A 2-year prospective study of human papillomavirus persistence among women with a cytological diagnosis of atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion

Background. Cervical cancer is caused by persistent infection with human papillomavirus (HPV). Most infections and associated lesions clear spontaneously. It is important to define the determinants and timing of clearance, so that viral persistence can be recognized and managed. Methods. We investigated HPV natural history among 4504 subjects from ALTS (Atypical Squamous Cells of Undetermined Significance/ Low- Grade Squamous Intraepithelial Lesions Triage Study). A discrete- time Markov model was used to simultaneously describe the prevalence, incidence, and persistence of type- specific HPV infection over 24 months in women with equivocal or mildly abnormal cytological results. Interactions between multiple HPV types infecting the same woman were examined for incidence of new infection (after an HPV- 16 infection) and persistence of a current infection within groups defined by phylogenetic relatedness or by carcinogenicity. Results. Ninety-one percent (95% credible interval [CI], 90% - 92%) of prevalent HPV infections at enrollment cleared within 24 months. The probability that an infection would persist for a further 6 months increased with the duration of infection, from 37% (95% CI, 35% - 39%) for a newly observed infection to 65% (95% CI, 61% 70%) for an infection that had already persisted for similar to 18 months. No consistent evidence of interactions was found between multiple HPV types regarding the incidence of new infection after an HPV- 16 infection or regarding persistence of current HPV infection. Conclusion. Although virtually all HPV infections clear within 2 years, the remaining infections have a high potential for persistence and, by implication, progression to precancer and cancer. Once biological and behavioral determinants are controlled for, HPV infections with different types seem to be independent of each other.