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. 2025 Jul 1;117(7):1377-1386.
doi: 10.1093/jnci/djaf055.

HPV vaccine impact: genotype-specific changes in cervical pre-cancer share similarities with changes in cervical screening cytology

Rachael Adcock  1 , Cosette M Wheeler  1   2 , William C Hunt  1 , Norah E Torrez-Martinez  1 , Michael Robertson  1 , Ruth McDonald  1 , Nancy E Joste  2 , Mark H Stoler  3 , Maurits N C de Koning  4 , Wim G V Quint  4 ; New Mexico HPV Pap Registry Steering Committee Members
Collaborators, Affiliations

HPV vaccine impact: genotype-specific changes in cervical pre-cancer share similarities with changes in cervical screening cytology

Rachael Adcock et al. J Natl Cancer Inst. .

Abstract

Background: After human papillomavirus (HPV) vaccine introduction, declines in the prevalence of HPV vaccine types have been observed in screening cytology, but data from the United States describing HPV type-specific changes in cervical intraepithelial neoplasia (CIN) grades 2-3 and adenocarcinoma in situ (CIN2/CIN3/AIS) are limited.

Methods: A statewide sample of individuals with cervical biopsies was selected for broad-spectrum HPV genotyping. CIN2/CIN3/AIS incidence and prevalence were calculated for type-specific high-risk HPV (hrHPV) among individuals aged 15-29 years. Weighted incidence rate ratios (IRR) and relative differences in prevalence (RDP) were computed to compare 3 time periods: 2006-2009 (Cohort 1 [C1], n = 4121), 2012-2015 (C2, n = 2194), and 2015-2018 (C3, n = 1481).

Results: When comparing C1 vs C3 among those aged 21-25 years, statistically significant reductions in hrHPV type-specific CIN2/CIN3/AIS incidence were observed for HPV16, HPV18, HPV31, and HPV33, with corresponding IRRs of 0.4 (95% confidence interval [95% CI] = 0.3 to 0.4), 0.3 (95% CI = 0.1 to 0.7), 0.6 (95% CI = 0.5 to 0.9), and 0.4 (95% CI = 0.1 to 0.8), respectively. The RDP comparing C1 vs C3 for HPV16/18-positive CIN2/CIN3/AIS was -43.8% (P < .001). When excluding HPV16/18 or HPV16/18/31/33 from all hrHPV types, the RDP was +56.6% and +92.5% (P < .001), respectively.

Conclusions: hrHPV type-specific CIN2/CIN3/AIS incidence decreased with statistical significance for vaccine types HPV16/18 and for HPV31 and HPV33. Although the HPV vaccine is highly beneficial and a top priority for preventing HPV-related cancer, the long-term vaccine impact in cohorts receiving the 4-valent HPV vaccine requires continued follow-up to assess genotype-specific distributions in the remaining CIN2+ lesions and cancers.

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Conflict of interest statement

C.M.W. and J.C. have received funds from grants, cooperative agreements, or subcontracts related to cervical screening and triage through their respective institution, the University of New Mexico Health Sciences Center and Queen Mary University London. C.M.W. reports receiving reagents and equipment from Roche Molecular Systems, Roche/Ventana Medical Systems, and Hologic through her institution and outside of the submitted work, and research support from Hologic and Becton Dickinson (BD), also outside of this work. J.C. reports being on the speaker’s bureau for Hologic and BD and the data monitoring committee for a Roche liver cancer trial. M.K. has received grants from Viroclinics-DDL (a Cerba Research company) outside the work of the current study. M.H.S. is a consultant in clinical trial development and performance and/or an expert pathologist in clinical trials for Merck, Roche/Ventana Medical Systems, Becton Dickinson (BD) Life Sciences, Abbott Molecular, Inovio Pharmaceuticals, and Frantz Viral Therapeutics. All other authors and NMHPVPR Steering Committee members have nothing to disclose.

Figures

Figure 1.
Figure 1.
HPV type-specific incidence by year (2006-2018) among those aged 21-25 years with CIN2/CIN3/AIS. Data weighted to represent the statewide population of individuals with cervical biopsies. No data available for 2010/2011. Different scales used for type-specific incidence of HPV16 and 18 versus HPV31 and 33. Line graphs showing the trend in incidence of HPV type-specific infections between the years 2006 and 2018 for individuals aged 21-25 years with CIN2/CIN3/AIS excluding cancer. HPV types plotted were HPV16 and 18, and HPV31 and 33. Different scales were used for type-specific incidence of HPV16 and 18 versus HPV31 and 33. No data were available for the years 2010/2011 because they fell outside the cohorts for inclusion. Abbreviations: HPV = human papillomavirus; CIN2 = cervical intraepithelial neoplasia [CIN] grade 2; CIN3 = CIN grade 3; AIS = adenocarcinoma in situ.
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