Prior human papillomavirus-16/18 AS04-adjuvanted vaccination prevents recurrent high grade cervical intraepithelial neoplasia after definitive surgical therapy: Post-hoc analysis from a randomized controlled trial

Abstract

We evaluated the efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in preventing HPV-related disease after surgery for cervical lesions in a post-hoc analysis of the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681). Healthy women aged 15-25 years were randomized (1:1) to receive vaccine or control at months 0, 1 and 6 and followed for 4 years. Women were enrolled regardless of their baseline HPV DNA status, HPV-16/18 serostatus, or cytology, but excluded if they had previous or planned colposcopy. The primary and secondary endpoints of PATRICIA have been reported previously; the present post-hoc analysis evaluated efficacy in a subset of women who underwent an excisional procedure for cervical lesions after vaccination. The main outcome was the incidence of subsequent HPV-related cervical intraepithelial neoplasia grade 2 or greater (CIN2+) 60 days or more post-surgery. Other outcomes included the incidence of HPV-related CIN1+, and vulvar or vaginal intraepithelial neoplasia (VIN/VaIN) 60 days or more post-surgery. Of the total vaccinated cohort of 18,644 women (vaccine = 9,319; control = 9,325), 454 (vaccine = 190, control = 264) underwent an excisional procedure during the trial. Efficacy 60 days or more post-surgery for a first lesion, irrespective of HPV DNA results, was 88.2% (95% CI: 14.8, 99.7) against CIN2+ and 42.6% (-21.1, 74.1) against CIN1+. No VIN was reported and one woman in each group had VaIN2+ 60 days or more post-surgery. Women who undergo surgical therapy for cervical lesions after vaccination with the HPV-16/18 vaccine may continue to benefit from vaccination, with a reduced risk of developing subsequent CIN2+.

Keywords: cervical intraepithelial neoplasia; clinical trial; human papillomavirus vaccine; treatment.

Figure 1

Participant disposition. 1Number of subjects with at least one colposcopy referral during the study (total number of colposcopy procedures: n = 2,458 for vaccine; n = 2,723 for control). 2LEEP, cone, or knife. 3CIN2+ at least 60 days after first therapy. Abbreviations: CIN2+: cervical intraepithelial neoplasia grade 2 or greater; LEEP: loop electrosurgical excision procedure.

Figure 2

Biopsy type, histopathological diagnosis and oncogenic HPV DNA in lesion for women who had CIN2+ at least 60 days after surgical therapy for cervical disease. 1Case 1: no high‐risk HPV DNA detected in LEEP biopsy at month 20. Exit colposcopy at month 60 was normal. 2Case 5: cone treatment was not needed at month 49 and follow‐up cytology was normal. 3Case 6: subject was followed up according to local practice and colposcopy was done approximately 2 weeks later (outside of study). 4Case 7: colposcopy at months 30 and 48 were negative and no further treatment was done. 5Case 9: no further follow‐up information is available after month 49. Abbreviations: CIN: cervical intraepithelial neoplasia; f: disease‐free margins; c: compromised margins; Sq.met.: squamous metaplasia; VaIN: vaginal intraepithelial neoplasia; LEEP: loop electrosurgical excision procedure.