seyed Davar Siadat
- Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran; Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran
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10
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Abstract
Recently, an association between Merkel cell polyomavirus (MCPyV) and epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC) was reported. However, the underlying carcinogenic effects and the prognosis related to MCPyV are still unclear. The aim of this study was to clarify the incidence and prognosis related to MCPyV infections in NSCLC.Tissue samples from 167 NSCLC patients (92 with squamous cell carcinomas [SCCs] and 75 with adenocarcinomas) were analyzed for the presence of MCPyV and EGFR mutations. Clinicopathological characteristics, disease-free survival rate, and overall survival rate were assessed with respect to MCPyV.MCPyV DNA was detected in 30 patients (18.0%) out of 167 patients, and EGFR mutations were found in 31 out of 127 patients (24.4%). EGFR mutations were more frequently detected in MCPyV-positive patients than in MCPyV-negative patients; however, this did not reach statistical significance (P = 0.075). There was no difference in overall survival between patients with and without MCPyV infections. The disease-free survival rate of patients with pN0 stage, SCC, or EGFR mutations was lower for patients with MCPyV than without MCPyV (P = 0.036, 0.042, and 0.050, respectively).Although the prevalence of MCPyV infection was relatively low, the presence of MCPyV DNA was significantly correlated with cancer prognosis in subgroups of NSCLC patients. These results suggest that MCPyV may be partly associated with pathogenesis and prognosis in some cases of NSCLC.
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Affiliation(s)
- Gun-Jik Kim
- Department of Thoracic and Cardiovascular Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine
| | - Jae-Ho Lee
- Department of Anatomy, Keimyung University School of Medicine, Dongsan Medical Center, Daegu, Republic of Korea
| | - Deok Heon Lee
- Department of Thoracic and Cardiovascular Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine
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Li M, Zhang XL, Deng F, Qian LT, Meng SP, Shan WL, Wang BL. Involvement of TP53 and TP16 expression in human papillomavirus-associated non-small cell lung cancer. Oncol Lett 2016; 12:3330-3336. [PMID: 27900000 PMCID: PMC5103949 DOI: 10.3892/ol.2016.5087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Accepted: 07/26/2016] [Indexed: 12/29/2022] Open
Abstract
Human papilloma virus (HPV) infection has previously been reported to be associated with TP53 and TP16 expression in Japanese and Taiwanese patients with lung cancer, but data for advanced non-small cell lung cancer (NSCLC) patients is limited. The present study examined the association between HPV infection and TP53 and TP16 expression in Chinese patients with advanced NSCLC. HPV DNA was detected in 20 out of 83 (24%) lung tumors, and was observed more frequently in non-smokers, patients with lymph node metastasis, and patients with poorly differentiated tumors (P=0.048, P=0.044 and P=0.024, respectively). Thirteen (65%) out of 20 HPV-infected tumors were positive for TP53 expression while eight (40%) were positive for TP16 expression. Multivariate analysis revealed that poor differentiation alone (OR=0.163) was an independent predictive factor of HPV infection in NSCLC. TP16-positive patients had a significantly longer survival time when compared with TP16-negative patients (P<0.001, log-rank test), a trend a not observed for TP53. Our results suggest that TP53 and TP16 protein expression is not associated with the expression of HPV DNA, but that TP16 expression may be an independent prognostic factor of long survival in advanced NSCLC.
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Affiliation(s)
- Ming Li
- Department of Clinical Laboratory, Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui 230001, P.R. China; Department of Clinical Laboratory, Anhui Provincial Cancer Hospital, Hefei, Anhui 230031, P.R. China
| | - Xiao-Lei Zhang
- Department of Clinical Laboratory, Anhui Provincial Cancer Hospital, Hefei, Anhui 230031, P.R. China
| | - Fang Deng
- Department of Clinical Laboratory, Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui 230001, P.R. China; Department of Clinical Laboratory, Anhui Provincial Cancer Hospital, Hefei, Anhui 230031, P.R. China
| | - Li-Ting Qian
- Department of Clinical Laboratory, Anhui Provincial Cancer Hospital, Hefei, Anhui 230031, P.R. China
| | - Shui-Ping Meng
- Department of Respiratory Oncology, Anhui Provincial Cancer Hospital, Hefei, Anhui 230031, P.R. China
| | - Wu-Lin Shan
- Department of Clinical Laboratory, Anhui Provincial Cancer Hospital, Hefei, Anhui 230031, P.R. China
| | - Bao-Long Wang
- Department of Clinical Laboratory, Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui 230001, P.R. China
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Gupta P, Haldar D, Naru J, Dey P, Aggarwal AN, Minz RW, Aggarwal R. Prevalence of human papillomavirus, Epstein-Barr virus, and cytomegalovirus in fine needle aspirates from lung carcinoma: A case-control study with review of literature. Diagn Cytopathol 2016; 44:987-993. [PMID: 27774746 DOI: 10.1002/dc.23613] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 07/17/2016] [Accepted: 08/30/2016] [Indexed: 01/10/2023]
Abstract
BACKGROUND Oncogenic viruses have recently been allied with lung carcinoma, however, the causal association has not been established till date. The study was conducted to determine the prevalence of high-risk Human papillomavirus (HPV; subtypes 16, 18, 31, 33 and 45), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) in lung carcinoma using polymerase chain reaction (PCR) on fine needle aspirates. METHODS Fine needle aspirates of patients with lung carcinoma were included as cases. The control samples included normal lung tissue, collected at the time of medico legal autopsies. DNA was extracted from samples of both cases and controls and analysed by PCR for the presence of HPV, EBV and CMV. RESULTS A total of 5/73 (6.8%) cases demonstrated the presence of HPV. Of these, 3 were positive for HPV-16 and one each for HPV-18 and HPV-45. A significant association of HPV with squamous cell carcinoma (SCC) (P = 0.01) was observed. Two cases were positive for EBV; however, the difference was not statistically significant for EBV (P = 0.5) as well as CMV. None of the controls were positive for HPV, EBV or CMV. CONCLUSION We conclude that fine needle aspirates can serve as reliable sample for PCR based detection of viruses. A significantly higher prevalence of HPV in lung cancer and a significant association with SCC was observed, thereby, indicating a positive link between HPV and etiopathogenesis of lung carcinoma. Diagn. Cytopathol. 2016;44:987-993. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Parikshaa Gupta
- Department of Immunopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Dipanjan Haldar
- Department of Cytology and Gynaecologic Pathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Jasmine Naru
- Department of Immunopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Pranab Dey
