Charged multivesicular body protein 4C (CHMP4C), as a subunit of endosomal sorting complex required for transport-III, is important for the abscission checkpoint in cell division, preventing premature cell division and genetic damage. The present study aimed to assess the role of CHMP4C in cervical cancer and the associated mechanisms. The levels of CHMP4C in normal and cervical cancer tissues were detected by immunohistochemistry. The MTT assay, apoptosis, wound-healing assay, and cell invasion assay were performed. Western blotting was performed to analyze the level of cancer-related proteins following CHMP4C downregulation and the CHMP4C expression following E6 downregulation and miR-543 upregulation. The transfection effectiveness of siRNA, plasmid, and miRNA mimic as well as the expression of miR-543 after silencing E6 were assessed by RT-PCR. The dual-luciferase reporter assay was used to demonstrate a connection site between CHMP4C and miR-543. The results demonstrated that CHMP4C expression in cervical cancer tissues was significantly higher than that in normal tissues. Furthermore, downregulation of CHMP4C expression significantly reduced the proliferation, migration and invasion of cervical cancer cells and significantly increased the rate of apoptosis compared to the si-scramble group. Comparison with the si-scramble group, silencing CHMP4C expression also significantly reduced the expression of Bcl2, Bcl-xL and Survivin, and was associated with a significant increase in Caspase-7 expression. After the knockdown of human papillomavirus (HPV)-encoded E6, in comparison to the si-scramble group, microRNA (miR)-543 expression was significantly elevated and CHMP4C expression significantly decreased. Moreover, a connection site was detected between miR-543 and CHMP4C. These findings indicate that CHMP4C accelerates the tumorigenesis and progression of cervical cancer through the HPV E6/miR-543 axis.

Seborrheic keratosis-like lesion (SKLL) is an extremely rare, morphologically distinct lesion occurring in the cervix and vagina that differs histologically from other squamous intraepithelial lesions in these sites due to its unique morphology, including close resemblance to cutaneous seborrheic keratosis and lack of viral cytopathic effect (koilocytosis). We report a series of 17 cases, describe in detail the morphology and add to the evidence linking SKLL with low-risk human papillomavirus (LRHPV), specifically HPV42, which was detected in 13 cases; in 3 cases, an additional single HPV type (HPV6, 16, 61) was detected. In 2 of the SKLLs, a component of high-grade morphology and block-type p16 immunoreactivity were observed, prompting speculation as to the oncogenic potential of HPV42. Nineteen cases of papillary immature metaplasia, another distinctive LRHPV-associated lesion with some morphologic overlap with SKLL, were HPV42 negative. Independently, HPV42 has recently been implicated as the cause of a rare, aggressive cutaneous tumour, digital papillary adenocarcinoma (DPA), with experimental molecular data supporting the transforming capacity of this virus. These findings, along with the observation that rare anogenital squamous cell carcinomas are associated with HPV42, demonstrate the rare carcinogenic potential of this LRHPV. The association of HPV42 with these 2 unique and distinctive tumours (SKLL and DPA) also illustrates the incompletely understood diversity of HPV genotype-phenotype associations and virus-host interactions and highlights the importance of HPV typing of novel genital and cutaneous tumours.

Sexually transmitted infections (STIs) are an everlasting health issue globally. The military environment is recognised as a high-risk setting. Human papillomavirus (HPV), Chlamydia trachomatis and Neisseria gonorrhoeae are the most frequent STIs worldwide. This prospective cross-sectional pilot study focuses on the prevalence of selected STIs in the female population of the Czech Republic's Armed Forces.

C. trachomatis, N. gonorrhoeae and HPV detection and genotyping were performed between August 2020 and December 2022 in 141 women. Participants were divided into three groups according to their military status-recruits (n=72), active soldiers (n=25) and control civilian group (n=44). Cervical smear tests were performed, and data on STI risk factors were obtained through a questionnaire.

A significant difference in the HPV prevalence between recruits (64.5 %) and both active soldiers (46.4 %) and civilians (47.3 %) was found when adjusted for age (p=0.007 and p=0.01, respectively). Lower age of coitarche (median 16; p=0.005) and smaller agglomeration origin (p=0.013) were reported for military recruits. No difference was proven in other researched risk factors. Associations between HPV detection and the higher number of sexual partners (p=0.013), early coitarche (p=0.016) and single marital status (p=0.002) across the groups were observed. Not a single case of N. gonorrhoeae was detected in any of the 141 participants. The prevalence of C. trachomatis did not differ significantly between the three evaluated groups-recruits, control civilian group, and active soldiers (5.6%, 2.3%, 0%, respectively; p=0.567).

This pilot study showed a significantly higher HPV prevalence in female military recruits compared with both active military and civilian women. Recruits reported earlier coitarche which is a strong STI risk factor. Further study is needed to expand on the findings of this pilot study and generate data to support adjustment of STI preventive measures within the Czech Republic Armed Forces.

Little is known on the vertical transmission of human papillomavirus (HPV) and on the dynamics of HPV among children. Our objective was to determine the risk of HPV recurrence, persistence, and incidence over 2 years of age among children born to HPV-positive mothers.

We conducted the HERITAGE study among pregnant women recruited between 2010 and 2016 in Canada. HPV DNA testing was done on vaginal samples collected during the first and third trimesters of pregnancy, and on conjunctival, oral, pharyngeal, and genital samples collected in children from birth and at every 3-6 months up to 2 years. We estimated the probability of HPV vertical transmission, and of HPV recurrence, persistence, and incidence among children during follow-up. Time to clear HPV among children was estimated using Kaplan-Meier technique.

Among the 422 women with HPV during pregnancy, 390 carried pregnancy to term, and 395 children were born alive including twins/triplets. HPV vertical transmission was estimated at 7.3% (95% confidence interval [CI], 5.0%-10.4%) with a genotype concordance of 85.2%. During the entire follow-up, we observed 91 HPV detections (among 51 children) including 2 recurrent and 1 persistent. Incident genotypes occurred in 26 of the 270 (9.6%) children with valid HPV testing during follow-up. Most HPV infections detected in children cleared with a mean time of 3.9 months (95% CI, 3.6-4.2 months).

HPV vertical transmission and incident HPV occasionally occur during infancy, but the risk of persistence or recurrence is overall very low.

It is crucial to prioritize the detection of precancerous lesions in clinical practice, especially in young women who have not yet made decisions about family planning. Herein, we conducted a retrospective study to track HPV regression among young females who underwent conization in the past five years and identify predictors of persistent HPV infection.

