Impact of HPV-16/18 AS04-adjuvanted vaccine on preventing subsequent infection and disease after excision treatment: post-hoc analysis from a randomized controlled trial

Abstract

Background: It is widely acknowledged that HPV prophylactic vaccine could prevent new infections and their associated lesions among women who are predominantly HPV-naive at vaccination. Yet there still remains uncertainty about whether HPV vaccination could benefit to individuals who have undergone surgery for cervical disease.

Methods: This post-hoc analysis intends to focus on intent-to-treat participants who underwent excision treatment at baseline and the follow-up period in a phase II/III, double-blind, randomized trial ( ClinicalTrials.gov , number NCT00779766 ) conducted in Jiangsu province, China. We evaluate the impact of HPV vaccination on preventing women from subsequent infection and cervical lesions (LSIL+ and CIN2+) after excision treatment.

Results: One hundred sixty-eight (vaccine, n = 87; placebo, n = 81) performed excisional treatment in this clinical trial. We observed a significant effect of vaccination on acquiring 14 high-risk HPV (HR-HPV) infection after treatment (vaccine efficacy: 27.0%; 95% CI 4.9, 44.0%). The vaccine efficacy against new infections after treatment for 14 HR-HPV infection was estimated as 32.0% (95%CI 1.8, 52.8%), and was 41.2% (95%CI -162.7, 86.8%) for HPV16/18 infection. The accumulative clearance rates of the vaccine group and placebo group were 88.9 and 81.6% for HPV16/18 infection (P = 0.345), 63.4, 48.7% for 14 HR-HPV infection (P = 0.062), respectively. No significant difference was observed on the persistent rate of HPV16/18, 14 HR-HPV infection and occurrence rate of LSIL+ between the two groups.

Conclusions: No significant evidence from this study showed that HPV-16/18 AS04-adjuvanted vaccine could lead to viral faster clearance or have any effect on the rates of persistent infection among women who had excision treatment. However, the vaccine may still benefit post-treatment women with "primary prophylactic" effect. Further research is required in clarifying the effect of using the prophylactic HPV vaccine as therapeutic agents.

Trial registration: ClinicalTrials.gov identifier: NCT00779766 . Date and status of trial registration: October 24, 2008. Completed; Has Results.

Keywords: Cervical Cancer; Clinical trial; Excision treatment; Human papillomavirus; Vaccine.

Conflict of interest statement

The institutions of FHZ received grants from the GSK group of companies for the conduct of the clinical trial. The GSK group of companies had no role in the analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. The other authors declare that they have no competing interests.

Figures

Fig. 1

Participant disposition. Abbreviations: LEEP: loop electrosurgical excision procedure

Fig. 2

Impact of HPV-16/18 AS04-adjuvanted vaccine on accumulative clearance rate and persistent infection rate among the women after excision treatment

Fig. 3

Impact of HPV-16/18 AS04-adjuvanted vaccine on occurrence of low-grade squamous intraepithelial lesion or worse (LSIL+)

Fig. 4

Biopsy type, histopathological diagnosis and HPV DNA result in lesion for women who had undergone surgical therapy for cervical disease. Case 1: the subject was HPV-16, 52 DNA positive, with ASCUS predicted by cytology at gynecological examination at visit 1. Case 2: occurred in a woman who, at baseline (visit1), was HPV-16 DNA positive, with HSIL predicted by cytology. Case 3: the woman was HPV-16, 59 DNA positive, with LSIL predicted by cytology at visit 1.And the subject was high-risk HPV DNA negative at month 18. HPV-39 was detected at month 30. Case 4: the subject was HPV-16, 31, 33 DNA positive, with HSIL predicted by cytology at gynecological examination at month 6. Case 5: the subject was HPV-58 DNA positive, with LSIL predicted by cytology at gynecological examination at month 66. Abbreviations: CIN: cervical intraepithelial neoplasia; VAIN: vaginal intraepithelial neoplasia; LEEP: loop electrosurgical excision procedure