- Department of Cytology and Gynaecologic Pathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Ashutosh Nath Aggarwal
- Department of Pulmonary Medicine, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Ranjana Walker Minz
- Department of Immunopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Ritu Aggarwal
- Department of Immunopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
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13
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Visalli G, Currò M, Facciolà A, Riso R, Mondello P, Laganà P, Di Pietro A, Picerno I, Spataro P. Prevalence of human papillomavirus in saliva of women with HPV genital lesions. Infect Agent Cancer 2016; 11:48. [PMID: 27570540 PMCID: PMC5000464 DOI: 10.1186/s13027-016-0096-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Accepted: 07/26/2016] [Indexed: 11/18/2022] Open
Abstract
Background The human papilloma viruses (HPVs) are DNA viruses associated with benign and malignant lesions of skin and mucous membranes. The HPVs has been implicated as the cause of virtually all cervical cancers worldwide but studies showed that these viruses can cause numerous cancers in several tissues including Oral Squamous Cell Carcinoma (OSCC). At least 90 % of HPV-positive OSCCs are associated with high-risk (or oncogenic) HPV-16 and oral infection confers an approximate 50-fold increase in risk for HPV-positive OSCC. HPV-positive OSCCs are associated with sexual behaviors in contrast to HPV-negative OSCCs that are associated with chronic tobacco and alcohol use. The aim of this study was to estimate the prevalence of HPV-DNA in saliva samples collected from women in which it has been previously established the HPV infection of the cervix with relative genotyping and, then, to study the possible correlation. Methods Saliva samples were collected from 100 women with HPV cervical lesions, aged between 22 and 52 years old, and 25 healthy women with normal cytology (control group), aged between 20 and 49 years old. PCR assay was used to detect HPV DNA. Results The prevalence of oral HPV infection in saliva samples was 24 % in women with HPV cervical lesions while in the control group was 8 %. It has been demonstrated a strong association between high grade squamous intraepithelial lesion and oral infection due to HPV16 and 18, that are the most frequently detected HPV genotypes. Conclusion This study shows that patients with genital HPV infection are at risk for oral infection and, consequently, for the development of OSCC.
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Affiliation(s)
- Giuseppa Visalli
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via C. Valeria, Gazzi, 98100 Messina, Italy
| | - Monica Currò
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via C. Valeria, Gazzi, 98100 Messina, Italy
| | - Alessio Facciolà
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via C. Valeria, Gazzi, 98100 Messina, Italy
| | - Romana Riso
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via C. Valeria, Gazzi, 98100 Messina, Italy
| | | | - Pasqualina Laganà
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via C. Valeria, Gazzi, 98100 Messina, Italy
| | - Angela Di Pietro
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via C. Valeria, Gazzi, 98100 Messina, Italy
| | - Isa Picerno
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via C. Valeria, Gazzi, 98100 Messina, Italy
| | - Pasquale Spataro
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Via C. Valeria, Gazzi, 98100 Messina, Italy
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Bae JM, Kim EH. Human papillomavirus infection and risk of lung cancer in never-smokers and women: an 'adaptive' meta-analysis. Epidemiol Health 2015; 37:e2015052. [PMID: 26602770 PMCID: PMC4722221 DOI: 10.4178/epih/e2015052] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2015] [Accepted: 11/17/2015] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVES: The incidence of lung cancer in Koreans is increasing in women and in both men and women with a never-smoking history. Human papillomavirus (HPV) infection has been suggested as a modifiable risk factor of lung cancer in never-smokers and women (LCNSW). This systematic review (SR) aimed to evaluate an association between HPV infection and lung cancer risk in LCNSW. METHODS: Based on a prior SR and some expert reviews, we identified refereed, cited, or related articles using the PubMed and Scopus databases. All case-control studies that reported the odds ratio of HPV infection in LCNSW were selected. An estimate of the summary odds ratio (SOR) with 95% confidence intervals (CI) was calculated. RESULTS: A total of four case-control studies were included. The fixed-effect model was applied because of homogeneity (I-squared=0.0%). The SORs in women and in never-smokers were 5.32 (95% CI, 1.75 to 16.17) and 4.78 (2.25 to 10.15) respectively. CONCLUSIONS: These results showed a significant effect of HPV infection in LCNSW. It is evident that developing a preventive plan against LCNSW may be necessary.
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Affiliation(s)
- Jong-Myon Bae
- Department of Preventive Medicine, Jeju National University School of Medicine, Jeju, Korea
| | - Eun Hee Kim
- Department of Preventive Medicine, Jeju National University School of Medicine, Jeju, Korea
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Fan R, Hou WJ, Zhao YJ, Liu SL, Qiu XS, Wang EH, Wu GP. Overexpression of HPV16 E6/E7 mediated HIF-1α upregulation of GLUT1 expression in lung cancer cells. Tumour Biol 2015; 37:4655-63. [PMID: 26508030 DOI: 10.1007/s13277-015-4221-5] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2015] [Accepted: 10/12/2015] [Indexed: 12/19/2022] Open
Abstract
High-risk human papillomavirus (HPV) infection may play an important role in non-small cell lung carcinoma (NSCLC) development. However, some recent studies have proved that it was not directly associated with lung cancer. The aim of this study was to evaluate the underlying molecular mechanism that HPV16 regulate the expression of GLUT1 and may promote the development of lung cancer. HPV16, HIF-1α, and GLUT1 were detected in pleural effusions of patients with lung cancer (n = 95) and with benign lung disease (n = 55) by immunocytochemistry. Western blotting and qRT-PCR were used to detect the expression chances of HPV16 E6/E7, HIF-1α, and GLUT1 in lung cancer cells. HPV16, HIF-1α, and GLUT1 were significantly more likely to be expressed in the malignant group than in the benign group as detected by immunocytochemistry (ICC), and HIF-1α was significantly correlated with HPV16 or GLUT1 in the malignant group (P < 0.01). Expression changes of E6 and E7 significantly promoted the protein expression of HIF-1α, the expression of both protein and mRNA of GLUT1, but had no effect on the expression of HIF-1α mRNA in lung cancer cells. After inhibition of HIF-1α, it obviously downregulated the expression of both protein and mRNA of GLUT1 in lung cancer cells. E6 and E7 regulated the expression of GLUT1 may be due to the mediation of HIF-1α in lung cancer cells. These results suggest that both E6 and E7 play the important role in the regulation of Warburg effect and may be a valuable therapeutic target for HPV-related cancer.