We involved 400 women under the age of 35, who underwent colposcopy-guided biopsy after primary infection with high-risk HPV at the affiliated Hospital of Jiangnan University and were histologically confirmed with LSIL/HSIL between June 2018 and December 2022. Follow-up data was collected at 3 months, 6 months, 12 months and 24 months postoperatively. Clinical characteristics, including age, BMI, marital status, gravidity, contraception method, sexual history, HPV infection duration, HPV vaccination status, preoperative HPV, and cytology status, were analyzed by SPSS 20.0 software.

A total of 400 patients aged 18 to 35 were included, with 354 (88.5%) undergoing cervical biopsy and 92 (23%) undergoing cervical conization. There were no significant differences in age, BMI, marital status, pregnancy history, and HPV vaccination between patients with persistent HPV infection and those with HPV regression after conization. However, the timing of first sexual activity and the use of condom contraception had a statistically significant impact on HPV status.

Duration of sexual life may play a significant role in the development of cervical precancerous, showing a positive correlation. Condoms for contraception can promote HPV regression by creating a physical barrier that blocks the transmission of HPV. Regular follow-up intervals following cervical conization are of greater significance than HPV vaccination.

Sexually transmitted infections (STIs) such as human papillomavirus (HPV), Ureaplasma urealyticum (UU), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and herpes simplex virus type 2 (HSV-2) significantly affect male reproductive health. Coinfections among these pathogens may aggravate disease severity, yet data on their prevalence among male outpatients remain scarce. In this study, we investigated the prevalence of UU, HSV2, NG, CT, and HPV infections and coinfections in the external genitalia of male outpatients in Kunming, Yunnan. HPV genotyping was performed using PCR and Sanger sequencing, while other pathogens were detected using real-time quantitative PCR. Relevant medical records were obtained from the hospital information system. Statistical analyses were conducted to examine associations between coinfections and clinical characteristics. The prevalence rates for UU, HSV-2, NG, CT, and HPV infections in the external genitalia of male outpatients were 33.31 %, 27.04 %, 23.11 %, 11.70 %, and 8.25 %, respectively. The most common coinfection was NG+UU (14.81 %), followed by CT+UU (4.02 %) and CT+NG (1.45 %). Coinfection rates for HSV2 with UU, CT, and NG were 5.35 %, 0.58 %, and 2.03 %, respectively. HPV coinfection rates with UU, CT, NG, and HSV2 were 3.30 %, 0.62 %, 3.57 %, and 0.00 %, respectively. The five most common HPV subtypes were HPV 43, 52, 56, 58, and 33. This study highlights the high prevalence of STIs and coinfections among male outpatients in Kunming, underscoring the urgent need for improved screening and prevention strategies to address these widespread health concerns.

Despite advances in screening and prevention, cervical cancer (CC) remains an unresolved public health issue and poses a significant global challenge, particularly for women in low-income regions. Human papillomavirus (HPV) infection, especially with the high-risk strains, is a primary driver of cervical carcinogenesis. Emerging evidence indicates that integrating HPV testing with existing approaches, such as cervical cytology and visual inspection, offers enhanced sensitivity and specificity in CC screening. HPV infection-associated biomarkers, including HPV E6/E7 oncogenes, p16^INK4a, DNA methylation signatures, and non-coding RNAs, offer valuable insights into disease progression and the development of personalized interventions. Preventive and therapeutic vaccination against HPV, along with tertiary prevention strategies such as the use of antiviral and immune-modulating drugs for HPV-related lesions, show great clinical potential. At the mechanistic level, single-cell RNA sequencing analysis and the development of organoid models for HPV infection provide new cellular and molecular insights into HPV-related CC pathogenesis. This review focuses on the crucial roles of HPV in the prevention, diagnosis, and treatment of CC, with particular emphasis on the latest advancements in screening and disease intervention.

Despite being designated as "noncarcinogenic" human papillomavirus (HPV) types, mono-infection with HPV6 or HPV11 has been found in squamous cell carcinomas (SCCs) at specific sites, including the larynx, penis, anus, and rarely, the lower female genital tract. The association between clinicopathologic features, viral status, and the carcinogenic mechanisms related to these low-risk HPVs remains unclear. The current study characterizes a series of low-risk HPV6 and HPV11-associated SCCs of the uterine cervix (6 cases) and vulva (2 cases). The diagnosis of SCC was made through the identification of stromal invasion in 6 cases. In case 2, the diagnosis of cancer was made after metastases to the sigmoid colon and liver. The patient in case 6 was diagnosed with intramucosal papillary SCC given multiple recurrences. While all tumors displayed a similar verruco-papillary architecture, the cytologic features, and immunostaining patterns suggest 2 groups of lesions: one with high-grade cytology and a high Ki-67 proliferation index (>60% of lesional cells), and the other with low-grade cytology and a low Ki-67 (20% to 30% of lesional cells). The detection of HPV6 in 7 of 8 cases underscores its critical role in carcinogenesis at these anatomic sites. Case 8 represented the only patient who was infected with HPV11 and who had a well-controlled human immunodeficiency virus infection. Correlating with viral status, all cases, except case 7, demonstrated a negative or focal p16 staining pattern. In case 7, despite a block pattern of p16 staining often seen in predicting high-risk HPV, we employed several methods to confirm HPV6 as the sole HPV infection. Although this descriptive study does not establish an etiological mechanism for how HPV6/11 leads to malignant transformation, our results exclude the possibility of viral integration through a quantitative polymerase chain reaction-based analysis of the E2/E6 ratio. Our study highlights and expands upon the clinicopathologic features of a distinct group of low-risk HPV6/11-associated SCCs in the cervix and vulva. Although rare, recognizing this group of lesions is important for pathologists and oncologists, as it provides a basis for guiding appropriate prevention strategies and treatment modalities based on the viral type.

Reproductive cancers, such as ovarian, cervical, and endometrial carcinomas, have a poor prognosis in metastatic stages. Researchers are continuously seeking improved and safer methods to target cancer-related oncoproteins, addressing the limitations of current treatments, including their limited effectiveness, drug resistance, and off-target effects. Recent advancements in understanding the molecular mechanisms involved in the progress of reproductive cancers have provided valuable insights into potential targeted therapies. By engaging with oncoproteins and co-chaperones, heat-shock protein 90 (HSP90) regulates signaling networks and fixes protein folding errors in cancer cells. The potential of HSP90 inhibition as cancer-targeted treatments is underscored by the continuous discovery and testing of novel HSP90-targeted molecules for their antitumor properties in preclinical and clinical settings. Therefore, this study aims to shed light on the mechanism and recent research breakthroughs of HSP90, as well as provide an in-depth review of their therapeutic potential in reproductive cancers.

