Background:

Evaluating the impact/effectiveness of human papillomavirus (HPV) vaccination generally assumes stability in factors driving transmission, which might not be valid. We aimed to develop, validate, and test a grouping of non-vaccine–preventable HPV (NVP-HPV) types as a molecular indicator associated with sexual behaviors to control for changes in HPV transmission risk.

Methods:

We used data from the National Surveys of Sexual Attitudes and Lifestyles (Natsal-2, 1999–2001, N = 1,849; Natsal-3, 2010–2012, N = 2,407) to validate the association of NVP-HPV (26/53/66/70/73) with self-reported sexual behaviors. We calculated NVP-HPV–adjusted HPV16/18 vaccine impact/effectiveness estimates in two real-world scenarios: Natsal-2/Natsal-3 (sexually experienced women in Britain, 18–44 years), and England’s HPV surveillance (women, 16–24 years; 2008, N = 3,539; 2010–2020, N = 24,707). Samples (urine/vulvovaginal swabs) were tested for 21 HPV genotypes (6/11/16/18/26/31/33/35/39/45/51/52/53/56/58/59/66/68/70/73/82) using an in-house multiplex PCR and Luminex-based genotyping assay.

Results:

NVP-HPV infection was strongly associated with sexual behaviors (e.g., younger age at sexual debut and numbers of partners). In Natsal data, adjusting for NVP-HPV did not change vaccine impact estimates [unadjusted prevalence ratio (PR): 0.50 (0.27–0.95) and adjusted PR: 0.45 (0.25–0.82)]. In the second scenario, adjusting for NVP-HPV did not change the PR for HPV 16/18 when comparing 2020 with 2010 [0.07 (0.03–0.15), unadjusted and adjusted PR]. In both scenarios, the prevalence of NVP-HPV did not change over time.

Conclusions:

We have demonstrated proof of concept that NVP-HPV is strongly associated with sexual behaviors. Adjusting for NVP-HPV in two datasets found that the original estimates were robust.

Impact:

NVP-HPV might be used to control for changes in HPV transmission risk over time and between groups when evaluating vaccination impact/effectiveness.

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