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Affiliation(s)
- Rong Fan
- Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China
| | - Wei-Jian Hou
- Department of Tissue Engineering, College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China
| | - Yu-Jie Zhao
- Center of Biochip, College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China
| | - Shu-Li Liu
- Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China
| | - Xue-Shan Qiu
- Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China
| | - En-Hua Wang
- Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China
| | - Guang-Ping Wu
- Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China.
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16
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Liu X, Zhang H, Su L, Yang P, Xin Z, Zou J, Ren S, Zuo Y. Low expression of dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein in lung cancer and significant correlations with brain metastasis and natural killer cells. Mol Cell Biochem 2015; 407:151-60. [PMID: 26150177 PMCID: PMC7101997 DOI: 10.1007/s11010-015-2465-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2015] [Accepted: 05/29/2015] [Indexed: 11/30/2022]
Abstract
Dendritic cell-specific intercellular adhesion molecule-grabbing nonintegrin-related protein (DC-SIGNR) is a type II transmembrane protein which has been reported to bind a variety of pathogens as well as participate in immunoregulation. But the association between the level of DC-SIGNR and lung cancer is unknown. To investigate the clinical diagnostic significance of DC-SIGNR in lung cancer, we investigated serum DC-SIGNR levels in 173 lung cancer patients and 134 healthy individuals using enzyme-linked immunosorbent assay (ELISA). Results showed that serum DC-SIGNR levels in lung cancer patients were lower than that in healthy controls (P = 0.0003). A cut-off value of 3.8998 ng/L for DC-SIGNR predicted the presence of lung cancer with 78.03% sensitivity and 49.25% specificity (area under the curve = 0.6212, P = 0.0003). Strikingly, serum DC-SIGNR levels were significantly higher in lung cancer patients with brain metastasis compared to those without metastasis (P = 0.0283). Moreover, the serum concentrations of DC-SIGNR in lung cancer patients also correlated significantly with serum natural killer cells percentage (P = 0.0017). In addition, immunohistochemistry assay demonstrated that the expression of DC-SIGNR in lung tissues of 31 lung cancer patients and 13 tuberculosis patients was significantly lower than that in 18 normal lung tissues (P = 0.0418, 0.0289), and there is no significant difference between tuberculosis tissues and lung cancer tissues (P = 0.2696). These results suggest that DC-SIGNR maybe a promising biological molecule that has the potential for clinical research of lung cancer, whereas its underlying roles are needed to be investigated in further studies.
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Affiliation(s)
- Xiaoli Liu
- Department of Clinical Biochemistry, College of Laboratory Diagnostic Medicine, Dalian Medical University, Dalian, 116044, China
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Hartley CP, Steinmetz HB, Memoli VA, Tafe LJ. Small cell neuroendocrine carcinomas of the lung do not harbor high-risk human papillomavirus. Hum Pathol 2015; 46:577-82. [DOI: 10.1016/j.humpath.2014.12.012] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Revised: 12/17/2014] [Accepted: 12/24/2014] [Indexed: 01/06/2023]
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Jalilvand S, Shoja Z, Hamkar R. Human Papillomavirus Burden in Different Cancers in Iran: a Systematic Assessment. Asian Pac J Cancer Prev 2014; 15:7029-35. [DOI: 10.7314/apjcp.2014.15.17.7029] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Zhang E, Feng X, Liu F, Zhang P, Liang J, Tang X. Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells. PLoS One 2014; 9:e103440. [PMID: 25058399 PMCID: PMC4110025 DOI: 10.1371/journal.pone.0103440] [Citation(s) in RCA: 82] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Accepted: 07/02/2014] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Human papillomavirus (HPV)-16 infection may be related to non-smoking associated lung cancer. Our previous studies have found that HPV-16 oncoproteins promoted angiogenesis via enhancing hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) expression in non-small cell lung cancer (NSCLC) cells. In this study, we further investigated the roles of PI3K/Akt and c-Jun signaling pathways in it. METHODS Human NSCLC cell lines, A549 and NCI-H460, were stably transfected with pEGFP-16 E6 or E7 plasmids. Western blotting was performed to analyze the expression of HIF-1α, p-Akt, p-P70S6K, p-P85S6K, p-mTOR, p-JNK, and p-c-Jun proteins. VEGF and IL-8 protein secretion and mRNA levels were determined by ELISA and Real-time PCR, respectively. The in vitro angiogenesis was observed by human umbilical vein endothelial cells (HUVECs) tube formation assay. Co-immunoprecipitation was performed to analyze the interaction between c-Jun and HIF-1α. RESULTS HPV-16 E6 and E7 oncoproteins promoted the activation of Akt, P70S6K, P85S6K, mTOR, JNK, and c-Jun. LY294002, a PI3K inhibitor, inhibited HPV-16 oncoprotein-induced activation of Akt, P70S6K, and P85S6K, expression of HIF-1α, VEGF, and IL-8, and in vitro angiogenesis. c-Jun knockdown by specific siRNA abolished HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Additionally, HPV-16 oncoproteins promoted HIF-1α protein stability via blocking proteasome degradation pathway, but c-Jun knockdown abrogated this effect. Furthermore, HPV-16 oncoproteins increased the quantity of c-Jun binding to HIF-1α. CONCLUSIONS PI3K/Akt signaling pathway and c-Jun are involved in HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Moreover, HPV-16 oncoproteins promoted HIF-1α protein stability possibly through enhancing the interaction between c-Jun and HIF-1α, thus making a contribution to angiogenesis in NSCLC cells.