Objectives were to determine the prevalence/incidence of HPV-related dysplasia and clearance/acquisition rates of high-risk HPV (HR-HPV) genotypes in genital mucosa of women with HIV (WWHIV) and oropharyngeal and anal mucosa of people with HIV (PWH) and to evaluate factors related to HR-HPV infection in oropharyngeal mucosa at 12-months.

Prospective, longitudinal study with 12-month follow-up, enrolled PWH between December 2022 and April 2023. At baseline and 12 months, HIV-related clinical and analytical variables were recorded, oropharyngeal mucosa exudates were taken for PCR studies for human papilloma virus (HPV) and other sexually transmitted infections, whereas anal and female genital samples were self-sampled for HPV detection and genotyping by PCR and thin-layer cytology.

Two hundred and seventy-six PWH with mean age of 45.3 years, 79% men, 24.3% with history of AIDS, 100% under antiretroviral therapy (ART), and 30.1% with completed HPV vaccination. HPV infection prevalence in oropharyngeal mucosa was 11.6% at baseline, most frequently by genotype 16 (2.2%), without dysplasia. No oropharyngeal dysplasia was observed at 12 months, and HR-HPV clearance and acquisition rates were 5.5 and 4.4%, respectively. Incidence of anal high grade squamous intraepithelial lesion (HSIL) was 1811.6 cases × 100 000 people-year, and HR-HPV clearance and acquisition rates were 16.2 and 25.6%, respectively. Incidence of CIN2/CIN3 or cervical cancer was zero, and HR-HPV clearance and acquisition rates were 11.3 and 7.5%. HIV-RNA viral load less than 50 copies/ml protected against HPV infection in oropharyngeal mucosa [97.2 vs. 87%, hazard ratio 0.044; 95% confidence interval (95% CI 0.042 - 0.956)].

Among PWH, HSIL incidence and HR-HPV acquisition rate are higher in anal versus oropharyngeal and genital mucosae. Nondetectability protects against oropharyngeal HPV infection.

Human papillomavirus (HPV) is a widespread and diverse group of viruses that are responsible for various clinical conditions, including cervical cancer, one of the most common cancers among women worldwide. In Africa, the prevalence and distribution of HPV genotypes vary significantly across different regions. In this study, we analyzed the genetic diversity, geographical distribution, and evolutionary dynamics of HPV genotypes across various African countries to provide insights into the prevalence and transmission patterns of HPV. A total of 9203 genome sequences of HPV isolates from cervical samples from 21 African countries were obtained from the GenBank database. Of these, 184 were identified as unique sequences and were used for further analysis. Phylogenetic analysis demonstrated that the African HPV sequences share genetic ancestry with European sequences, whereas American isolates are less closely related. Migration analysis revealed a significant asymmetry in HPV flow, with migration rates from Africa to Europe consistently exceeding those in the opposite direction, suggesting that Africa is a major source of HPV genetic variants entering Europe. This interconnectedness underscores the intricate interplay of historical, regional, and cultural determinants that have collectively contributed to shaping the genomic landscape of African strains. The geographically variable HPV genotypes 35, 31, 16, 18, 58, 45, 7, and 66 are the most common in Africa. Algeria, Morocco, Rwanda, and Guinea have diverse genotypes, and the rates of infection are highest in the Republic of Congo and Chad.

This study aimed to evaluate the potential of real-time optoelectronic device (TruScreen™; TS; TruScreen Group Limited, New Zealand) as an alternative or adjunct to Pap Smear (Liquid Based Cytology (LBC)) for cervical cancer screening.

We conducted a prospective observational pilot study involving 507 women who were routinely followed at gynecology clinics. All participants underwent TS and LBC examinations after study enrolment. Those with abnormal findings were referred for colposcopy and cervical biopsy within one month.

Overall, 507 women fulfilled the eligibility criteria and were included in this study, of which 30 women (5.9%) had abnormal TS findings and underwent colposcopy. Thirteen women (43.3%) had low-grade lesions, and only one (3.3%) had a high-grade lesion. Regarding biopsy findings, three women had cervical intraepithelial neoplasia (CIN) 1, two women had 'CIN2 + , and one had glandular hyperplasia. The TS yielded a sensitivity of 83.3% (95% CI: 35.9-99.6%) and a specificity of 95% (95% CI: 92.7- 96.8%) for the detection of cervical abnormality, compared to 66.7% (95% CI: 22.3-95.7%) and 98.2% (95%: CI 96.6%-99.2%) of the Pap smear, respectively. The difference between both screening tools was not statistically significant (p = 0.91). The sensitivity (100%, 95% CI 15.6-100%) and specificity (95.6%, 95% CI 93.4-97.2%) of TS and Pap smear for 'CIN2 + lesions were notably high.

TS demonstrated potential as a screening tool for cervical neoplasms in this preliminary study. The tool did not require cervical samples, laboratory equipment, or highly trained personnel. While our findings suggest the potential for real-time and accurate screening, further research with a larger sample size is necessary to confirm its reliability and practicality.

Knowing the geographical distribution of lineages and sublineages of each HPV type is beneficial for the epidemiological and evolutionary studies of this virus. However, no studies have analyzed the variants of HPV 33 and 35 in Iranian women. To investigate the sequence variation of HPV 33 and 35 E6 gene, 42 and 92 samples were analyzed using nested PCR and sequencing, respectively. Sublineage analysis of HPV 33 showed that most of the samples belonged to the A2 sublineage (85.8%) and the remaining were classified to the A1 sublineage. Four mutations at positions A132C, A213C, A364C, and A480T were detected, among which two mutations A213C and A364C led to amino acid changes corresponding to positions K35N and N86H of amino acid, respectively, in 85.8% of samples. For HPV 35, two sublineages A1 and A2 were found in studied samples with a prevalence of 84.8 and 15.2%, respectively. Seven nucleotide changes were observed at positions of C127G/T, A130C, A131C, C136T, G249T, A326G, and C341T. Three of these mutations including A130C, G249T, and C341T resulted in amino acid changes at positions of E7D, C47F, and R78W in 4.4%, 3.3%, and 9.8% of samples, respectively. Concerning HPV 33 or 35 distinct lineages by histology/cytology status, no statistically significant differences were observed. Our results indicated that sublineages A2 of HPV 33 and A1 of HPV 35 were dominant in Tehran, Iran. However, more studies with larger sample sizes from different histopathological stages of cervix in various geographical regions of Iran are necessary to evaluate the pathogenicity risk of HPV 33 and 35 (sub)lineages in Iranian women with cervical cancer in the future.

