Long-term follow-up of human papillomavirus type replacement among young pregnant Finnish females before and after a community-randomised HPV vaccination trial with moderate coverage.

Large scale human papillomavirus (HPV) vaccination against the most oncogenic high-risk human papillomavirus (HPV) types 16/18 is rapidly reducing their incidence. However, attempts at assessing if this leads to an increase of nonvaccine targeted HPV types have been hampered by several limitations, such as the inability to differentiate secular trends. We performed a population-based serological survey of unvaccinated young women over 12 years. The women were under 23-years-old, residents from 33 communities which participated in a community-randomised trial (CRT) with approximately 50% vaccination coverage. Serum samples were retrieved pre-CRT and post-CRT implementation. Seropositivity to 17 HPV types was assessed. HPV seroprevalence ratios (PR) comparing the postvaccination to prevaccination era were estimated by trial arm. This was also assessed among the sexual risk-taking core group, where type replacement may occur more rapidly. In total, 8022 serum samples from the population-based Finnish Maternity Cohort were retrieved. HPV types 16/18 showed decreased seroprevalence among the unvaccinated in communities only after gender-neutral vaccination (PR16/18A = 0.8, 95% CI 0.7-0.9). HPV6/11 and HPV73 were decreased after gender-neutral vaccination (PR6/11A = 0.8, 95% CI 0.7-0.9, PR73A = 0.7, 95% CI 0.6-0.9, respectively) and girls-only vaccination (PR6/11B = 0.8, 95% CI 0.7-0.9, PR73B = 0.9, 95% CI 0.8-1.0). HPV68 alone was increased but only after girls-only vaccination (PR68B = 1.3, 95% CI 1.0-1.7, PRcore68B = 2.8, 95% CI 1.2-6.3). A large-scale, long-term follow-up found no type replacement in the communities with the strongest reduction of vaccine HPV types. Limited evidence for an increase in HPV68 was restricted to girls-only vaccinated communities and may have been due to secular trends (ClinicalTrials.gov number: NCT00534638).

The risk of cervical atypia in oral contraceptive users.

BACKGROUND: The interactions of oral contraceptive (OC) use, risk of human papillomavirus (HPV) infection and associated cellular atypia are complex. We investigated the association between history of OC-use, and cytological or histopathological abnormalities in a cohort of non-HPV vaccinated originally 16-17-year-old women participating the PATRICIA trial for 4 years. METHODS: The total number of hepatitis A-virus (control) vaccine recipients participating in the clinical PATRICIA trial in Finland was 2399. Nine-hundred and ninety-nine women returned questionnaires on living conditions-life habits and sexual health after completing the study. Mean age at answering the questionnaire at the end of the clinical trial was 22 years. Age at sexual debut varied between 12 and 16 years for majority of the women. Cervical cytological samples were obtained every 6 months throughout the PATRICIA trial. The relative risk of cervical atypia associated with time since start of oral contraceptives use was calculated as odds ratio (OR) with 95% confidence interval (CI) using logistic regression. RESULTS: Compared to never-users, the smoking and age-at-sexual-debut adjusted relative risk of cervical intraepithelial neoplasia grade 1 (CIN1) in women who had started the use of oral contraceptives for more than 1 year was low (OR 0.2, 95% CI: 0.1-0.7). Risk of cytological atypia was also reduced (OR 0.6) albeit not significantly (95% CI: 0.3-1.3). CONCLUSIONS: Use of oral contraceptives does not increase the risk of cervical atypia but when established might instead be protective.

Association of Chlamydia trachomatis infection with cervical atypia in adolescent women with short-term or long-term use of oral contraceptives: a longitudinal study in HPV vaccinated women.

OBJECTIVE: We assessed the relationship between Chlamydia trachomatis infection, duration of oral contraceptive (OC) use and cervical atypia among young adult Finnish women. DESIGN: A longitudinal study. SETTING AND PARTICIPANTS: Women who were included in this study participated in a community-randomised trial on the effectiveness of human papillomavirus (HPV) vaccination and C. trachomatis screening at ages 18.5 and 22 years in Finland. They completed questionnaires on both visits about sexual behaviours. The cytology test results at age 18.5 and 22 years were also available for those women. The total number of participants in this study at 18.5 years of age were 11 701 and at 22 years of age were 6618. MAIN OUTCOME MEASURE: ORs with 95% CIs using univariable and multivariable logistic regression were used to assess the association between C. trachomatis infection, duration of OC and squamous intraepithelial lesions (SIL). RESULTS: There were 940 cytological SIL cases at the first screening visit and 129 cytological SIL cases at the second screening visit. Among the 22 years old, more than fourfold adjusted risk of SIL was associated with C. trachomatis positivity. The HPV16/18, condom use, smoking and number of sexual partners adjusted joint effect of prolonged OC use and C. trachomatis was significantly increased (OR 4.7, 95% CI 1.7 to 12.8) in the 22-year-old women. This observed joint effect was 1.6 times higher than expected on a multiplicative scale. On additive scale, the observed relative excess risk from interaction was 1.8. CONCLUSION: The risk of SIL in HPV vaccinated women is significantly increased if they are C. trachomatis positive and have used OC for 5 or more years. The biological basis may be lack of condom facilitated protection against sexually transmitted diseases. TRIAL REGISTRATION NUMBER: NCT00534638.

Is the risk of cervical atypia associated with the interval between menarche and the start of sexual activity? A population-based cohort study.

OBJECTIVE: We investigated whether the risk of cervical atypia is associated with a short interval between the age at first sexual intercourse (FSI) or age at the start of oral contraceptive (OC) use and menarche. DESIGN: A population-based cohort study. SETTING: Finnish women in the age range of 16-17 years old were enrolled in the PATRICIA trial of human papillomavirus (HPV) 16/18 vaccine efficacy. PARTICIPANTS: The association of cervical atypia with the interval between FSI or start of OC use and menarche was assessed in the control arm (hepatitis A vaccinated) who had participated in biannual clinical follow-up visits for 4 years. Altogether, 913 women had normal baseline cervical cytology and answered behavioural questionnaires at enrolment and end of the follow-up. MAIN OUTCOME MEASURE: ORs with 95% CIs using univariate and multivariable logistic regression were used to assess the association between cervical atypia and the interval between FSI or the start of OC use and menarche. RESULTS: The mean ages at menarche, FSI and the start of OC use were 12.4, 16.0 and 16.4. Chlamydiatrachomatis infection was associated with an increased risk of cervical atypia in women with a short (<3 years) interval between menarche and FSI/start of OC use (OR 1.8, 95% CI 1.0 to 3.6 and OR 2.2, 95% CI 1.0 to 5.1). Whereas HPV 16/18 infection was associated with increased atypia risk estimates in women with a longer (≥3 years) interval (OR 1.8, 95% CI 1.1 to 2.7 and OR 1.4, 95% CI 1.0 to 2.1). In women with a short interval between menarche and FSI, early age at the start of OC use was not associated with an increased risk of cervical atypia in the univariate (OR 0.7) nor multivariable analyses. CONCLUSION: Short interval between menarche and the age at start of sexual activity does not increase the risk of HPV-associated cervical atypia. TRIAL REGISTRATION NUMBER: NCT00122681.