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MESH Headings
- Carcinoma, Non-Small-Cell Lung/blood supply
- Carcinoma, Non-Small-Cell Lung/metabolism
- Carcinoma, Non-Small-Cell Lung/virology
- Cell Line, Tumor
- Chromones/pharmacology
- Genes, jun/drug effects
- Humans
- Hypoxia-Inducible Factor 1, alpha Subunit
- In Vitro Techniques
- Interleukin-8/metabolism
- Lung Neoplasms/blood supply
- Lung Neoplasms/metabolism
- Lung Neoplasms/virology
- MAP Kinase Signaling System/drug effects
- Morpholines/pharmacology
- Neovascularization, Pathologic/metabolism
- Neovascularization, Pathologic/virology
- Oncogene Proteins, Viral/genetics
- Oncogene Proteins, Viral/metabolism
- Papillomavirus E7 Proteins/genetics
- Papillomavirus E7 Proteins/metabolism
- Repressor Proteins/genetics
- Repressor Proteins/metabolism
- Vascular Endothelial Growth Factor A
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Affiliation(s)
- Erying Zhang
- Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong, China
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical College, Zhanjiang, Guangdong, China
| | - Xiaowei Feng
- Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong, China
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical College, Zhanjiang, Guangdong, China
| | - Fei Liu
- Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong, China
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical College, Zhanjiang, Guangdong, China
| | - Peihua Zhang
- Institute of Plastic Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China
| | - Jie Liang
- Institute of Plastic Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong, China
| | - Xudong Tang
- Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong, China
- Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical College, Zhanjiang, Guangdong, China
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Sagerup CMT, Nymoen DA, Halvorsen AR, Lund-Iversen M, Helland A, Brustugun OT. Human papilloma virus detection and typing in 334 lung cancer patients. Acta Oncol 2014; 53:952-7. [PMID: 24446743 DOI: 10.3109/0284186x.2013.879608] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Unlike cervical, anogenital and oropharyngeal cancers, where high-risk human papillomavirus (hrHPV) has long been known to play a major role, a causative link between HPV and lung cancer has been investigated for decades with discrepant results. METHODS Lung cancer patients eligible for surgical treatment were tested for the presence of HPV-DNA in excised, fresh frozen lung tumor tissue. Patients that tested positive were further examined for the presence of HPV-DNA in adjacent normal lung parenchyma. HPV detection and genotyping was performed using a polymerase chain reaction (PCR)-based approach and allowed the typing of 13 "high-risk"-HPV-types and 2 "low-risk"-HPV-types. RESULTS Of the 334 tumor-DNA samples tested, 13 (3.9%) showed presence of HPV-DNA, of which 12 were of a high-risk HPV type (16, 33, 66). In those tested positive, HPV-DNA was not found in adjacent normal lung tissue. No correlation with smoking or EGFR/KRAS mutation status was seen, and only one of 84 squamous cell carcinomas was HPV-positive. CONCLUSION We conclude that HPV is rarely associated with lung cancer in a Northern European population and in those tested positive, more functional studies are required to determine the role HPV plays in lung cancer oncogenesis.
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Affiliation(s)
- Camilla M T Sagerup
- Department of Oncology, Oslo University Hospital, The Norwegian Radium Hospital , Oslo , Norway
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21
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Al-Shabanah OA, Hafez MM, Hassan ZK, Sayed-Ahmed MM, Abozeed WN, Al-Rejaie SS, Alsheikh AA. Human papillomavirus genotyping and integration in ovarian cancer Saudi patients. Virol J 2013; 10:343. [PMID: 24252426 PMCID: PMC3842654 DOI: 10.1186/1743-422x-10-343] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Accepted: 11/08/2013] [Indexed: 01/23/2023] Open
Abstract
Background Human papillomavirus (HPV) is associated with different malignancies but its role in the pathogenesis of ovarian cancer is controversial. This study investigated the prevalence, genotyping and physical state of HPV in ovarian cancer Saudi patients. Methods Hundred formalin fixed paraffin embedded (FFPE) ovarian carcinoma tissues and their normal adjacent tissues (NAT) were included in the study. HPV was detected by nested polymerase chain reaction (PCR) using degenerated HPVL1 consensus primer pairs MY09/MY11 and GP5+/GP6 + to amplify a broad spectrum of HPV genotypes in a single reaction. The HPV positive samples were further genotyped using DNA sequencing. The physical state of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT) assay in the samples positive for HPV16 and/or HPV18. Results High percentage of HPV (42%) was observed in ovarian carcinoma compared to 8% in the NAT. The high-risk HPV types 16, 18 and 45 were highly associated with the advanced stages of tumor, while low-risk types 6 and 11 were present in NAT. In malignant tissues, HPV-16 was the most predominant genotype followed by HPV-18 and -45. The percentage of viral integration into the host genome was significantly high (61.1%) compared to 38.9% episomal in HPV positive tumors tissues. In HPV18 genotype the percentage of viral integration was 54.5% compared to 45.5% episomal. Conclusion The high risk HPV genotypes in ovarian cancer may indicate its role in ovarian carcinogenesis. The HPV vaccination is highly recommended to reduce this type of cancer.
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Affiliation(s)
| | - Mohamed M Hafez
- Department of pharmacology, College of pharmacy; King Saud University, P,O, Box 2457, Riyadh 11451, Kingdom of Saudi Arabia.
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Kawaguchi T, Ando M, Ito N, Isa SI, Tamiya A, Shimizu S, Saka H, Kubo A, Koh Y, Matsumura A. Rationale and Design of the Japan Molecular Epidemiology for Lung Cancer Study. Clin Lung Cancer 2013; 14:596-600. [DOI: 10.1016/j.cllc.2013.03.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2012] [Revised: 02/26/2013] [Accepted: 03/26/2013] [Indexed: 11/16/2022]
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Mammas IN, Sourvinos G, Spandidos DA. The ‘Trojan horse’ oncogenic strategy of HPVs in childhood. Future Virol 2013. [DOI: 10.2217/fvl.13.57] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
HPVs are considered to be the principal cause of cervical cancer worldwide. During the last decade, their possible oncogenic involvement has also been proposed in a substantial proportion of nongenital cancers, such as breast and lung cancer. The presence of high-risk HPVs in the neonatal oral mucosa supports the transmission of HPVs from the mother to her newborn. This review presents current evidence that supports the perinatal transmission of high-risk HPVs and suggests that this may be the initial step of the oncogenic strategy of high-risk HPVs in humans. The hypothesis that children are a unique reservoir of silent high-risk HPVs, analogously to the Trojan horse, should be investigated further.
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Affiliation(s)
- Ioannis N Mammas
- Department of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Crete, Greece
| | - George Sourvinos
- Department of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Crete, Greece.
| | - Demetrios A Spandidos
- Department of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Crete, Greece
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Alberg AJ, Brock MV, Ford JG, Samet JM, Spivack SD. Epidemiology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143:e1S-e29S. [PMID: 23649439 DOI: 10.1378/chest.12-2345] [Citation(s) in RCA: 481] [Impact Index Per Article: 40.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Ever since a lung cancer epidemic emerged in the mid-1900 s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. METHODS A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. RESULTS Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. CONCLUSIONS Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers.
