A large, population-based study of age-related associations between vaginal pH and human papillomavirus 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.The development of cervical cancer is linked to persistent infection with at least one of about a dozen carcinogenic genotypes of human papillomavirus (HPV)[1]. Most HPV infections are transient [2] and only a small minority of women with long-term, persistent infections are at an increased risk of progression to precancerous cervical lesions and cervical cancer [2,3]. Although this causal role is well established, relatively little is known about non-behavioral factors that influence risk of HPV acquisition and persistence. Alterations in the vaginal microenvironment, due to vaginal douching [4], bacterial vaginosis (BV) [5], and sexual