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Non-Vaccine-Type HPV Prevalence after Vaccine Introduction: No Evidence for Type Replacement but Evidence for Cross-Protection

Saccucci, Mónica BS1; Franco, Eduardo L. PhD2; Ding, Lili PhD1,3; Bernstein, David I. MD, MA1,3; Brown, Darron MD4; Kahn, Jessica A. MD, MPH1,3

doi: 10.1097/OLQ.0000000000000731
Original Study: PDF Only

Background We examined non-vaccine-type HPV prevalence in a community before and over the first eight 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 13-26-year-old women were recruited for three cross-sectional studies from 2006-2014 (N=1180). Outcome variables were: 1) prevalence of ≥ 1 of 32 anogenital non-vaccine-type HPVs and 2) prevalence of ≥ 1 HPV type genetically related to HPV16 and HPV18. 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 2006-2014 there was no increase in non-vaccine-type HPV among vaccinated women (AOR 1.02, 95% 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 HPV16 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 HPV16. 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.

1 University of Cincinnati College of Medicine, Cincinnati, OH, 45229, US

2 McGill University, Montreal, QC, H4A 3T2, Canada

3 Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45229, US

4 Indiana University School of Medicine, Indianapolis, IN, 46202, US

Corresponding author: Jessica Kahn, MD MPH, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 4000, Cincinnati, OH 45229, Phone (513) 636-7764, Fax (513) 636-1129,

Potential conflicts of interest. Dr. Kahn has co-chaired two NIH-funded 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.

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

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