Cervical cancer (CC), the fourth most common cancer in women, is caused predominantly by human papillomavirus (HPV). Although measuring serum squamous cell carcinoma antigen (SCC Ag) can be useful for detecting recurrence of SCC, a major type of CC, its prognostic value remains unclear. This study focuses on the utility of circulating cell-free HPV (ccfHPV) DNA in plasma as a biomarker, with particular emphasis on its relevance to high-risk HPV subtypes prevalent in Japan.

A prospective study of 26 CC patients and 23 females diagnosed with pre-cancerous lesions was conducted. Patients were selected carefully to include only those with single high-risk HPV subtypes (i.e., HPV16, 18, 52, or 58), reflecting regional HPV epidemiology. ccfHPV DNA was isolated from plasma and analyzed by droplet digital PCR targeting the HPV E7 genes.

The detection rate of ccfHPV DNA in CC patients before clinical treatment was 57.7%. The detection rate correlated significantly with tumor size (r = 0.624, P < 0.01) and clinical stage (r = 0.844, P < 0.01). No ccfHPV DNA was detected in the females with pre-cancerous lesions. By contrast, of the 13 concurrent chemoradiotherapy cases, two relapsed within 6 months post-treatment. In those cases, ccfHPV DNA levels rose earlier than SCC Ag levels. The 11 CC cases in which no ccfHPV DNA was detected within 1 month post-treatment did not relapse.

ccfHPV DNA is a useful biomarker for advanced-stage CC and for predicting prognosis, particularly in the Japanese clinical setting.

Limited data are available about the distribution of human papillomavirus (HPV) among women undergoing cervical cancer screening in Mozambique. We describe the prevalence of high-risk HPV risk groups detected in women who participated in the MULHER Study, a prospective trial of Mozambican women undergoing cervical cancer screening with HPV testing.

From January 2020 to January 2023, 9,014 women aged 30-49 years in Maputo City and Gaza Province, Mozambique underwent cervical cancer screening. Cervicovaginal samples were self-collected (97.5%) or provider-collected (2.5%) and primary HPV testing was performed using the GeneXpert HPV testing platform (Cepheid Inc, USA) which provided data on HR-HPV risk groups: HPV16, HPV18/45 and 11 other HR-HPV types in aggregate. Women with a positive HR-HPV test underwent visual assessment using dilute acetic acid applied to the cervix for treatment decisions.

Of the 9,014 women enrolled in the MULHER Study, 8,954 (99.3%) had a valid HPV test result. Of those, 2,805 (31.3%) tested positive for at least one HR-HPV group: HPV16 (n = 475, 16.9%), HPV18/45 (n = 686, 24.6%) and other HR-HPV (n = 2,150, 77.1%). A total of 17.8% were positive for multiple HPV HR groups. HR-HPV infection prevalence was higher among women living with HIV (WLWH) than HIV-negative women (39.7% vs. 24.3% respectively; p < 0.001). WLWH were more likely to test positive for HPV18/45 (p = 0.03) and for two or more HR-HPV risk groups (P < 0.0001) compared with HIV-negative women. HPV16 was the most frequently detected HR-HPV group (56.7%) among women diagnosed with invasive cervical cancer.

HR-HPV prevalence was high among Mozambican women aged 30-49 years, especially among WLWH, consistent with the high burden of cervical cancer in this population. HPV16 was the most common HR-HPV group among women with cervical cancer. Further study is needed to determine the role of HR-HPV genotyping in follow-up and treatment in Mozambique.

Human papillomavirus (HPV) is a major cause of cancers and benign lesions. High-risk (HR) types, including HPV16 and HPV18, are strongly implicated in cervical and other malignancies, while low-risk (LR) types, such as HPV11, are predominantly associated with benign conditions. Although the immune evasion of HPV oncoproteins E6 and E7 are extensively studied, the immunomodulatory functions of the E2 protein remain poorly underexplored. This study elucidates the role of HPV11 and HPV16 E2 proteins in modulating innate immune responses, focusing on their interaction with key innate antiviral signaling pathways. We demonstrate that HPV11 and HPV16 E2 proteins effectively suppress the activation of pivotal antiviral signaling pathways, including RIG-I/MDA5-MAVS, TLR3-TRIF, cGAS-STING, and JAK-STAT. Mechanistic analyses reveal that E2 proteins interact with the core components of type I interferon (IFN)-inducing pathways, inhibiting IRF3 phosphorylation and nuclear translocation, thereby attenuating IFN expression. Additionally, E2 disrupts the JAK-STAT signaling cascade by preventing the assembly of the ISGF3 complex, comprising STAT1, STAT2, and IRF9, ultimately inhibiting the transcription of interferon-stimulated genes (ISGs). These findings underscore the broader immunosuppressive role of HPV E2 proteins, complementing the well-established immune evasion mechanisms mediated by E6 and E7. This work advances our understanding of HPV-mediated immune evasion and positions the E2 protein as a promising target for therapeutic strategies aimed at augmenting antiviral immunity in HPV-associated diseases.

Cervical cancer is primarily attributed to high-risk human papillomavirus (HPV), specifically genotypes 16 and 18. The introduction of HPV vaccines aimed to reduce the incidence of cervical cancer.

This study reviewed cases of High-Grade Squamous Intraepithelial Lesion (HSIL) and Atypical Squamous Cells Cannot Exclude HSIL (ASC-H) with positive high-risk HPV and HPV genotyping data. The prevalence of HPV genotypes 16/18 and non-16/18 was compared in cases with high-grade intraepithelial neoplasia (IN2+), across different ethnicities and with HPV vaccination status.

A total of 274 patients (94 HSIL and 180 ASC-H) were evaluated. HPV non-16/18 was significantly more prevalent in ASC-H (68%) than in HSIL patients (50%); (P = 0.003). HPV non-16/18 was more common in cases without -IN2+ (69%), but a significant proportion of IN2+ cases were also positive for non-16/18 HPV genotypes (56%); (P = 0.04). Overall, HPV non-16/18 was more prevalent in all ethnic groups. There was a trend to a higher prevalence in non-white and vaccinated compared with white and nonvaccinated women respectively, but the difference was not significant.

HPV non-16/18 genotypes are more prevalent than HPV 16/18, even in women with high-grade lesions with a greater shift towards non-16/18 genotypes in non-white and in vaccinated women. The study suggests the need for extended HPV genotyping and vaccines targeting a broader range of HPV types to include HPV non-16/18 to improve prevention, particularly in certain ethnic groups.

Head and neck region squamous cell carcinoma (HNSCC) is a heterogeneous disease that can be categorized into human papillomavirus (HPV)-positive (20 %) and HPV-negative (80 %) subtypes. However, the prevalence of HPV genotypes is not clear in Pakistan. This study investigated how common the HPV-16 genotype is in patients with HNSCC in the Southern Punjab region of Pakistan, and the specific molecular features of this genotype.