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Affiliation(s)
- Anthony J Alberg
- Hollings Cancer Center and the Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC.
| | - Malcolm V Brock
- Department of Surgery, School of Medicine, Johns Hopkins University, Baltimore, MD
| | - Jean G Ford
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Jonathan M Samet
- Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA
| | - Simon D Spivack
- Division of Pulmonary Medicine, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
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Jafari H, Gharemohammadlou R, Fakhrjou A, Ebrahimi A, Nejati-Koshki K, Nadri M, Sakhinia E. Genotyping of Human Papillomavirus and TP53 Mutaions at Exons 5 to 7 in Lung Cancer Patients from Iran. BIOIMPACTS : BI 2013; 3:135-40. [PMID: 24163806 DOI: 10.5681/bi.2013.018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 01/13/2013] [Revised: 03/22/2013] [Accepted: 03/24/2013] [Indexed: 11/17/2022]
Abstract
INTRODUCTION There is a powerful relationship between high-risk human papillomaviruses and lung cancer. In fact, inactivation of p53 is the most common genetic abnormality in lung cancer. Indeed, the frequency of HPV types and TP53 mutations in squamous cell carcinoma of lung, among patients from the northwest of Iran has been evaluated in this article. Methodes: Fifty Paraffin embedded blocks of lung SCC were selected for detection of HPV DNA by Nested PCR, and then DNA was sequenced for HPV typing. Equal numbers of positive and negative samples for the HPV DNA were examined for the presence of mutations in exons 5-7 of the TP53 gene by PCR and direct sequencing. RESULTS Overtly 9 (18%) of 50 samples presented the HPV DNA: eight were HPV-18 and one was HPV-6. TP53 mutations were found in 5 samples (27.7%). Of these, 4 cases showed mutations in exon 5 and one case contained a mutation in exon 7.The most frequent mutation in exon 5 was the C to G transversion (c.409C>G), and also the T to A tansversion (c.770T>A) in exon 7. CONCLUSION This study showed that HPV-18 is more likely to conscequence in the development of lung cancer among some communities. Genetic alterations, alongside with environmental factors, all play a significant role in the pathogenesis of lung cancer.
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Affiliation(s)
- Hossein Jafari
- Department of Medical Genetics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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Detection of Immunoglobulin G against E7 of Human Papillomavirus in Non-Small-Cell Lung Cancer. JOURNAL OF ONCOLOGY 2013; 2013:240164. [PMID: 23533408 PMCID: PMC3603668 DOI: 10.1155/2013/240164] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2012] [Revised: 02/04/2013] [Accepted: 02/05/2013] [Indexed: 11/25/2022]
Abstract
Background. A significant number of non-small-cell lung cancers (NSCLC) have human papillomavirus (HPV) DNA integrated in their genome. This study sought to further establish HPV's possible etiologic link to NSCLC by evaluating an immune response to HPV's oncogene, E7, in patients with NSCLC. Patients and Methods. Antibodies (IgG) in serum against E7 for HPV 16 and 18 in 100 patients with NSCLC were examined by enzyme-linked immunosorbent assay (ELISA). Results. Sixteen NSCLC patients were found to have a high titration of IgG for HPV oncogenic E7 protein. 23.5% of adenocarcinomas (AC,) and 15.4% of squamous cell carcinomas (SCC) were positive for IgG against HPV E7. HPV-18 (11%) had a slightly higher frequency than HPV-16 (6%). Of the six positive cases for HPV-16, 3 were AC, 2 SCC, and 1 NOS (not otherwise specified). For the 11 HPV-18 positives, 7 were AC, and 4 SCC. The one case with IgG against HPV 16 and 18 was AC. One case had high cross-reactive levels against E7 of HPV 16 and 18. Two (28%) of 7 patients who reported never smoking were positive for HPV, and 12 (13.6%) of 88 smokers were HPV positive. Conclusions. The study detected high levels of IgG against E7 in 16% of NSCLC patients. This adds evidence to a potential role of HPV in the pathogenesis of NSCLC.
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Detection of Merkel cell polyomavirus with a tumour-specific signature in non-small cell lung cancer. Br J Cancer 2013; 108:629-37. [PMID: 23322199 PMCID: PMC3593539 DOI: 10.1038/bjc.2012.567] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Background: We searched for a viral aetiology for non-small cell lung cancer (NSCLC), focusing on Merkel cell polyomavirus (MCPyV). Methods: We analysed 112 Japanese cases of NSCLC for the presence of the MCPyV genome and the expressions of RNA transcripts and MCPyV-encoded antigen. We also conducted the first analysis of the molecular features of MCPyV in lung cancers. Results: PCR revealed that 9 out of 32 squamous cell carcinomas (SCCs), 9 out of 45 adenocarcinomas (ACs), 1 out of 32 large-cell carcinomas, and 1 out of 3 pleomorphic carcinomas were positive for MCPyV DNA. Some MCPyV DNA-positive cancers expressed large T antigen (LT) RNA transcripts. Immunohistochemistry showed that MCPyV LT antigen was expressed in the tumour cells. The viral integration sites were identified in one SCC and one AC. One had both episomal and integrated/truncated forms. The other carried an integrated MCPyV genome with frameshift mutations in the LT gene. Conclusion: We have demonstrated the expression of a viral oncoprotein, the presence of integrated MCPyV, and a truncated LT gene with a preserved retinoblastoma tumour-suppressor protein-binding domain in NSCLCs. Although the viral prevalence was low, the tumour-specific molecular signatures support the possibility that MCPyV is partly associated with the pathogenesis of NSCLC in a subset of patients.
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Flake C, Arafa J, Hall A, Ence E, Howard K, Kingsley K. Screening and detection of human papillomavirus (HPV) high-risk strains HPV16 and HPV18 in saliva samples from subjects under 18 years old in Nevada: a pilot study. BMC Oral Health 2012; 12:43. [PMID: 23088565 PMCID: PMC3532331 DOI: 10.1186/1472-6831-12-43] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2012] [Accepted: 10/18/2012] [Indexed: 11/21/2022] Open
Abstract
Background Human papillomaviruses (HPV) are oncogenic and mainly associated with cervical cancers. Recent evidence has demonstrated HPV infection in other tissues, including oral epithelia and mucosa. Although a recent pilot study provided new information about oral HPV status in healthy adults from Nevada, no information was obtained about oral HPV prevalence among children or teenagers, therefore, the goal of this study is to provide more detailed information about oral prevalence of high-risk HPV among children and teenagers in Nevada. Methods This retrospective study utilized previously collected saliva samples, obtained from pediatric dental clinic patients (aged 2 – 11) and local school district teenagers (aged 12-17) for high-risk HPV screening (n=118) using qPCR for quantification and confirmation of analytical sensitivity and specificity. Results A small subset of saliva samples were found to harbor high-risk HPV16 (n=2) and HPV18 (n=1), representing a 2.5% of the total. All three were obtained from teenage males, and two of these three samples were from White participants. Conclusions Although this retrospective study could not provide correlations with behavioral or socioeconomic data, this project successfully screened more than one hundred saliva samples for high-risk HPV, confirming both HPV16 and HPV18 strains were present in a small subset. With increasing evidence of oral HPV infection in children, this study provides critical information of significant value to other dental, medical, oral and public health professionals who seek to further an understanding of oral health and disease risk in pediatric populations.
