The quality of life of frequently vs. infrequently screened HPV vaccinated women.

PURPOSE: Cervical lesions caused by human papillomavirus (HPV) are related to decreased quality of life (QoL) of women. Also, cervical cancer (CC) screening can cause psychological adverse effects. It has been assumed that by decreasing the HPV-related disease burden, HPV vaccinations would increase the QoL. This study compares the effect of CC screening on QoL of HPV vaccinated women in two different screening protocols. METHODS: A total of 753 HPV16/18 vaccinated women were randomized to frequent (22/25/28 years of age) and infrequent (28 years of age) CC screening arms. QoL questionnaires (EQ VAS, RAND 36, amended CECA 10) were sent at the age of 28. RESULTS: Median EQ VAS scores were 80 (Q1-Q3 75-90) in both screening arms. Mean RAND 36 scores of frequently and infrequently screened women were 78.13/81.64 in Physical role functioning domain and, respectively, 77.93/80.18 in Pain, 69.10/69.12 in General Health, 54.67/53.61 in Energy, 83.72/85.11 in Social functioning, 69.53/69.68 in Emotional role functioning, and 68.16/69.29 in Emotional well-being domain. Among women with a self-reported history of Pap cytology abnormalities, overall mean scores of amended CECA 10 were 69.52/72.07, and among women with a self-reported history of genital warts, 60.09/66.73, respectively. CONCLUSION: There was no significant difference in the QoL of HPV vaccinated women between the two CC screening arms. Women were mostly satisfied with the screening experience despite the screening frequency. This information is important for the future screening program planning as we need to reach the best possible balance with screening benefits and harms. TRIAL REGISTRATION NUMBER: NCT02149030, date of registration 29/5/2014.

Baseline findings and safety of infrequent vs. frequent screening of human papillomavirus vaccinated women.

Less frequent cervical cancer screening in human papillomavirus (HPV) vaccinated birth cohorts could produce considerable savings without increasing cervical cancer incidence and loss of life-years. We report here the baseline findings and interim results of safety and accuracy of infrequent screening among HPV16/18 vaccinated females. The entire 1992-1994 birth-cohorts (30,139 females) were invited to a community-randomized HPV16/18-vaccination trial. A total of 9,482 female trial participants received HPV16/18-vaccination in 2007-2009 at age of 13-15. At age 22, 4,273 (45%) of these females consented to attend a randomized trial on frequent (ages 22/25/28; Arm 1: 2,073 females) vs. infrequent screening (age 28; Arm 2: 2,200 females) in 2014-2017. Females (1,329), who had got HPV16/18 vaccination at age 18 comprised the safety Arm 3. Baseline prevalence and incidence of HPV16/18 and other high-risk HPV types were: 0.5% (53/1,000 follow-up years, 104 ) and 25% (2,530/104 ) in the frequently screened Arm 1; 0.2% (23/104 ) and 24% (2,413/104 ) in the infrequently screened Arm 2; and 3.1% (304/104 ) and 23% (2,284/104 ) in the safety Arm 3. Corresponding prevalence of HSIL/ASC-H and of any abnormal cytological findings were: 0.3 and 4.2% (Arm 1), 0.4 and 5.3% (Arm 2) and 0.3 and 4.7% (Arm 3). Equally rare HSIL/CIN3 findings in the infrequently screened safety Arm A3 (0.4%) and in the frequently screened Arm 1 (0.4%) indicate no safety concerns on infrequent screening despite the up to 10 times higher HPV16/18 baseline prevalence and incidence in the former.

Head-to-head comparison of two human papillomavirus vaccines for efficacy against cervical intraepithelial neoplasia grade 3 and adenocarcinoma in situ-population-based follow-up of two cluster-randomized trials.

Introduction: We report head-to-head comparison of the bivalent and quadrivalent HPV vaccine efficacies against immediate precursors of cervical cancer from 15 years' country-wide cancer registry follow-up of phase III trial cohorts and an age-aligned cohort of unvaccinated women. Methods: These individually and/or clusterrandomized cohorts of HPV6/11/16/18- and HPV16/18-vaccinated and unvaccinated women were enrolled, respectively, in 2002, 2004, and 2003/2005. The trial cohorts comprised initially 16- to 17-year-old HPV6/11/16/18-vaccinated FUTURE II (NCT00092534) participants (866) and HPV16/18-vaccinated PATRICIA (NCT00122681) and 012 trial (NCT00169494) participants (2,465), and 16,526 initially 16- to 19-year-old unvaccinated controls. After active 4-year clinical follow-up, passive, country-wide Finnish Cancer Registry (FCR) follow-up for cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS) was based on consented use of unique personal identifiers and started 6 months after the end of the FUTURE II and PATRICIA trials in 2007 and 2009, and ended at the end of 2019. The follow-up with altogether 229,020 follow-up years was age-aligned to ensure that similarly aged cohorts were passively followed up for 15 years post=vaccination for the intention-to-treat analyses of vaccine efficacy. Results: Overall, we identified 5 and 16 CIN3 (no AIS) cases in the HPV6/11/16/18 and HPV16/18 cohorts, respectively, during the FCR-based follow-up. In the unvaccinated cohort, we identified 281 CIN3 cases, 20 AIS cases, and 13 cases with invasive cervical cancer. Vaccine efficacies against CIN3+ were 68.4% and 64.5% for the quadrivalent and the bivalent vaccines, respectively, with overlapping confidence intervals. Discussion: Long-term follow-up of randomized, initially adolescent HPV-vaccinated and unvaccinated cohorts shows, in this head-to-head setting, that the bivalent and quadrivalent HPV vaccines are equally effective against immediate precursors of cervical cancer.

Human papillomavirus vaccine efficacy against invasive, HPV-positive cancers: population-based follow-up of a cluster-randomised trial.

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.