Cross-protection and type-replacement over the 17 years after human papillomavirus vaccine introduction in young women

Background The study aim was to examine trends in non-4-valent and non-9-valent vaccine-type HPV detection over the first 17 years after U.S. HPV vaccine introduction among young women. Methods We recruited 13–26 year-old sexually experienced women ( N = 2335) from hospital and community clinics for six surveillance studies from 2006 to 2023, with testing for HPV DNA by Roche Linear Array or TypeSeq2. Outcome variables were: 1) potentially carcinogenic alpha-9 and -7 non-vaccine-type HPV genetically related to HPV16 or 18 but not targeted by the 4- or 9-valent vaccines (to assess for cross-protection) and 2) potentially carcinogenic alpha-5, −6, and − 11 non-vaccine-type HPV not closely genetically related to types targeted by the 4- or 9-valent vaccines (to assess for type replacement). We used inverse probability of treatment weighting with propensity score to balance between-wave differences in participant characteristics in prevalence estimates and in tests of linear trend using surveillance study as a continuous variable. Results Among all, vaccinated, and unvaccinated participants, there were no significant trends in the prevalence of at least 1 non-vaccine-type HPV genetically related to HPV16 and/or HPV18 but not targeted by the 4- or 9-valent vaccines. Positivity for non-vaccine-type HPV genetically unrelated to types targeted by the 4- or 9-valent vaccines remained stable from 2006 to 2015 but increased from 2016 to 2023; the trend was significant for all groups. Conclusions We did not find evidence for cross-protection against types not targeted by the 4-valent or 9-valent vaccines, but did find a signal for possible emerging type replacement.