Attack rates of human papillomavirus type 16 and cervical neoplasia in primiparous women and field trial designs for HPV16 vaccination

Background: Identification of human papillomavirus type 16 (HPV16) as the m ajor risk factor for cervical neoplasia, and mass production of DNA free HP V capsids have paved the way to preventive vaccination trials. Design of su ch trials requires reliable attack rate data. Objective: Determination of (1) HPV16 and (2) cervical neoplasia attack rat es in primiparous women. Estimation of actuarial sample sizes for HPV16 vac cination phase IV trials. Design: A longitudinal cohort study. Methods: Population based Finnish Maternity Cohort (FMC) and Finnish Cancer Registry (FCR) were linked for the identification of two cohorts of primip arous women: (1) a random subsample of the FMC: 1656 women with two pregnan cies between 1983-9 or 1990-6 and living in the Helsinki metropolitan area, and (2) all 72 791 primiparous women living in the same area during 1983-9 4. Attack rate for persistent HPV16 infection (1) was estimated in 1279 ser onegative women by proportion of seroconversions between the first and the second pregnancy. Comparable 10 year cumulative incidence rate (CR) of cerv ical intraepithelial neoplasia grade III and cervical cancer (CIN III+) (2) was estimated based on cases registered at the FCR during 1991-4. Results: The HPV16 attack rates were 13.8% (<18 years), 7.0% (18-19 years), 2.3% (21 years), 2.4% (23 years), and 4.5% (<25 years). Number of vaccinee s required for a 5 year efficacy trial with persistent HPV16 infection as t he end point ranged between 1000 and 3900, assuming 80% power, 90%-70% vacc ine efficacy (VE), and misclassification. The CRs of CIN III+ were 0.33% (< 18 years), 0.44% (18-19 years), 0.21% (20-24 years), and 0.28% (<25 years). Number of vaccinees required for a 10 year efficacy trial with HPV16 posit ive; CIN III+ as the end point was 15 000 assuming 80% power, 90% VE, and 7 5% aetiological fraction of CIN III+ for HPV16. Conclusions: The attack rates of HPV16 and CIN III+ identify primiparous wo men under 25 years of age among target populations for postnatal HPV vaccin ation at phase II/III trials.