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Open Access Highly Accessed Research article

A large, population-based study of age-related associations between vaginal pH and human papillomavirus infection

Megan A Clarke14*, Ana Cecilia Rodriguez2, Julia C Gage1, Rolando Herrero2, Allan Hildesheim1, Sholom Wacholder1, Robert Burk3 and Mark Schiffman1

Author Affiliations

1 Division of Cancer Epidemiology and Genetics, DHHS, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

2 Proyecto Epidemiológico Guanacaste, San José, Costa Rica

3 Department of Pediatrics, Microbiology & Immunology; Epidemiology & Population Health; and Obstetrics, Gynecology, and Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA

4 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute, 6120 Executive Blvd, EPS/7011, Rockville, MD 20852, USA

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BMC Infectious Diseases 2012, 12:33  doi:10.1186/1471-2334-12-33

Published: 8 February 2012



Vaginal pH is related to genital tract inflammation and changes in the bacterial flora, both suggested cofactors for persistence of human papillomavirus (HPV) infection. To evaluate the relationship between vaginal pH and HPV, we analyzed data from our large population-based study in Guanacaste, Costa Rica. We examined vaginal pH and the risk of HPV infection, cytological abnormalities, and C. trachomatis infection.


Our study included 9,165 women aged 18-97 at enrollment with a total of 28,915 visits (mean length of follow-up = 3.4 years). Generalized estimating equations were used to evaluate the relationship between vaginal pH and HPV infection (both overall and single versus multiple types) and low-grade squamous intraepithelial lesions (LSIL), the cytomorphic manifestation of HPV infection. The relationship between enrollment vaginal pH and C. trachomatis infection was assessed by logistic regression. Results were stratified by age at visit.


Detection of HPV was positively associated with vaginal pH, mainly in women < 35 years (p-trend = 0.009 and 0.007 for women aged < 25 and 25-34 years, respectively). Elevated vaginal pH was associated with 30% greater risk of infection with multiple HPV types and with LSIL, predominantly in women younger than 35 and 65+ years of age. Detection of C. trachomatis DNA was associated with increased vaginal pH in women < 25 years (OR 2.2 95% CI 1.0-5.0).


Our findings suggest a possible association of the cervical microenvironment as a modifier of HPV natural history in the development of cervical precancer and cancer. Future research should include studies of vaginal pH in a more complex assessment of hormonal changes and the cervicovaginal microbiome as they relate to the natural history of cervical neoplasia.

HPV; Vaginal pH; Cervical neoplasia; Aging; Chlamydia