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Affiliation(s)
- Colton Flake
- Department of Advanced Education in Pediatric Dentistry, University of Nevada, Las Vegas - School of Dental Medicine, Las Vegas, NV, USA
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McCarthy WJ, Meza R, Jeon J, Moolgavkar SH. Chapter 6: Lung cancer in never smokers: epidemiology and risk prediction models. RISK ANALYSIS : AN OFFICIAL PUBLICATION OF THE SOCIETY FOR RISK ANALYSIS 2012; 32 Suppl 1:S69-84. [PMID: 22882894 PMCID: PMC3485693 DOI: 10.1111/j.1539-6924.2012.01768.x] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/06/2023]
Abstract
In this chapter we review the epidemiology of lung cancer incidence and mortality among never smokers/nonsmokers and describe the never smoker lung cancer risk models used by the Cancer Intervention and Surveillance Network (CISNET) modelers. Our review focuses on those influences likely to have measurable population impact on never smoker risk, such as secondhand smoke, even though the individual-level impact may be small. Occupational exposures may also contribute importantly to the population attributable risk of lung cancer. We examine the following risk factors in this chapter: age, environmental tobacco smoke, cooking fumes, ionizing radiation including radon gas, inherited genetic susceptibility, selected occupational exposures, preexisting lung disease, and oncogenic viruses. We also compare the prevalence of never smokers between the three CISNET smoking scenarios and present the corresponding lung cancer mortality estimates among never smokers as predicted by a typical CISNET model.
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Affiliation(s)
- William J McCarthy
- Division of Cancer Prevention & Control Research, University of California-Los Angeles, 650 Charles Young Drive, Los Angeles, CA 90095-6900, USA.
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Abstract
Several observations have led us to a new hypothesis for cancer mechanism. First, that cancer appears only on those multicellular organisms with complicated wound-healing capacities. Second, that wounds considered as risk factors can be identified in all cancers in clinics. And finally, that oncogene activation appears not only in cancer, but also in normal physiology and noncancer pathology processes. Our proposed hypothesis is that cancer is a natural wound healing-related process, which includes oncogene activations, cytokine secretions, stem cell recruitment differentiation, and tissue remodeling. Wounds activate oncogenes of some cells and the latter secrete cytokines to recruit stem cells to heal the wounds. However, if the cause of the wound or if the wound persists, such as under the persistent UV and carcinogen exposures, the continuous wound healing process will lead to a clinical cancer mass. There is no system in nature to stop or reverse the wound healing process in the middle stage when the wound exists. The outcome of the cancer mechanism is either healing the wound or exhausting the whole system (death). The logic of this cancer mechanism is consistent with the rationales of the other physiological metabolisms in the body-for survival. This hypothesis helps to understand many cancer mysteries derived from the mutation theory, such as why cancer only exists in a small proportion of multicellular organisms, although they are all under potential mutation risks during DNA replications. The hypothesis can be used to interpret and guide cancer prevention, recurrence, metastasis, in vitro and in vivo studies, and personalized treatments.
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Affiliation(s)
- Xiaolong Meng
- Breast Medical Oncology Department, MD Anderson Cancer Center, 1155 Hermann Pressler Dr., Houston, TX 77030 USA
| | - Jie Zhong
- Neurosurgery Department, MD Anderson Cancer Center, 1400 Holcombe Blvd., Houston, TX 77030 USA
| | - Shuying Liu
- Breast Medical Oncology Department, MD Anderson Cancer Center, 1155 Hermann Pressler Dr., Houston, TX 77030 USA
| | - Mollianne Murray
- Systems Biology Department, MD Anderson Cancer Center, 7435 Fannin St., Houston, TX 77054 USA
| | - Ana M. Gonzalez-Angulo
- Breast Medical Oncology Department, MD Anderson Cancer Center, 1155 Hermann Pressler Dr., Houston, TX 77030 USA
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Malisic E, Jankovic R, Jakovljevic K. Detection and genotyping of human papillomaviruses and their role in the development of ovarian carcinomas. Arch Gynecol Obstet 2012; 286:723-8. [DOI: 10.1007/s00404-012-2367-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2011] [Accepted: 04/24/2012] [Indexed: 11/28/2022]
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Lung MSY, Zhang N, Murray V. Site-directed mutagenesis of human papillomavirus 18 promoter elements and tissue-specific expression in cervical carcinoma cells. Virus Genes 2012; 44:395-402. [DOI: 10.1007/s11262-012-0723-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2011] [Accepted: 01/31/2012] [Indexed: 10/28/2022]
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Yu Y, Yang A, Hu S, Zhang J, Yan H. Significance of human papillomavirus 16/18 infection in association with p53 mutation in lung carcinomas. CLINICAL RESPIRATORY JOURNAL 2012; 7:27-33. [PMID: 22171791 DOI: 10.1111/j.1752-699x.2011.00277.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
INTRODUCTION The role of high-risk human papillomavius (HPV) 16/18 in the development of lung cancer has recently been explored, and p53 mutation is a finding in lung cancer; however, its association with HPV infection is not well studied. OBJECTIVES To investigate HPV 16/18 infection and p53 mutation in lung carcinomas and their association with tumor behavior. METHODS AND RESULTS We expanded our prior study to include 107 squamous cell carcinoma (SCC), 63 adenocarcinoma (AC) and 91 non-cancer control cases of lung from a population of Western China. The results confirmed that HPV infection is more prevalent in SCC (59.8%) comparing with that of AC (17.5%) and the control cases (23.1%) (P<0.001), and genotyping demonstrated predominant HPV 16/18 infection in the carcinomas and HPV 6 in the control cases. By immunohistochemistry, p53 mutation was detected in 67.3% of SCC and 60.3% of AC, in comparison with 9.9% in the control (P<0.001). Within the group of SCC, the p53 mutation rate is significantly higher in those with HPV infection (78.1%) than that of the non-infected carcinomas (51.2%, P=0.004). However, this difference is not proven to be significant in the groups of AC and the controls. Clinicopathological analysis demonstrated that the coexistence of p53 mutation and HPV infection was associated with lymph node metastasis (P=0.001) and high-clinical TNM stage of SCC (P=0.001). As there was no sequencing data, the evidence for HPV 16/18 E6 induced p53 mutation is still indirect. CONCLUSION This study indicates that p53 mutation and HPV 16/18 infection might coordinate in the development of lung squamous cell carcinomas, and their coexistence is associated with poor prognosis.
