Options for design of real-world impact studies of single-dose vaccine schedules

Based on existing evidence for efficacy, savings, and advantages in delivery, some countries may elect to pilot or roll out single-dose human papillomavirus (HPV) vaccination (instead of, or in combination with, two-dose) in advance of a WHO policy decision. Accelerated evidence of population-based effectiveness (hereafter referred to as overall effectiveness, OE) of one-dose vaccine programs could be gained through regular surveys of HPV prevalence in young women before and after vaccination introduction. In order to offer the earliest information on OE, one-dose HPV vaccination should target one or more birth cohorts as close as possible to the age when sexual activity most often starts in a given population. A catch-up one-dose vaccination program of girls up to 18 years of age who would have been too old to profit from the introduction of a routine HPV vaccination program in preadolescents would minimize the interval between vaccination and the possibility to monitor vaccination impact in young women. In addition, catch-up is especially desirable in low- and middle-income countries with little access to screening as "missed" cohorts may face high risk of cervical cancer death. HPV prevalence should be firstly monitored in age groups of women who may already be sexually active but still reluctant to admit it and to accept vaginal examination for the collection of cervical cells. Hence, HPV testing from urine samples, for which good concordance with cervical cells has been proven, offers a feasible approach to assess periodically vaccine OE in representative samples of 17-20 year-old women. This type of observational study would greatly benefit from the presence of a population census and the creation of a vaccination registry. A real-world demonstration of OE of the new schedule would complement the findings of ongoing clinical trials and immunogenicity studies on the efficacy of single-dose HPV vaccination.