Update on human papillomavirus vaccination: Where are we now?

Table 1 Phase III efficacy in women

	Future I	Future II	Patricia	CVT	Broad spectrum HPV vaccine study
Vaccine	Gardasil®	Gardasil®	Cervarix®	Cervarix®	Gardasil9®
Funding	Merck and Co., Inc.	Merck and Co., Inc.	GlaxoSmithKline	National Cancer Inst.	Merck and Co., Inc.
Number enrolled	6463	12167	18729	7466	14215
Number of countries	16	13	14	1	14
Duration of trial	4 yr	4 yr	4 yr	4 yr	4 yr
Age (yr)	16-24	15-26	15-25	18-25
Lifetime sexual partners	< 4	< 4	< 6	No restriction	< 4
Exclusions	Pregnancy, history of abnormal Pap smear or genital warts	Pregnancy, history of abnormal Pap smear	Pregnancy, breastfeeding, history of colposcopy, autoimmune disease/immunodeficiency, HPV 16/18-associated CIN2+ at enrollment	Pregnancy, breastfeeding, history of immunosuppression, hysterectomy, hepatitis A vaccination	Prior abnormal Pap smear, > 4 lifetime sexual partners, no prior abnormal finding on cervical biopsy
Primary endpoint	Incidence of vaccine-type HPV associated CIN1-3, AIS or cancer, combined incidence of vaccine-type HPV associated anogenital warts, VIN/VaIN1-3 or cancer	HPV 16 or 18 associated CIN2/3	Incidence of HPV 16 or 18 CIN2 or greater	HPV 16 or 18 persistent infection (12 mos.) or HPV 16 or 18 associated CIN2+	High-grade cervical, vulvar, and vaginal disease
Mean follow-up time	3 yr	3 yr	14.8 mo
Immunogenicity	99.5% seroconversion after 3 doses	99% seroconversion to vaccine-associated HPV types	99.5% seroconversion rates in women aged 15-25 yr		Non-inferior to quadrivalent vaccine

CVT: Costa Rica HPV Vaccine Trials; HPV: Human papillomavirus; VIN/VaIN: Vulvar/vaginal intraepithelial neoplasia.

Table 2 Worldwide vaccination protocols

	Country	Vaccine in schedule (as of December 31, 2014)	Year of introduction in entire country	Target population	Schedule
Africa	Botswana	No	2015	Girls 9-13 yr	3 doses
	Lesotho	Yes	2012	9-14 yr	3 doses
	Malawi	No	2015	Girls 9-13 yr	3 doses
	Rwanda	Yes	2011		3 doses
	Seychelles	Yes	2014	Girls 10-12 yr
	South Africa	Yes	2014	9 yr	2 doses
Americas	Argentina	Yes	2011	11 yr	3 doses
	Barbados	Yes	2014	11 yr	2 doses
	Brazil	Yes	2014	9-14 yr	2 doses
	Canada	Yes	2009		3 doses
	Colombia	Yes	2012	9-17 yr	3 doses
	Ecuador	Yes	2014	9 yr	2 doses
	Guyana	Yes	Not available	Special groups	3 doses
	Mexico	Yes	2012	10 yr	2 doses
	Panama	Yes	2008	10 yr	3 doses
	Paraguay	Yes	2013	10 yr	3 doses
	Peru	Yes	2011	10 yr	3 doses
	Suriname	Yes	2013	9 yr
	Trinidad and Tobago	Yes	2013	Females 11-45 yr, males 11-26 yr	3 doses
	United States	Yes	2006	11-26 females, 11-21 males (26 if high risk)	3 doses
	Uruguay	Yes	2013	12 yr	3 doses
Eastern Mediterranean	Bahrain	No
	Libya	Yes	2013	15 yr	3 doses
Europe	Andorra	Yes	2014	12 yr
	Austria	Yes	2008	9 yr	3 doses
	Belgium	Yes	2011	12 yr (13-14 in Wallonia)	3 doses
	Czech Republic (the)	Yes	2012	13 yr
	Denmark	Yes	2007	12 yr	3 doses
	Finland	Yes	2013	11-12 yr
	France	Yes	2006	Girls 11-14 yr	3 doses
	Germany	Yes	2007	Girls 12-17 yr	3 doses
	Greece	Yes	2009	11-18 yr	3 doses
	Hungary	Yes	2014	12 yr
	Iceland	Yes	2011	12 yr	3 doses
	Ireland	Yes	2010	Girls 12-13 yr	3 doses
	Israel	Yes	2010	13 yr (or women 9-45 yr)	3 doses
	Italy	Yes	2009	Girls 12 yr	3 doses
	Latvia	Yes	2010	12 yr	3 doses
	Luxembourg	Yes	2008	12-18 yr
	Malta	Yes	2013	12 yr	3 doses
	Monaco	Yes	2006	14 yr	3 doses
	Netherlands (the)	Yes	2010	12 yr	2 doses
	Norway	Yes	2009	Girls 12 yr	3 doses
	Portugal	Yes	2008	10-13 yr	3 doses
	San Marino	Yes	2008	11 yr
	Slovenia	Yes	2009	11-12 yr	2 doses
	Spain	Yes	2007	12 yr	3 doses
	Sweden	Yes	2010	Girls 10-12 yr	3 doses
	Switzerland	Yes	2006	Girls 11-14 yr	3 doses
	The former Yugoslav Republic of Macedonia	Yes	2009	12 yr	3 doses
	United Kingdom	Yes	2008	12-13 yr	2 doses
	Uzbekistan	No	2015
South-East Asia	Bhutan	Yes	2009	Girls 12 yr	3 doses
Western Pacific	Australia	Yes	2007	10-15 yr
	Brunei Darussalam	Yes	2012	13 yr	3 doses
	Cook Islands	Yes	2011	9 yr
	Fiji	Yes	2013	13 yr
	Japan	Yes	2011	13 yr	3 doses
	Malaysia	Yes	2010	Girls 13 yr	3 doses
	Marshall Islands (the)	Yes	2009	11-12 yr
	Micronesia (Federated States of)	Yes	2010	9 yr	3 doses
	New Zealand	Yes	2009	12 yr (and other eligible individuals)	3 doses
	Palau	Yes	2008	9-26 yr	3 doses
	Philippines (the)				2 doses
	Singapore	Yes	2010	Girls 9-26 yr	3 doses

