Risk of newly detected infections and cervical abnormalities in adult women seropositive or seronegative for naturally acquired HPV-16/18 antibodies.

BACKGROUND: Infections with human papillomavirus (HPV) types 16 and 18 account for ~70% of invasive cervical cancers but the degree of protection from naturally acquired anti-HPV antibodies is uncertain. We examined the risk of HPV infections as defined by HPV DNA detection and cervical abnormalities among women >25 years in the Human Papilloma VIrus Vaccine Immunogenicity ANd Efficacy trial's (VIVIANE, NCT00294047) control arm. METHODS: Serum anti-HPV-16/18 antibodies were determined at baseline and every 12 months in baseline DNA-negative women (N = 2687 for HPV-16 and 2705 for HPV-18) by enzyme-linked immunosorbent assay (ELISA) from blood samples. HPV infections were identified by polymerase chain reaction (PCR) every 6-months, and cervical abnormalities were confirmed by cytology every 12 months. Data were collected over a 7-year period. The association between the risk of type-specific infection and cervical abnormalities and serostatus was assessed using Cox proportional hazard models. RESULTS: Risk of newly detected HPV-16-associated 6-month persistent infections (PI) (hazard ratio [HR] = 0.56 [95%CI:0.32; 0.99]) and atypical squamous cells of undetermined significance (ASC-US+) (HR = 0.28 [0.12; 0.67]) were significantly lower in baseline seropositive vs baseline seronegative women. HPV-16-associated incident infections (HR = 0.81 [0.56; 1.16]) and 12-month PI (HR = 0.53 [0.24; 1.16]) showed the same trend. A similar trend of lower risk was observed in HPV-18-seropositive vs -seronegative women (HR = 0.95 [0.59; 1.51] for IIs, HR = 0.43 [0.16; 1.13] for 6-month PIs, HR = 0.31 [0.07; 1.36] for 12-month PIs, and HR = 0.61 [0.23; 1.61] for ASC-US+). CONCLUSIONS: Naturally acquired anti-HPV-16 antibodies were associated with a decreased risk of subsequent infection and cervical abnormalities in women >25 years. This possible protection was lower than that previously reported in 15- to 25-year-old women.

The natural history of cervical human papillomavirus infections and cervical cancer: gaps in knowledge and future horizons.

Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection. Most HPV infections are benign and resolve on their own, but some women develop persistent HPV infections. Persistent HPV infection with certain high-risk HPV genotypes is the necessary cause of most epithelial lesions of the uterine cervix. The importance of latent or quiescent HPV, waning immunity, hormonal milieu, microbiota, and other factors modifying the natural history of HPV infections across a woman's lifetime deserves further study. Promising biomarkers are emerging that may aid in defining which HPV-infected women are at risk of developing invasive cervical cancer.

Natural history of human papillomavirus infections, cytologic and histologic abnormalities, and cancer.

Over 100 human papillomavirus (HPV) types have been identified to date, of which over 40 infect the genital tract, primarily through sexual transmission. The many different genital HPV types appear to infect, resolve, or persist, and cause abnormal cytology and cervical intraepithelial neoplasia. Several cofactors have been associated with HPV persistence and lesion progression, including smoking, long-term oral contraceptive use, other sexually transmitted infections, host immunogenetics, and viral factors, such as HPV type and HPV variants. Given the discovery of HPV as the single primary cause of invasive cervical cancer, primary and secondary interventions have been realized, including HPV testing in cervical screening programs and prophylactic HPV vaccines. Because first generation HPV vaccines only target the two most common HPV types found in cervical cancer (HPV 16 and 18), cervical screening programs must continue, and the relative roles of HPV vaccination in young women and HPV testing in older women (alone or in conjunction with cytology) will be determined over the next decades.