For this cross-sectional study, 85 tissue samples were collected from diagnosed cases of HNSCC. Formalin-fixed paraffin-embedded tissue sections were used for genomic DNA extraction. The L1 region was amplified using GP5+ and GP6+ primers to detect HPV DNA. Real-time PCR was conducted to genotype high-risk HPV (HR-HPV). Whole genome sequencing was used for phylogenetic analysis of HPV-16 and to detect mutations/single nucleotide polymorphisms (SNPs).

Among the 85 samples, 7.1 % were positive for HPV, where 4.7 % were positive for HPV-16 and 2.4 % were positive for HPV-18. A significant association was found between HR-HPV positivity and histological grade (p < 0.05). The HPV-16 genome sequence obtained in this study was closely related to those from Thailand, the United States, India, China, and Europe, and 11 mutations/SNPs were detected in the sequenced genome, where four were novel.

The findings obtained in the present study demonstrate the low prevalence of HR-HPV associated HNSCC in Pakistan. Phylogenetic analysis showed that HPV-16 genome isolated and sequenced in this study had a distinct genetic structure and it also shared similarities with genomes reported from Thailand, the United States, India, China, and Europe.

To determine whether intrauterine device (IUD) use is associated with a significantly increased risk of abnormal cervical cytology.

A retrospective cohort study was carried out at the University of Campinas, Campinas, SP, Brazil. Data came from medical records of 2,963 women from a family planning clinic who had undergone at least one cervical cytology for screening between 1990 and 2017. Women were split into three groups: users of either copper (Cu)- or the levonorgestrel 52 mg-IUD (2,305) and users of other contraceptive methods (658). The dependent variable was the cytological results as normal and abnormal, based on the Bethesda System. The most severe cytological result of each participant was considered and when all her results were normal, the last one was considered.

IUD use was associated with a lower risk of abnormal cervical cytology after adjusting for the number of cytology assessments per participant (RR 0.74; 95% CI 0.55;0.99; p = 0.049). Abnormal cervical cytology was more common in women with multiple cytology assessments and a longer duration since sexual debut. For each additional cytology test, the risk increased by 33.8% (p < 0.001), and for every additional year since sexual debut, the risk increased by 6.2% (p < 0.001). A lower incidence of abnormal cervical cytology was observed among women with a history of caesarean delivery, with a 24.9% reduction in risk per additional caesarean (p < 0.001). IUD users underwent more cervical cytology assessments than non-IUD users.

We identified low risk of abnormal cervical cytology among IUD users.

Observational and experimental studies have provided substantial evidence supporting a link between cervical cancer and human papillomavirus (HPV) infection. Nevertheless, there is uncertainty regarding the association of benign and malignant cancers with HPV infection.

The study was divided into two approaches, Mendelian randomization (MR) and multivariate Mendelian randomization (MVMR), to investigate the link between HPV and both benign and malignant cancers. This study employed genetic variants as instrumental variables to mitigate potential biases arising from confounding factors and reverse causality. In 338 cases and 1000 controls in the European ancestry of Germany, independent genetic variations were identified as having a substantial correlation (p < 5 × 10-5) with exposure and HPV infection. The outcome variables data of various carcinomas were acquired from the Genome-wide association summary data. Meanwhile, benign tumors from the FinnGen and UK Biobank (UKB) consortium were acquired as well.

Following correction for multiple testing, the MVMR method was employed and the causal association was investigated between genetic liability to HPV infection and various malignancies, including bone and articular cartilage, bladder cancer, secondary malignant neoplasm of the liver, prostate cancer, as well as benign tumors including melanocytic naevi of the lip, brain, bronchus and lung, lip, mouth and pharynx, pancreas, and haemangioma and lymphangioma, and female genitalia.

From a genetic standpoint, HPV may contributes to the formation of benign and malignant tumors in female genital cancer as well as malignancies in other regions of the body, which should inform public health policy.

Human papillomavirus (HPV) genotyping is essential for cervical cancer screening and prevention. The AllplexTM HPV28 real-time PCR kit, using different chemistry and results analysis compared with its predecessor, the AnyplexTM II HPV28 kit, has recently been launched. This study aims to compare the AllplexTM HPV28 and AnyplexTM II HPV28 assays in detecting and genotyping the 13 high-risk (HR)-HPV types.

Between 2022 and 2023, 459 cervical samples from women undergoing cervical cancer screening were selected. These samples were analysed by liquid-based cytology and tested by both kits concurrently.

AllplexTM HPV28 Ct values correlated well with AnyplexTM II HPV28 signal intensity scores. No significant differences between assays were observed in overall and genotype-specific HR-HPV prevalence determined in all samples and according to cytological results. In addition, no significant differences were identified between assays in the detection of single and multiple HR-HPV infections. Most of the discordant results corresponded to samples showing weak HR-HPV signals and multiple HR-HPV types.

Our results demonstrate that the AllplexTM HPV28 kit can be used for HPV genotyping, with results overall similar to those obtained with the AnyplexTM II HPV28 kit and the addition of Ct values for patient follow-up. The clinical implications of the potentially reduced sensitivity of the AllplexTM HPV28 kit in detecting HPV31 (p =  0.07) and HPV39 (p =  0.08) warrant further investigation in subsequent studies.

HPV infection has been associated with squamous cell carcinoma of the head and neck, genital tract and anal canal. HPV has two oncogenic genes, including E6 and E7, which are responsible for carcinogenesis. Ki67 and p16 have been used as biomarkers of HPV genome integration in the host cell.

To analyse the prognostic role of HPV status and p16/Ki67 expression in malignant lesions of the anal canal.

A retrospective study conducted from 2013 to 2016, including 40 biopsies.

Histologic classification of the samples was: 9 samples of invasive carcinoma (ASCC); 9 of anal intraepithelial neoplasia (AIN) II/III; 8 condylomas; 14 non-tumoral lesions. For HPV detection we used nested-real time PCR for E6/E7. The determination of p16INK4a and Ki67 was carried out by immunohistochemistry. Additionally, demographic information was analysed. Among the 9 ASCC cases, 8 were p16-Ki67 positive and high-risk HPV positive. Of the 9 AIN II/III cases, 8 (88.8%) were HR-HPV and p16-Ki67 positive; all cancer cases were HPV-16. Out of the 8 condyloma cases, 2 (25%) were HR/LR HPV, 5 (62.5%) were LR-HPV, and 100% p16/Ki67 negative. Of the 14 non-tumoral lesions, all biomarkers tested negative.

