Recurrent disease after treatment for cervical pre-cancer: determining whether prophylactic HPV vaccination could play a role in prevention of secondary lesions

Abstract

Existing modalities can effectively treat high-grade cervical intraepithelial neoplasia (CIN) but around 7% of treated women will develop recurrence of CIN grade 2 or above within 2 years of treatment. Post-treatment surveillance is therefore required to detect residual or recurrent disease. Since the implementation of human papillomavirus (HPV) vaccination programs in high-income countries, significant reductions in high-grade CIN have been recorded in vaccinated cohorts who were predominantly HPV-naïve at vaccination. There is still debate as to the extent of potential benefit from vaccination for women previously infected with HPV, given that HPV incidence in women falls with age and previously cleared infection provides at least some protection against reinfection. Whilst vaccination-induced antibodies could prevent type-specific new infections, it is unclear whether vaccination could also prevent reactivation of latent, previously acquired infection and subsequent disease. A review of the available evidence suggests a potential reduction in risk of recurrent disease if women diagnosed and treated for CIN are offered prophylactic vaccines. New modeled analyses and, ideally, a prospectively designed randomized controlled trial in women treated and then randomized to vaccination or placebo would provide much-needed additional evidence to support the effectiveness and cost-effectiveness of offering vaccination to women after treatment for CIN.

摘要

现有的治疗方法可以有效治疗高级别宫颈上皮内瘤变 (CIN), 但接受治疗的女性中大约7% 将在治疗后2年内发生CIN 2级或更高级别的复发。因此, 需要进行治疗后监测以发现残留或复发性疾病。自从高收入国家实施人乳头状瘤病毒(HPV) 疫苗接种计划以来, 在接种疫苗的人群中, 尤其是初次接种HPV疫苗的人群中, 高级别CIN的发病率显著减少。鉴于HPV在妇女中的发病率随着年龄的增长而下降, 而且以前已清除的感染至少提供了一些预防再感染的保护, 因此对于以前感染HPV的妇女接种疫苗的潜在益处的程度仍然存在争议。虽然疫苗诱导的抗体可以预防特定类型的新感染, 但目前尚不清楚接种疫苗是否也可以防止潜伏的、先前获得的感染和随后疾病的重新激活。对现有证据的回顾表明, 如果为被诊断为CIN并接受治疗的妇女提供预防性疫苗, 则可能降低复发疾病的风险。新的模型分析, 即理想情况下, 在接受治疗的妇女中随机分组予以接种疫苗或安慰剂的一项前瞻性、随机对照试验, 将提供急需的额外证据以支持为接受CIN治疗后的妇女提供疫苗接种的有效性和成本效益。

Keywords:

• Recurrence
• treatment
• vaccination
• cervical intraepithelial neoplasia
• excision

Potential conflict of interest

KC is co-principal investigator of an investigator-initiated trial of cytology and primary HPV screening in Australia (‘Compass’), which is conducted and funded by the VCS Foundation, a government-funded health-promotion charity. The VCS Foundation has received equipment and a funding contribution for the Compass trial from Roche Molecular Systems and Ventana USA. However, neither KC nor her institution on her behalf (Cancer Council NSW) has received direct or indirect funding from industry for Compass Australia or NZ or any other project. JMLB reports unrestricted investigator-initiated grants from MSD (papillomatosis typing study) and Seqirus (cervical cancer typing study) outside the submitted work; she has never received any personal financial benefits. KC and JMLB are investigators on the NHMRC-funded Centre for Research Excellence in Cervical Cancer Control. LSV has nothing to disclose.

Additional information

Funding

National Health and Medical Research Council (NHMRC) Australia, part-funded via the NHMRC Centre of Excellence for Cervical Cancer Control [C4; APP1135172].