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Affiliation(s)
- Yan Yu
- Department of Public Health, Xi'an Jiaotong University School of Medicine, Xi'an, Shanxi, China
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Restrepo CS, Chen MM, Martinez-Jimenez S, Carrillo J, Restrepo C. Chest neoplasms with infectious etiologies. World J Radiol 2011; 3:279-88. [PMID: 22224176 PMCID: PMC3251813 DOI: 10.4329/wjr.v3.i12.279] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2011] [Revised: 09/19/2011] [Accepted: 10/11/2011] [Indexed: 02/06/2023] Open
Abstract
A wide spectrum of thoracic tumors have known or suspected viral etiologies. Oncogenic viruses can be classified by the type of genomic material they contain. Neoplastic conditions found to have viral etiologies include post-transplant lymphoproliferative disease, lymphoid granulomatosis, Kaposi’s sarcoma, Castleman’s disease, recurrent respiratory papillomatosis, lung cancer, malignant mesothelioma, leukemia and lymphomas. Viruses involved in these conditions include Epstein-Barr virus, human herpes virus 8, human papillomavirus, Simian virus 40, human immunodeficiency virus, and Human T-lymphotropic virus. Imaging findings, epidemiology and mechanism of transmission for these diseases are reviewed in detail to gain a more thorough appreciation of disease pathophysiology for the chest radiologist.
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Dela Cruz CS, Tanoue LT, Matthay RA. Lung cancer: epidemiology, etiology, and prevention. Clin Chest Med 2011. [PMID: 22054876 DOI: 10.1016/j.ccm.2011.09.001.lung] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Lung cancer is the leading cause of cancer death in the United States and around the world. A vast majority of lung cancer deaths are attributable to cigarette smoking, and curbing the rates of cigarette smoking is imperative. Understanding the epidemiology and causal factors of lung cancer can provide additional foundation for disease prevention. This article focuses on modifiable risk factors, including tobacco smoking, occupational carcinogens, diet, and ionizing radiation. It also discusses briefly the molecular and genetic aspects of lung carcinogenesis.
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Affiliation(s)
- Charles S Dela Cruz
- Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, TAC S441-C, New Haven, CT 06519, USA.
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Abstract
Lung cancer is the leading cause of cancer death in the United States and around the world. A vast majority of lung cancer deaths are attributable to cigarette smoking, and curbing the rates of cigarette smoking is imperative. Understanding the epidemiology and causal factors of lung cancer can provide additional foundation for disease prevention. This article focuses on modifiable risk factors, including tobacco smoking, occupational carcinogens, diet, and ionizing radiation. It also discusses briefly the molecular and genetic aspects of lung carcinogenesis.
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Affiliation(s)
- Charles S Dela Cruz
- Pulmonary and Critical Care Medicine Section, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, TAC S441-C, New Haven, CT 06519, USA.
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Carpagnano GE, Koutelou A, Natalicchio MI, Martinelli D, Ruggieri C, Di Taranto A, Antonetti R, Carpagnano F, Foschino-Barbaro MP. HPV in exhaled breath condensate of lung cancer patients. Br J Cancer 2011; 105:1183-90. [PMID: 21952627 PMCID: PMC3208494 DOI: 10.1038/bjc.2011.354] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2011] [Revised: 08/02/2011] [Accepted: 08/04/2011] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND A recent intriguing carcinogenetic hypothesis for lung cancer foresees its viral aetiology. The human papilloma virus (HPV) is the main virus actually recognised in the pathogenesis of lung cancer. The aim of this study was to investigate, for the first time to our knowledge, the presence of HPV in the exhaled breath condensate (EBC) of lung cancer patients. MATERIALS AND METHOD We enrolled 89 patients affected by lung cancer and 68 controls. HPV infections were investigated in their EBC, paired bronchial brushing and neoplastic lung tissue through genotyping. RESULTS We were able to detect HPV in the EBC, bronchial brushing and neoplastic lung tissue. We described the presence of an HPV infection in 16.4% of the subjects affected by non-small cell lung cancer, but in none of the controls. HPV 16 and 31 turned out to be the most widespread genotypes. The HPV positivity in airways as well as in the smoking habit was seen to independently increase the individual's susceptibility to developing lung cancer. CONCLUSION When summing up, we demonstrated the possibility to identify an HPV infection in the EBC of lung cancer patients; further, we supported the notion that the EBC is a suitable tool to study airway colonisation. That being said, although further studies are needed to confirm our results, we retain the study of HPV in EBC to be very interesting in terms of future programmes involving lung-cancer screening.
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Affiliation(s)
- G E Carpagnano
- Institute of Respiratory Disease, Department of Medical and Occupational Sciences, Faculty of Medicine, University of Foggia, Foggia, Italy.