High- and low-risk HPV genotyping helps predict the prognosis of anal canal lesions. High-risk HPV infection and p16 overexpression are associated with malignant tumoral lesions.

SUMMARYHuman papillomaviruses (HPVs) are small DNA viruses that are responsible for significant disease burdens worldwide, including cancers of the cervix, anogenital tract, and oropharynx. HPVs infect stratified epithelia at a variety of body locations and link their productive life cycles to the differentiation of the host cell. These viruses have evolved sophisticated mechanisms to exploit cellular pathways, such as DNA damage repair (DDR), to regulate their life cycles. HPVs activate key DDR pathways such as ATM, ATR, and FA, which are critical for maintaining genomic integrity but are often dysregulated in cancers. Importantly, these DDR pathways are essential for HPV replication in undifferentiated cells and amplification upon differentiation. The ability to modulate these DDR pathways not only enables HPV persistence but also contributes to cellular transformation. In this review, we discuss the recent advances in understanding the mechanisms by which HPV manipulates the host DDR pathways and how these depend upon enhanced topoisomerase activity and R-loop formation. Furthermore, the strategies to manipulate DDR pathways utilized by high-risk HPVs are compared with those used by other DNA viruses that exhibit similarities and distinct differences.

This study aimed to verify the relation between gastrin-releasing peptide receptor (GRPR), oncogenic Human Papillomavirus (HPV) and cervical lesions severity.

GRPR mRNA levels were evaluated in cervical cancer-derived cell lines and in primary keratinocytes expressing HPV16 oncogenes by RT-PCR. GRPR protein expression was assessed by immunohistochemistry in organotypic cell cultures derived from keratinocytes transduced with HPV16 oncogenes and in 208 cervical samples, including 59 non-neoplastic tissue, 28 cervical intraepithelial neoplasia grade 3 (CIN3), 44 squamous cell carcinomas (SCC) and 77 adenocarcinomas (ADC). Generic primers (GP5+/GP6+) were used to identify HPV infection in tissue samples. Experiments involving cell lines were analyzed through non-parametric tests (Kruskal Wallis), and Fisher's Exact Test for human tissues samples. All statistical tests were considered significant at p <0.05. Immunohistochemical evaluation was conducted independently and blindly by two observers (AD- LO). Any discordant findings were resolved through discussion to reach a consensus score.

GRPR mRNA levels were not increased in cells expressing HPV16 or HPV18 oncogenes. However, at the protein level, GRPR was upregulated in organotypic cell cultures containing HPV oncogenes. Besides, it was identified an association between GRPR expression and cervical lesion severity (p < 0.0001). The detection rate of high-risk HPV DNA was directly correlated with cervical disease. Nonetheless, HPV infection was not directly associated with GRPR in cervical samples.

GRPR expression is highly predictive of cervical lesion severity, irrespective of HPV infection and might contribute to improving patient's therapeutic management as well as being used a marker of disease progression.

To systematically evaluate the association between a history of Condyloma acuminatum, human papillomavirus (HPV) infection in prostate tissue, and prostate cancer in Mexican men, as well as to assess the prevalence of high- and low-risk HPV genotypes in prostate tissue.

A systematic review and meta-analysis were conducted on studies that investigated the presence of HPV in prostate tissue or a history of condyloma and their association with prostate cancer. Data were extracted from PubMed and Web of Science, and the Newcastle-Ottawa Scale was used to assess study quality. Pooled odds ratios (OR) and the prevalence of HPV genotypes were calculated using a random effects model.

Eight case-control studies were included, comprising 1,059 cases and 1,768 controls. A significant association was found between the presence of HPV in prostate tumour tissue and prostate cancer (OR 2.34, 95% CI 1.52-3.60). Meanwhile, a borderline statistically significant relationship was observed between a history of Condyloma acuminatum and prostate cancer (2.26, 95% CI 1.00-5.11). The prevalence of high-risk HPV was 77% (95% CI 69-84%), while the prevalence of low-risk HPV was 23% (95% CI 16-31%). No significant publication bias or heterogeneity was detected.

The presence of HPV in prostate tissue is significantly associated with increased odds of prostate cancer in Mexican men. These findings suggest that HPV may play a role in the development of prostate cancer and underscore the importance of further investigation into HPV screening and vaccination as potential preventive measures.

Background and Objectives: Interest in defining the characteristics of the cervicovaginal microbiota (CVM) in invasive cervical cancer (ICC) is growing, particularly concerning Lactobacillus species, as evidence suggests that these may differ in affected women and potentially interact with Human Papillomavirus (HPV) infection. Understanding these features could have important implications for disease management. Thus, this study aims to systematically review the main characteristics of available literature exploring the relationship between CVM diversity, Lactobacillus profiles, and HPV in ICC; Methods: A comprehensive bibliographic search was conducted across databases, including Medline, Embase, Scopus, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov, in accordance with the to the PRISMA guidelines. The review included studies that met the following inclusion criteria: studies comparing CVM in women with ICC to controls, focusing on Community State Types (CSTs), Lactobacillus profiles, and microbial diversity. Exclusion criteria included commentaries, letters, reviews, and studies without control groups. Variables were analyzed using the Kruskal-Wallis and Fisher's exact tests, with statistical significance level set at 0.05. Data analysis was conducted and reviewed in a blinded manner. Results: A total of 28 studies published between 2015 and 2024 met the inclusion criteria. A total of 2082 patients were included, with 323 (41.9%) of the 770 cases testing positive for HPV and 327 (24.9%) of the 1312 controls testing positive for HPV. A total of 18 studies specifically examined HPV genotypes. Cervical swabs were employed in 19 out of 28 studies (67.9%), while vaginal swabs were used in 17 studies (60.7%). Additionally, two studies included samples collected via cervical biopsy (7.1%), four studies utilized cervicovaginal lavage (14.3%), and one study used a cervical brush for sample collection (3.6%). Regarding microbiota profiling, 26 studies (92.9%) employed 16S rRNA analysis, while one study (3.6%) utilized whole-genome sequencing (WGS), and another (3.6%) used 16s rDNA. A total of 10 studies (35.7%) examined the distribution of CSTs. Five studies (17.9%) reported on Lactobacillus profiles. Different levels of Lactobacillus crispatus and Lactobacillus iners were observed, along with variations between Lactobacillus-dominant and Lactobacillus-depleted communities. A total of 22 studies (78.6%) assessed α-diversity, and 17 studies (60.7%) examined β-diversity; Conclusions: This study emphasizes the heterogeneous features of the studies exploring the association between alterations in the CVM, HPV, and the development of ICC, suggesting the need for further research to better understand this relationship. These findings could inform new strategies for prevention and treatment.

