Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment

Abstract

BACKGROUNDHuman papillomavirus (HPV) vaccines prevent HPV infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an HPV-associated lesion is not fully understood.OBJECTIVESTo determine whether HPV-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions.STUDY DESIGNWe included 1711 women (18–25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted HPV-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2+. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated.RESULTSMedian follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human papillomavirus types present at enrollment. Vaccine efficacy for human papillomavirus 16/18 clearance and against human papillomavirus 16/18 progression from infection to cervical intraepithelial neoplasia 2+ were −5.4% (95% confidence interval −19,10) and 0.3% (95% confidence interval −69,41), respectively. Among treated women, 34.1% had oncogenic infection and 1.6% had cervical intraepithelial neoplasia 2+ detected after treatment, respectively, and of these 69.8% and 20.0% were the result of new infections. We observed no significant effect of vaccination on rates of infection/lesions after treatment. Vaccine efficacy estimates for human papillomavirus 16/18 associated persistent infection and cervical intraepithelial neoplasia 2+ after treatment were 34.7% (95% confidence interval −131, 82) and −211% (95% confidence interval −2901, 68), respectively. We observed evidence for a partial and nonsignificant protective effect of vaccination against new infections absent before treatment. For incident human papillomavirus 16/18, human papillomavirus 31/33/45, and oncogenic human papillomavirus infecti...

In RRP, serologic response to HPV is frequently absent and slow to develop

“…While the HPV vaccine efficacy in ano-genital HPV prevention is well established, its utility in treatment is viewed by many with skepticism. The cell biology of how neutralizing antibodies prevent infection [27] has been established but it does not include a pathway that would predict eradication of established infection, particularly high-risk HPV, and clinical studies in cervical infection [28,29] and genital warts [30] confirm as much. For several decades, Bonagura et al have investigated the cellular humoral response in RRP [31].…”

The Use of Both Therapeutic and Prophylactic Vaccines in the Therapy of Papillomavirus Disease

“…For these HPV16/18 infections, in the cohort of women with HPV infection but without precancer, the efficacy of clearance was 5.4%, with progression to CIN1 seen for 15.5%, and to CIN2, for 0.3%. Moreover, after the loop electrosurgical excision, the vaccination had no significant effects on HPV16/18 infections and/or HPV16/18-associated cytological and histological lesions (127).…”

Trends in cervical cancer incidence in younger US women from 2000 to 2013

“…[20] Studies have found that the vaccine strongly protects against HPV acquisition,[21,22] but does not impact HPV clearance or disease regression;[23] and that most ICCs do not develop for at least one decade after HPV acquisition. [24,25] The vaccine was approved in 2006, seven years prior to our end of follow-up.…”