MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, 90 High Holborn, London, UK.
Sussex Cancer Centre, Royal Sussex County Hospital, Eastern Road, Brighton, UK.
Br J Cancer. 2019 Jan;120(2):256-268. doi: 10.1038/s41416-018-0273-9. Epub 2018 Nov 28.
High-risk human papilloma viruses (HPV) are a causative agent of anogenital and oropharyngeal cancers. Patients treated for a preinvasive or invasive HPV-associated cancer may be at increased risk of a second such malignancy.
We performed a systematic review and random effects meta-analysis to estimate the risk of HPV-associated cancer after prior diagnosis. Studies reporting second cancers at anogenital and oropharyngeal sites after prior diagnoses (preinvasive/invasive HPV-associated cancer) were identified. Studies reporting standardised incidence ratios (SIRs) were included in formal meta-analyses of second cancer risk. (PROSPERO ID: CRD42016046974).
Searches returned 5599 titles, including 60 unique, eligible studies. Thirty-two (98 comparisons) presented SIRs for second cervical, anal, vulvo-vaginal, penile, and/or oropharyngeal cancers, included in the meta-analyses. All studies (and 95/98 comparisons) reported increased cancers in the population with previous HPV-associated cancer when compared to controls. Pooled SIRs for second primary cancers ranged from 1.75 (95% CI 0.66-4.67) for cervical cancer after primary anal cancer, to 13.69 (95% CI 8.56-21.89) for anal cancer after primary vulvo-vaginal cancer.
We have quantified the increased risk of second HPV-associated cancer following diagnosis and treatment for initial cancer or preinvasive disease. This has important implications for follow-up, screening, and future therapeutic trials.
高危型人乳头瘤病毒（HPV）是肛门生殖器和口咽癌的致病因素。接受过 HPV 相关癌前或侵袭性癌症治疗的患者可能有更高的罹患第二种此类恶性肿瘤的风险。
我们进行了系统评价和随机效应荟萃分析，以评估先前诊断后 HPV 相关癌症的风险。我们确定了报告先前诊断（癌前/侵袭性 HPV 相关癌症）后肛门生殖器和口咽部位第二癌的研究。报告标准化发病比（SIR）的研究被纳入第二癌风险的正式荟萃分析。（PROSPERO 注册号：CRD42016046974）。
搜索结果返回了 5599 个标题，包括 60 个独特的合格研究。32 项（98 项比较）报告了第二例宫颈、肛门、外阴阴道、阴茎和/或口咽癌的 SIR，这些研究被纳入荟萃分析。与对照组相比，所有研究（和 98 项比较中的 95 项）均报告了先前 HPV 相关癌症患者的癌症发病率增加。第二原发癌的汇总 SIR 范围从原发性肛门癌后宫颈癌的 1.75（95%CI 0.66-4.67），到原发性外阴阴道癌后肛门癌的 13.69（95%CI 8.56-21.89）。
我们已经量化了在诊断和治疗初始癌症或癌前病变后，第二例 HPV 相关癌症的风险增加。这对随访、筛查和未来的治疗试验有重要意义。