High-risk human papillomavirus E6 oncoprotein is a model system for the recognition and degradation of cellular p53 tumor suppressor protein. There remains a gap in the understanding of the ubiquitin transfer reaction, including placement of the E6AP catalytic HECT domain of the ligase concerning the p53 substrate and how E6 itself is protected from ubiquitination. We determined the cryoelectron microscopy (cryo-EM) structure of the E6AP/E6/p53 complex, related the structure to in vivo modeling of the tri-molecular complex, and identified structural interactions associated with activation of the ubiquitin ligase function. The structure reveals that the N-terminal ordered domain (NOD) in E6AP has a terminal alpha helix that mediates the interaction of the NOD with the HECT domain of E6AP and protects the HPV-E6 protein from ubiquitination. In addition, this NOD helix is required for E6AP ligase function by contributing to the affinity of the E6-E6AP association, modulating E6 substrate recognition, while displacing UbcH7.

One of the most significant breakthroughs in cancer research has been the identification of persistent infection with certain human papillomaviruses (HPV) genotypes as the cause of cervical cancer. Since then, a range of diagnostic and therapeutic methods has been developed based on this discovery. This article aims to describe the latest updates in the biology, prevention, and treatment of HPV-related cervical cancer. The current state of knowledge regarding vaccinations, diagnostic tests, and cervical cancer therapies is presented. The latest WHO guidelines on vaccinations are presented, as well as announcements of upcoming changes. The final part of the article summarizes promising new diagnostic and treatment methods, as well as perspectives and the latest research findings on self-administered diagnostic tests, the use of therapeutic vaccines, and circulating cell-free DNA in diagnosis. Despite the significant progress made in recent years, the strategy based on vaccination and testing remains the cornerstone in the fight against HPV-related cervical cancer.

The role of transforming growth factor-beta (TGF-β) is dual, such that, it inhibits tumor development in initial stage and promotes metastasis in later stage. The present study is aimed to analyse the relevance of different types of TGF-β and their receptors on the overall survival (OS) and TGF-β driven gene expression in individuals with cervical cancer (CC) using ONCODB and GEPIA databases. The in-silico gene expression analysis showed, TGF-β1 and TGFβR2 are upregulated in cells infected with human papilloma virus (HPV)16, whereas, TGF-β2, TGFβR1 and TGFβR3 expression were downregulated. In HPV 18 infected cells, TGF-β1, TGF-β2 and TGFβR1 were downregulated, meanwhile, TGF-β3, TGFβR2 and TGFβR3 were upregulated. OS analysis of CC patients with different TGF-β expression revealed that, TGF-β1, TGF-β2, TGF-β3 and TGFβR2 were associated with reduced survival rate. Further, we identified four microRNAs (miRNAs) (hsa-miR-21-5p, hsa-miR-29b-3p, hsa-miR-101-3p and hsa-miR-130a-3p) interacted favorably with TGF-β in HPV 16 and 18 positive samples using MIENTURNET. This present review further emphasizes that, targeting TGF-β could be a novel and futuristic approach for CC management and therapeutics.

An increasing number of studies indicate that the gut, cervical, and vaginal microbiota may play crucial roles in the development of cervical cancer (CC). However, the interactions between the microbiota and the host are yet unknown. To address this gap, a systematic review and meta-analysis were conducted to assess the microbiota alterations in a variety of body locations, including the gut and genital tract.

Electronic searches of PubMed, Embase, Web of Science, and the Cochrane Library were conducted to retrieve eligible papers published from January 1, 2014, to January 1, 2024 (PROSPERO: CRD42024554433). This study was restricted to English-language studies reporting on alpha diversity, beta diversity, and relative abundance, as well as on patients with CC whose microbiota had been analyzed via next-generation sequencing technologies. To assess the risk of bias (RoB), we utilized the Newcastle‒Ottawa Quality Assessment Scale (NOS) and the ROBINS-I tool. For the meta-analysis, we employed Review Manager 5.4.

Thirty-six eligible studies were included in this review. The Chao1 index (SMD = 0.96, [95% CI: 0.71, 1.21], I2 = 0%) and the Shannon index (SMD = 1.02, [95% CI: 0.53, 1.50], I2 = 85%) values from vaginal samples were significantly greater in patients than in the controls. In the cervical samples, the Shannon index value (SMD = 1.29, [95% CI: 0.61, 1.97], I2 = 93%) significantly increased, whereas the Chao1 index value did not significantly differ (SMD = 0.50, [95% CI: -0.46, 1.46], I2 = 89%). The Shannon index value (SMD = 0.25, [95% CI: -0.22, 0.72], I2 = 38%) did not significantly differ across the gut samples. The majority of studies (19/25) indicated that the patients and noncancer controls differed significantly in terms of beta diversity. Cancer-associated changes were observed, with a dramatic decrease in the Lactobacillus genus and significant increases in pathogenic bacteria, including the Anaerococcus, Peptostreptococcus, Porphyromonas, Prevotella, and Sneathia genera. Additionally, the impact of antineoplastic therapies on microbial diversity was inconsistently reported across several studies.

This systematic review elucidates the microbiota alterations associated with the prevalence of CC and its response to anti-tumor therapies, aiming to provide insights for future research directions and precision medicine strategies to enhance women's quality of life.

CRD42024554433.

Cervical cancer and its precursors (cervical intraepithelial neoplasia (CIN)) represent a current major public health concern. Currently, the treatment of choice for patients with HSILs (high-grade intraepithelial lesions) is surgical treatment-LEEP or cold-knife conization-except for in pregnant women, where it may have significant future consequences. In this paper, we aim to review the current evidence regarding the efficacy of non-surgical approaches for CINs. Therefore, we searched Google Scholar and PubMed for papers on CIN treatments; 91 studies published in English were included in the analysis. The results of the reviewed studies were variable depending on the agent and methodology used. Overall, the remission rates of CIN II ranged from 43 to 93%. However, for some agents, the results were contradictory. Once topical agents have been proven to be effective, they could be used as an alternative to surgical methods in treating HPV-associated CIN, with fewer adverse effects. The use of local agents could allow for more personalized treatments for patients with CINs. Future directions were also sought.

O3-O2 therapy is an alternative medical treatment that introduces a mixture of O3-O2 into the body for therapeutic purposes. The objective of this study is to evaluate its margins of applicability in the eradication of HPV infection from the lower gynecological tract by means of vaginal insufflation.

An in-depth review of the international literature on this topic is carried out; in addition, O3-O2 therapy is compared with other treatments currently available in terms of its advantages, disadvantages, and exploited technologies.

