evaluation of long-term hpv vaccine efficacy

Conditions: Uterine Cervical Cancer

Summary: summary for ethical and practical reasons pre-licensure clinical efficacy phase iii trials for gsk biologicals' hpv-16/18 li vlp as04 vaccine used cervical intraepithelial grade 2 and above (cin2+) lesions as surrogate efficacy endpoint for cervical cancer. the long-term impact of hpv vaccination on cervical cancer as well as other hpv-related non- cervical cancers is, however, an area warranting further exploration in the post-licensure setting. results of the multinational phase iii trial demonstrated high vaccine efficacy against cin2+ associated with hpv-16 and/or hpv-18, significant vaccine efficacy against cin2+ and cin3+ irrespective of hpv type in the lesion as well as evidence of protection against cin2+ associated with hpv types 31 and 45 \[paavonen, et al. 2009\]. over time, vaccinated cohorts should benefit from a substantial reduction in the incidence of cervical cancer considering impact on oncogenic non-vaccine hpv types. this long-term study is conducted to evaluate the long-term impact of gsk biologicals' hpv-16/18 vaccine on the occurrence of cervical pre-cancerous lesions and cervical cancer with the following objectives: * to assess the long-term efficacy of the hpv-16/18 l1 vlp as04 vaccine on the occurrence of cervical cancer including its immediate precursors (cin3+): cervical intraepithelial neoplasia grade 3 (cin3) and adenocarcinoma in situ (ais) by comparing cohorts a and c (see below). * to assess the efficacy of hpv-16/18 l1 vlp as04 vaccine on the occurrence of the following potentially hpv related non-cervical cancers such as vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, anogenital neoplasia and oropharyngeal neoplasia by comparing cohorts a and c (see below) * to assess as an explanatory objective the occurrence of cin3+ breakthrough cases associated with hpv-16 or hpv-18 infection in subjects vaccinated with hpv-16/18 l1 vlp as04 vaccine by close surveillance of cohorts and cross vaccinated cohort b (see below) this prospective, observational cohort study is undertaken in originally 16-17 year-old finnish females who have participated in the gsk biologicals' hpv-008 trial (nct00122681) with regular clinical follow-up, and can be divided in cohort a: female subjects from finland who received hpv-16/18 l1 vlp as04 vaccine in the hpv-008 study between may 2004 and may 2005 (n=2409), and cohort b: female subjects from finland who received the hepatitis a control vaccine in the hpv-008 study (n=2399). all subjects were offered the hpv-16/18 l1 vlp as04 vaccine or screening for cervical cancer at the end of the study (age 21-22): 50% of the subjects, chose not to take cross-over hpv vaccination at hpv-008 study end. referent cohort c: a population-based reference cohort of female subjects from finland who have not been exposed to any hpv vaccine (either during a hpv vaccine trial, or commercially available vaccine; i.e. cervarix or gardasil), enrolled in this study in may - september 2003 or may - september 2005, altogether 15536 subjects). prospective data collection will start at the hpv screening invitation for each subject in 2013. several analyses are planned including an analysis at 8 years post-completion of the hpv-008 study (by 2020) and will provide a total evaluation time of approximately 15 years since first vaccination in the cohort a. the study is self-contained for the primary and secondary endpoints. data from the hpv-008 trial will be used to address exploratory objectives mentioned above. data collection will be performed using the databases from the university of tampere.


Eligibility criteria:
inclusion criteria: * trial cohort (16-17 years at baseline) - the cohort of finnish subjects who participated in the gsk biologicals' hpv-008 trial (nct00122681): * cohort a: subjects who received hpv-16/18 l1 vlp as04 vaccine between may 2004 and may 2005. * cohort b: subjects who received the hepatitis a control vaccine. all subjects were offered the hpv-16/18 l1 vlp as04 vaccine at the end of the study (age 21-22). * cohort b1: subjects who received the hepatitis a control vaccine and then received cross-over hpv vaccination at hpv-008 study end. * cohort b2: subjects who received the hepatitis a control vaccine and who did not receive cross-over hpv vaccination at hpv-008 study end. * referent cohort (18-19 years at baseline): * cohort c: a population-based reference cohort of female subjects from finland who have not been exposed to any hpv vaccine enrolled in this study in may 2005, immediately after recruitment of the hpv-008 clinical trial subjects had been stopped (approximately 9,000 subjects). exclusion criteria: * trial cohort (cohort a and b): previous or planned administration of an hpv vaccine not foreseen by the hpv-008 study protocol or any hpv-008 extension study protocol (gardasil or any experimental hpv vaccine). * referent cohort (cohort c): previous or planned administration of an hpv vaccine (cervarix, gardasil or any experimental hpv vaccine).

Keywords: hpv vaccine long-term efficacy registry-based study evaluation of long-term hpv vaccine efficacy: a population-based, registry-based cohort study in finland.