Table 3 Possible interventions to increase human papillomavirus vaccine uptake

Ref.	Year	Country	Objectives	n	Outcome	Target population	Educational tools
Chapman et al[54]	2010	United States	Evaluation of a video-based educational tool to increase HPV vaccine acceptability	256	Vaccine acceptability increased following intervention	Women aged 18-60	8 min video
Kennedy et al[55]	2011	United States	Improvement of HPV vaccine educational materials and determination of efficacy	411	Increase in likelihood of vaccination of children and favorable view of HPV vaccine	Parents of girls 11-18 yr of age	Educational flyer
Kobetz et al[51]	2011	Haiti	Assessment of women's knowledge and beliefs regarding cervical cancer and HPV		Need for culturally and linguistically appropriate educational initiatives	Haitian immigrant women in Miami, FL	Focus groups
Kester et al[56]	2014	United States	Evaluation of the effects of a brief education session on HPV awareness	131	Higher vaccination intent among intervention group	18-26 yr old females and males	5-10 min education session
Kim[50]	2015	South Korea	Assessment of knowledge of HPV relation to cancer in children	117	HPV education at elementary school would be helpful	Fifth-grade girls and boys	2 h education session
Nodulman et al[57]	2015	United States	Evaluation of feasibility of increased immunization rates through middle school vaccination programs	117	Low acceptance of middle school vaccination by adolescents, parents and stakeholders	Middle school stakeholders, nurses, parents, adolescents, administrators	Middle school vaccination program

HPV: Human papillomavirus.

Table 4 Evaluation of barriers to human papillomavirus vaccination

Ref.	Year	Country	Target population	Objectives	n	Identified barriers to vaccination
Mortensen[46]	2010	Denmark	Women aged 16-26	Evaluation of reasons for acceptance or rejection of HPV vaccine following general vaccine availability	794	Cost, lack of information about the benefits of vaccination, and lack of knowledge about HPV
Ogilvie et al[58]	2010	Canada	Parents with daughters in 6th grade	Determination of parental factors associated with receipt of the HPV vaccine in a publicly funded school-based HPV vaccine program	2025	Lack of knowledge regarding the HPV vaccine
Kobetz et al[51]	2011	United States	Haitian immigrant women in Miami, FL	Assessment of women's knowledge and beliefs regarding cervical cancer and HPV		Lack of education
Jeudin et al[53]	2014	United States	Black and Latina populations	Identification of barriers to uptake of HPV vaccination among low-income and minority girls		Lack of access to primary care, lack of provider recommendation, lack of parental knowledge
Kim[50]	2015	South Korea	Fifth-grade girls and boys	Assessment of children’s knowledge regarding HPV and association with cancer	117	Lack of HPV knowledge, lack of HPV education in schools
Abudukadeer et al[47]	2015	China	Women in Xinjiang province	Assessment of knowledge and perception of cervical cancer	5000	Lack of knowledge about cervical cancer
Blake et al[48]	2015	United States	National Cancer Institute’s 2013 Health Information National Trends Survey Data	Assessment of population knowledge regarding HPV and the HPV vaccine as well as socioeconomic disparities	3185	Lack of HPV awareness and knowledge
Nodulman et al[57]	2015	United States	Middle school stakeholders, nurses, parents, adolescents, administrators	Increase of immunization rates through middle school vaccination programs	117	Lack of knowledge about HPV vaccine

HPV: Human papillomavirus.