Please select the eligibility criteria 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: Inclusion Criteria:

* A woman between, and including, 10 and 25 years of age at the time of the first vaccination.
* Written informed consent from the subject prior to enrolment.
* Subject must be free of obvious health problems.
* Subject must have negative urine pregnancy test.

Exclusion Criteria:

* Pregnant or breastfeeding.
* Known acute or chronic, clinically significant pulmonary, cardiovascular, neurologic, hepatic or renal functional abnormality.
* History of chronic condition(s) requiring treatment such as cancer, chronic hepatitis or kidney disease(s), diabetes, or autoimmune disease.
* Previous vaccination against human papillomavirus (HPV).
B: 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).
C: Inclusion Criteria:

* Previous enrollment in P1047
* Completion of the P1047 scheduled vaccine doses for their designated arm.
* Parent or legal guardian able and willing to provide signed informed consent
* Subjects should be between 1 and 2 years following their last HPV vaccination.

Exclusion Criteria:

* Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise the outcome of this study.
* Administration of a globulin-containing product within 90 days prior to enrollment.
* Receipt of an additional dose of Merck HPV vaccine other than that administered for the P1047 study.
* Receipt of GSK HPV vaccine.
D: Inclusion Criteria:

* Aged between 13 and 15 years at the time of the first immunisation
* Female
* No contraindications to vaccination as specified in the "Green Book" - Immunisation Against Infectious Disease, HMSO.
* Written informed consent obtained from parent or guardian of subject

Exclusion Criteria:

* Pregnant or become pregnant during the course of the trial (no contraindications to vaccination for those taking the contraceptive pill).
* Breast-feeding mothers
* Allergic to vaccine components

Answer: B