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Non–Vaccine-Type Human Papillomavirus Prevalence After Vaccine Introduction: No Evidence for Type Replacement but Evidence for Cross-Protection

Saccucci, Mónica, BS*; Franco, Eduardo, L., DrPH; Ding, Lili, PhD*‡; Bernstein, David, I., MD, MA*‡; Brown, Darron, MD, MPH§; Kahn, Jessica, A., MD, MPH*‡

Sexually Transmitted Diseases: April 2018 - Volume 45 - Issue 4 - p 260–265
doi: 10.1097/OLQ.0000000000000731
Original Studies

Background We examined non–vaccine-type human papillomavirus (HPV) prevalence in a community before and during the first 8 years after vaccine introduction, to assess for (1) type replacement with any non–vaccine-type HPV and (2) cross-protection with non–vaccine types genetically related to vaccine-type HPV.

Methods Sexually experienced 13- to- 26-year-old women were recruited for 3 cross-sectional studies from 2006 to 2014 (N = 1180). Outcome variables were as follows: (1) prevalence of at least 1 of 32 anogenital non–vaccine-type HPVs and (2) prevalence of at least 1 HPV type genetically related to HPV-16 and HPV-18. We determined changes in proportions of non–vaccine-type HPV prevalence across the study waves using logistic regression with propensity score inverse probability weighting.

Results Vaccine initiation rates increased from 0% to 71.3%. Logistic regression demonstrated that from 2006 to 2014, there was no increase in non–vaccine-type HPV among vaccinated women (adjusted odds ratio [AOR], 1.02; 95% confidence interval [CI], 0.73–1.42), but an increase among unvaccinated women (AOR, 1.88; 95% CI, 1.16–3.04). Conversely, there was a decrease in types genetically related to HPV-16 among vaccinated (AOR, 0.57; 95% CI, 0.38–0.88) but not unvaccinated women (AOR, 1.33; 95% CI, 0.81–2.17).

Conclusions We did not find evidence of type replacement, but did find evidence of cross-protection against types genetically related to HPV-16. These findings have implications for cost-effectiveness analyses, which may impact vaccine-related policies, and provide information to assess the differential risk for cervical cancer in unvaccinated and vaccinated women, which may influence clinical screening recommendations. The findings also have implications for public health programs, such as health messaging for adolescents, parents, and clinicians about HPV vaccination.

Surveillance studies of young women during the 8 years after human papillomavirus vaccine introduction did not demonstrate evidence of type replacement, but did demonstrate cross-protection against types genetically related to human papillomavirus type 16.

From the *University of Cincinnati College of Medicine, Cincinnati, OH; †McGill University, Montreal, Quebec, Canada; ‡Cincinnati Children's Hospital Medical Center, Cincinnati, OH; and §Indiana University School of Medicine, Indianapolis, IN

Acknowledgments: The authors thank the Clinical Research Coordinators (Lisa Higgins, RPh; Charlene Morrow, RN, MSN; and Rachel Thomas, MS) and staff of the Teen Health Center and Cincinnati Health Department for their assistance with this research study.

Conflict of Interest and Sources of Funding: Dr Kahn has co-chaired 2 National Institutes of Health–funded human papillomavirus (HPV) vaccine clinical trials in HIV-infected individuals, for which Merck & Co, Inc, provided vaccine and immunogenicity titers. Dr Franco has served as occasional advisor to companies involved with HPV vaccination (Merck, GSK) and HPV and cervical cancer diagnostics (Roche, BD, Qiagen). His institution has received unconditional funding from Merck for investigator-initiated studies carried out in his unit. Dr Brown has received honoraria and grant support from Merck, and his institution Indiana University and Merck have a confidential agreement that pays the university based on certain landmarks of vaccine development; Dr Brown receives a portion of this money as income. For the remaining authors, no competing financial interests exist.

This work was supported by grants from the US National Institutes of Health, National Institute of Allergy and Infectious Diseases (R01 AI073713 and R01 AI104709) and by a U.S. National Institutes of Health, Medical Student Summer Research Program Training Grant (T35 DK 060444).

Correspondence: Jessica Kahn, MD, MPH, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, MLC 4000, Cincinnati, OH 45229. E-mail:

Received for publication July 7, 2017, and accepted September 27, 2017.

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