Department of Otolaryngology-Head and Neck Surgery, UT Southwestern Medical Center, Dallas, Texas.
Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas.
Cancer. 2021 Mar 15;127(6):850-864. doi: 10.1002/cncr.33221. Epub 2020 Dec 3.
Despite the significant societal burden of human papillomavirus (HPV)-associated cancers, clinical screening interventions for HPV-associated noncervical cancers are not available. Blood-based biomarkers may help close this gap in care.
Five databases were searched, 5687 articles were identified, and 3631 unique candidate titles and abstracts were independently reviewed by 2 authors; 702 articles underwent a full-text review. Eligibility criteria included the assessment of a blood-based biomarker within a cohort or case-control study.
One hundred thirty-seven studies were included. Among all biomarkers assessed, HPV-16 E seropositivity and circulating HPV DNA were most significantly correlated with HPV-associated cancers in comparison with cancer-free controls. In most scenarios, HPV-16 E6 seropositivity varied nonsignificantly according to tumor type, specimen collection timing, and anatomic site (crude odds ratio [cOR] for p16+ or HPV+ oropharyngeal cancer [OPC], 133.10; 95% confidence interval [CI], 59.40-298.21; cOR for HPV-unspecified OPC, 25.41; 95% CI, 8.71-74.06; cOR for prediagnostic HPV-unspecified OPC, 59.00; 95% CI, 15.39-226.25; cOR for HPV-unspecified cervical cancer, 12.05; 95% CI, 3.23-44.97; cOR for HPV-unspecified anal cancer, 73.60; 95% CI, 19.68-275.33; cOR for HPV-unspecified penile cancer, 16.25; 95% CI, 2.83-93.48). Circulating HPV-16 DNA was a valid biomarker for cervical cancer (cOR, 15.72; 95% CI, 3.41-72.57). In 3 cervical cancer case-control studies, cases exhibited unique microRNA expression profiles in comparison with controls. Other assessed biomarker candidates were not valid.
HPV-16 E6 antibodies and circulating HPV-16 DNA are the most robustly analyzed and most promising blood-based biomarkers for HPV-associated cancers to date. Comparative validity analyses are warranted. Variations in tumor type-specific, high-risk HPV DNA prevalence according to anatomic site and world region highlight the need for biomarkers targeting more high-risk HPV types. Further investigation of blood-based microRNA expression profiling appears indicated.
尽管人乳头瘤病毒（HPV）相关癌症给社会带来了巨大负担，但目前尚无针对 HPV 相关非宫颈癌的临床筛查干预措施。基于血液的生物标志物可能有助于填补这一护理空白。
我们检索了 5 个数据库，确定了 5687 篇文章，并由 2 位作者独立对 3631 篇独特的候选标题和摘要进行了回顾；702 篇文章进行了全文审查。纳入标准包括在队列或病例对照研究中评估基于血液的生物标志物。
共纳入 137 项研究。在所有评估的生物标志物中，HPV-16 E 血清阳性和循环 HPV DNA 与 HPV 相关癌症的相关性最显著，与无癌对照组相比。在大多数情况下，HPV-16 E6 血清阳性与肿瘤类型、标本采集时间和解剖部位无关（p16+或 HPV+口咽癌[OPC]的粗比值比[cOR]为 133.10；95%置信区间[CI]为 59.40-298.21；HPV 未特指 OPC 的 cOR 为 25.41；95%CI 为 8.71-74.06；HPV 未特指 OPC 的预诊断 cOR 为 59.00；95%CI 为 15.39-226.25；HPV 未特指宫颈癌的 cOR 为 12.05；95%CI 为 3.23-44.97；HPV 未特指肛门癌的 cOR 为 73.60；95%CI 为 19.68-275.33；HPV 未特指阴茎癌的 cOR 为 16.25；95%CI 为 2.83-93.48）。循环 HPV-16 DNA 是宫颈癌的有效生物标志物（cOR，15.72；95%CI，3.41-72.57）。在 3 项宫颈癌病例对照研究中，与对照组相比，病例表现出独特的 microRNA 表达谱。其他评估的候选生物标志物无效。
到目前为止，HPV-16 E6 抗体和循环 HPV-16 DNA 是分析最充分、最有前途的 HPV 相关癌症的基于血液的生物标志物。有必要进行比较有效性分析。根据解剖部位和世界区域，肿瘤类型特异性、高危 HPV DNA 流行率的差异突出表明需要针对更多高危 HPV 类型的生物标志物。进一步研究基于血液的 microRNA 表达谱似乎是必要的。