The possible benefits and limitations of O3-O2 vaginal insufflation are explained in detail; overall, it appears to be an interesting tool as part of complex management to prevent HPV-related cancers of the lower gynecological tract in infected patients.

The rationale and guidelines of this innovative procedure have been successfully illustrated, providing the technical specifications for further developments.

Anal high-risk human papillomavirus (HRHPV) testing-based anal cancer screening gay and bisexual men (GBM) is associated with high sensitivity, but low specificity. We report the potential role of triage use of anal cytology with HRHPV testing in detecting 12-month persistent anal high-grade squamous epithelial lesions (HSIL) in a cohort of GBM in Sydney, Australia. Participants were GBM from the Study of the Prevention of Anal Cancer (SPANC) who underwent annual anal HPV testing, cytology, and high-resolution anoscopy (HRA)-guided histology. The sensitivity and specificity of five screening algorithms based on HRHPV test results with triage use of anal cytology (atypical squamous cells of undetermined significance (ASCUS) and atypical squamous cells, cannot exclude HSIL (ASC-H) used as referral thresholds) were compared to these of HRHPV testing and anal cytology alone. A total of 475 men who had valid HRHPV, cytological, and histological results at both baseline and first annual follow-up visits were included, median age 49 years (inter-quartile range: 43-56) and 173 (36.4%) GBM with human immunodeficiency virus. Of all triage algorithms assessed, two had comparable sensitivity with HRHPV testing alone in detecting persistent anal HSIL, but ~20% higher specificity and 20% lower HRA referral rates. These two algorithms involved the immediate referral of those with HPV16 and for those with non-16 HRHPV either immediate or delayed (for 12 months) referral, depending on cytology result at baseline. Triage use of anal cytology in GBM testing positive for anal HRHPV increases specificity and reduces referral rates while maintaining high sensitivity in detection of HSIL.

Background The adolescent human papillomavirus (HPV) vaccination rate is relatively high in developed countries and it is not widespread in Turkiye. This paper explores what factors influence the decision on the acceptance of the HPV vaccine by adolescents. Methods Data from 206 adolescents was gathered via a survey completed after consent from the parents and themselves between May 2022 and September 2022. The survey content was based on the Carolina HPV Immunization Attitudes and Beliefs Scale (CHIAS), each question being based on a 5-point Likert scale, together with additional questions to discover demographic factors. The participants were also questioned about their level of knowledge of HPV and its source. At the end of the questionnaire, once the adolescents were briefed on HPV vaccination by a doctor, questions about immunization against HPV were again redirected. Results The age of 206 participants was between 12 and 26 years old, and it was found that the knowledge level about the HPV vaccine increases as the age gets older. The adolescents believe that HPV protects more from cervical cancer than genital warts. 8.7% (n=18) of adolescents thought that the HPV vaccine could have long-term adverse effects. 33.5% (n=69) of them stated that their families could not afford the vaccine. After they were given more knowledge, it was found that they were more willing to have HPV immunization. Conclusions It is important to realize that teenagers' opinions can shift significantly, particularly in the context of informed decision-making and the provision of government financial assistance to parents. The comprehension of teenagers' perspectives and the extent of their knowledge regarding HPV is of paramount importance, given the likelihood of it being influenced by their own acceptance of the vaccine.

High-risk human papillomaviruses are well-established drivers of several cancer types including cervical, head and neck, penile as well as anal cancers. While the E6 and E7 viral oncoproteins have proven to be critical for malignant transformation, evidence is also beginning to emerge suggesting that both host pathways and additional viral genes may also be pivotal for malignant transformation. Here, we focus on the role of host APOBEC genes, which have an important role in molecular editing including in the response to the viral DNA and their role in HPV-driven carcinogenesis. Further, we also discuss data developed suggesting the existence of HPV-derived miRNAs in HPV + tumors and their potential role in regulating the host transcriptome. Collectively, while recent advances in these two areas have added complexity to the working model of papillomavirus-induced oncogenesis, these discoveries have also shed a light onto new areas of research that will be required to fully understand the process.

Ureaplasma parvum (U. parvum) is generally regarded as innocuous, and studies focusing on variations in pathogenicity among U. parvum serovars are inadequate. We elucidated the variations in the pathogenicity of U. parvum serovars in promoting human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN).

This cross-sectional study used baseline data from a Chinese multicenter prospective cohort of women of childbearing age undergoing routine cervical cancer screening. We employed multivariate logistic regression analysis to estimate the pathogenic effects of specific U. parvum serovars on HPV infection and CIN. Causal mediation analysis was performed to ascertain the direct effects of specific U. parvum serovars on CIN and their indirect implications via HPV infection.

The final data analysis encompassed 7058 participants. Upon adjusting for confounding factors, a positive association was observed between U. parvum serovars 1, 3, and 6 and HPV infection (OR 1.53, 95%CI 1.15-2.03; OR 1.31, 95%CI 1.06-1.64; OR 2.34, 95%CI 1.90-2.87); however, only participants with U. parvum serovar 6 showed an increased risk of CIN (OR 1.90, 95%CI 1.19-3.02). No substantial correlation was observed between U. parvum serovar 14 and HPV or CIN incidence. HPV infection potentially mediates the influence of U. parvum serovar 6 on CIN, with a mediation proportion of 76.66%.

Our findings suggest that different U. parvum serovars vary in pathogenicity regarding HPV and CIN. Early detection of specific U. parvum serovars, such as U. parvum serovar 6, in HPV-infected individuals may enable early intervention therapies and reduce the risk of CIN development.

Inflammatory bowel disease (IBD) has been reported to be associated with risk of uterine cervical neoplasm. We aimed to evaluate the causal relationship between IBD and uterine cervical neoplasm using a bidirectional Mendelian randomization analysis.

We derived instrumental variables for IBD, including Crohn's disease and ulcerative colitis, from the IEU Open genome-wide association study (GWAS) database, and for the histological subtypes of uterine cervical neoplasm from the FinnGen repository's GWAS data. The collected GWAS data predominantly represent individuals of European ancestry. The inverse-variance weighted (IVW) method was employed as primary analysis approach.

IBD (IVW odds ratio = 1.127, 95% confidence interval = 1.016-1.251; p = 0.024) and CD (IVW odds ratio = 1.119, 95% confidence interval = 1.023-1.224; p = 0.014) exhibited a significant causal effect on malignant cervical carcinoma. Sensitivity analyses confirmed these findings.

Genetically predicted IBD and CD are risk factors for the development of malignant cervical carcinoma. Patients with IBD and CD require specific attention to prevent cervical squamous cell carcinoma. Further studies to elucidate the underlying mechanisms may reveal new therapeutic targets.