Please select the outcome measures that correspond to the clinical trial below.
Title: A Long-term Follow-up Registry-based Cohort Study of HPV Vaccine Efficacy Against Cervical Pre-cancerous Lesions and Cervical Cancers in a Cohort of Females Previously Enrolled From Finland in Study HPV-008, as Compared to a Non-intervention Population -Based Reference Cohort of Females From Finland
Brief 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.


Options:
A: Demonstration of lot-to-lot consistency in terms of immunogenicity of 3 lots of HPV-16/18 vaccine.; Demonstration of non-inferiority in terms of immunogenicity of the HPV vaccine produced with a revised manufacturing process compared to the HPV vaccine produced with a previous manufacturing process
B: Occurrence of intraepithelial neoplasia grade 3 or worse (CIN3+). including CIN3, cervical cancer (squamous cell carcinoma or adenocarcinoma). (The time frame is up to 15 years (for the interim analyses: 4, 7 and 10 years). (Start and end of passive follow-up, Cohorts A and B: 01.01.2010 - 31.12. 2024; Cohorts C1 and C2: 01.10.2007/01.10.2008 - 30.09.2021/30.09.2023.))
C: To determine the HPV-type specific antibody levels at 2, 3.5, and 5 years after completion of the QHPV vaccine schedule for each of the arms in P1047 (208 weeks (4 Years))
D: Measurable antibody mediated neutralisation of HPV serotype 6, 11, 16, 18 and genetically related serotypes, especially 45 (18 months from enrollment)

Answer: B