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Turner DO, Williams-Cocks SJ, Bullen R, Catmull J, Falk J, Martin D, Mauer J, Barber AE, Wang RC, Gerstenberger SL, Kingsley K. High-risk human papillomavirus (HPV) screening and detection in healthy patient saliva samples: a pilot study. BMC Oral Health 2011; 11:28. [PMID: 21985030 PMCID: PMC3200164 DOI: 10.1186/1472-6831-11-28] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2010] [Accepted: 10/10/2011] [Indexed: 11/10/2022] Open
Abstract
Background The human papillomaviruses (HPV) are a large family of non-enveloped DNA viruses, mainly associated with cervical cancers. Recent epidemiologic evidence has suggested that HPV may be an independent risk factor for oropharyngeal cancers. Evidence now suggests HPV may modulate the malignancy process in some tobacco- and alcohol-induced oropharynx tumors, but might also be the primary oncogenic factor for inducing carcinogenesis among some non-smokers. More evidence, however, is needed regarding oral HPV prevalence among healthy adults to estimate risk. The goal of this study was to perform an HPV screening of normal healthy adults to assess oral HPV prevalence. Methods Healthy adult patients at a US dental school were selected to participate in this pilot study. DNA was isolated from saliva samples and screened for high-risk HPV strains HPV16 and HPV18 and further processed using qPCR for quantification and to confirm analytical sensitivity and specificity. Results Chi-square analysis revealed the patient sample was representative of the general clinic population with respect to gender, race and age (p < 0.05). Four patient samples were found to harbor HPV16 DNA, representing 2.6% of the total (n = 151). Three of the four HPV16-positive samples were from patients under 65 years of age and all four were female and Hispanic (non-White). No samples tested positive for HPV18. Conclusions The successful recruitment and screening of healthy adult patients revealed HPV16, but not HPV18, was present in a small subset. These results provide new information about oral HPV status, which may help to contextualize results from other studies that demonstrate oral cancer rates have risen in the US among both females and minorities and in some geographic areas that are not solely explained by rates of tobacco and alcohol use. The results of this study may be of significant value to further our understanding of oral health and disease risk, as well as to help design future studies exploring the role of other factors that influence oral HPV exposure, as well as the short- and long-term consequences of oral HPV infection.
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Affiliation(s)
- Deidre O Turner
- University of Nevada, Las Vegas - School of Community Health Sciences, Department of Environmental and Occupational Health, Las Vegas, Nevada, USA
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Hamedi. Surface Electromyography-Based Facial Expression Recognition in Bi-Polar Configuration. ACTA ACUST UNITED AC 2011. [DOI: 10.3844/jcssp.2011.1407.1415] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Abstract
Malignancies account for more than a third of all deaths in human immunodeficiency virus (HIV)-positive patients. Although acquired immunodeficiency syndrome-related mortality is decreasing with the introduction of effective antiretroviral therapy, the incidence of lung cancer in patients with HIV remains high. Lung cancer has now become the leading cause of mortality among the nonacquired immunodeficiency syndrome defining malignancies. Within the HIV population, the incidence of lung cancer is estimated to be approximately 2 to 4 times that of the general population. Often these patients present with advanced disease (stage III or IV) at a younger age and have an inferior overall survival, when compared with non-HIV patients. Development of lung cancer in patients with HIV has been linked to various factors including immunosuppression, CD4 count, viral load, and smoking. This article reviews the impact of HIV on the incidence, risk factors, clinical presentation, and treatment of lung cancer.
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Buonomo T, Carraresi L, Rossini M, Martinelli R. Involvement of aryl hydrocarbon receptor signaling in the development of small cell lung cancer induced by HPV E6/E7 oncoproteins. J Transl Med 2011; 9:2. [PMID: 21205295 PMCID: PMC3022727 DOI: 10.1186/1479-5876-9-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2010] [Accepted: 01/04/2011] [Indexed: 12/30/2022] Open
Abstract
Background Lung cancers consist of four major types that and for clinical-pathological reasons are often divided into two broad categories: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). All major histological types of lung cancer are associated with smoking, although the association is stronger for SCLC and squamous cell carcinoma than adenocarcinoma. To date, epidemiological studies have identified several environmental, genetic, hormonal and viral factors associated with lung cancer risk. It has been estimated that 15-25% of human cancers may have a viral etiology. The human papillomavirus (HPV) is a proven cause of most human cervical cancers, and might have a role in other malignancies including vulva, skin, oesophagus, head and neck cancer. HPV has also been speculated to have a role in the pathogenesis of lung cancer. To validate the hypothesis of HPV involvement in small cell lung cancer pathogenesis we performed a gene expression profile of transgenic mouse model of SCLC induced by HPV-16 E6/E7 oncoproteins. Methods Gene expression profile of SCLC has been performed using Agilent whole mouse genome (4 × 44k) representing ~ 41000 genes and mouse transcripts. Samples were obtained from two HPV16-E6/E7 transgenic mouse models and from littermate's normal lung. Data analyses were performed using GeneSpring 10 and the functional classification of deregulated genes was performed using Ingenuity Pathway Analysis (Ingenuity® Systems, http://www.ingenuity.com). Results Analysis of deregulated genes induced by the expression of E6/E7 oncoproteins supports the hypothesis of a linkage between HPV infection and SCLC development. As a matter of fact, comparison of deregulated genes in our system and those in human SCLC showed that many of them are located in the Aryl Hydrocarbon Receptor Signal transduction pathway. Conclusions In this study, the global gene expression of transgenic mouse model of SCLC induced by HPV-16 E6/E7 oncoproteins led us to identification of several genes involved in SCLC tumor development. Furthermore, our study reveled that the Aryl Hydrocarbon Receptor Signaling is the primarily affected pathway by the E6/E7 oncoproteins expression and that this pathway is also deregulated in human SCLC. Our results provide the basis for the development of new therapeutic approaches against human SCLC.
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Affiliation(s)
- Tonia Buonomo
- CEINGE Biotecnologie Avanzate, Via Comunale Margherita 482, 80145 Napoli, Italy
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Wiwatanadate P. Lung Cancer Related to Environmental and Occupational Hazards and Epidemiology in Chiang Mai, Thailand. Genes Environ 2011. [DOI: 10.3123/jemsge.33.120] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
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Joh J, Jenson AB, Moore GD, Rezazedeh A, Slone SP, Ghim SJ, Kloecker GH. Human papillomavirus (HPV) and Merkel cell polyomavirus (MCPyV) in non small cell lung cancer. Exp Mol Pathol 2010; 89:222-6. [DOI: 10.1016/j.yexmp.2010.08.001] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2010] [Accepted: 08/02/2010] [Indexed: 10/19/2022]
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Hai-rong J, Peng W, Yong L, Tao N, Xiao-song R, Bao-guo L. Detection of human papilloma virus type 16 E6 mRNA in laryngeal squamous cell carcinoma by in situ hybridization. Chin J Cancer Res 2010. [DOI: 10.1007/s11670-010-0218-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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Ren ZF, Liu WS, Qin HD, Xu YF, Yu DD, Feng QS, Chen LZ, Shu XO, Zeng YX, Jia WH. Effect of family history of cancers and environmental factors on risk of nasopharyngeal carcinoma in Guangdong, China. Cancer Epidemiol 2010; 34:419-24. [DOI: 10.1016/j.canep.2010.04.011] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2010] [Revised: 04/13/2010] [Accepted: 04/14/2010] [Indexed: 12/29/2022]
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