Search

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., Competing Interests: Competing interests: ML and DA have grants from Merck & Co Inc and GSK for HPV vaccination trials through their employers (Tampere University, ML; Family Federation Finland, DA)., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Human papillomavirus (HPV) vaccination protects against HPV, a necessary risk factor for cervical cancer. We now report results from population-based follow-up of randomised cohorts that vaccination provides HPV-type-specific protection against invasive cancer., Methods: Individually and/or cluster randomised cohorts of HPV-vaccinated and non-vaccinated women were enrolled in 2002-2005. HPV vaccine cohorts comprised originally 16-17 year-old HPV 16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2465) and HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866). Altogether, 3341 vaccines were followed by the Finnish Cancer Registry in the same way as 16 526 non-HPV-vaccinated controls. The control cohort stemmed from 15 665 originally 18-19 years-old women enrolled in 2003 (6499) or 2005 (9166) and 861 placebo recipients of the FUTURE II trial. The follow-up started 6 months after the clinical trials in 2007 and 2009 and ended in 2019. It was age aligned for the cohorts., Findings: During a follow-up time of up to 11 years, we identified 17 HPV-positive invasive cancer cases (14 cervical cancers, 1 vaginal cancer, 1 vulvar cancer and 1 tongue cancer) in the non-HPV-vaccinated cohorts and no cases in the HPV-vaccinated cohorts. HPV typing of diagnostic tumour blocks found HPV16 in nine cervical cancer cases, HPV18, HPV33 and HPV52 each in two cases and HPV45 in one cervical cancer case. The vaginal, vulvar and tongue cancer cases were, respectively, positive for HPV16, HPV52/66 and HPV213. Intention-to-treat vaccine efficacy against all HPV-positive cancers was 100% (95% CI 2 to 100, p<0.05)., Interpretation: Vaccination is effective against invasive HPV-positive cancer., Trial Registration Number: NCT00122681, Post-results; NCT00169494, Post-results; NCT00092534, Post-results., Competing Interests: Competing interests: We declare that ML, DA, JD and JPaa have received grants from Merck & Co. Inc. and/or from the GSK group of companies through their respective employers. GSK Biologicals SA was provided the opportunity to review this manuscript but the authors are solely responsible for final content and interpretation., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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. Chlamydia trachomatis 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., Competing Interests: Competing interests: ML and DA have grants from Merck & Co. Inc. and GSK for HPV vaccination trials through their employers (Tampere University, ML; Family Federation Finland, DA)., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Due to long lag time between infection/cancer diagnoses human papillomavirus (HPV) vaccination programs will deliver vaccine efficacy (VE) estimates against cancer end-points late. Cancer registry follow-up of population-based, randomised trial cohorts of vaccinated and unvaccinated women was undertaken for the estimation of VE against cervical intraepithelial neoplasia grade three and invasive cancer (CIN3+)., Methods: We report interim results with 98 561 person years of Finnish Cancer Registry -based follow-up of individually and/or cluster randomised cohorts of HPV-16/18 vaccinated and unvaccinated adolescent women enrolled in June 2003/2005, and between May 2004 and April 2005, respectively. The cohorts comprised 15 627 18- to 19-year-old unvaccinated women (NCT01393470), and 2 401 and 64 16- to 17-year-old HPV-16/18 vaccinated women participating the PATRICIA (NCT00122681) and HPV-012 (NCT00169494) trials, respectively. The age-aligned passive follow-up started 6 months after the clinical trials' end., Results: During the follow-up of 4.5 to 10 years post enrolment we identified 75 cases of cervical intraepithelial neoplasia grade 3 (CIN3) and 4 cases of invasive cervical cancer (ICC) in the unvaccinated cohort, and 4 CIN3 cases in the HPV-16/18 vaccinated women. Diagnostic blocks were available for HPV typing from 87% of the cases. CIN3+ lesions were detectable in 54 cases. HPV16 was found in 26 of 50 unvaccinated CIN3+ cases, and in 3 CIN3+ cases in the HPV-16/18 vaccinated women. The latter were all baseline positive for cervical HPV16 DNA. Baseline data was not available for the unvaccinated women. Intention-to-treat VE against any CIN3+ was 66% (95% CI 8, 88)., Conclusions: Ten years post vaccination the AS04-adjuvanted HPV-16/18 vaccine shows continued efficacy against CIN3+ irrespectively of HPV type. Vaccine efficacy was not observed in baseline HPV16 DNA positive subjects., Trial Registration Number: NCT01393470., Competing Interests: Competing interests: DA, ML, JP and JD have received grants from GSK group of companies and/or Merck & Co. Inc. through their employers (DA, Family Federation Finland; ML; University of Tampere; JP and PN University of Helsinki; JD and ML, Karolinska Institute) for HPV vaccination studies. GD was and FS is employee of GSK group of companies. FS has received shares and stock options from the GSK group of companies., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)