Department of Internal Medicine, The University of Texas Health Science Center, University of Texas Medical School at Houston, Houston.
Department of Management Policy and Community Health, The University of Texas School of Public Health, Houston.
JAMA Dermatol. 2016 Dec 1;152(12):1354-1364. doi: 10.1001/jamadermatol.2015.4530.
Existing epidemiological evidence remains controversial regarding the association between β-genus human papillomavirus (β-HPV) and cutaneous squamous cell carcinoma (cSCC) in immunocompetent individuals.
We aimed to clarify this association and evaluate type-specific β-HPV involvement.
We performed a systematic literature search of MEDLINE and EMBASE for studies in humans through June 18, 2014, with no restriction on publication date or language. The following search terms were used: "human papillomavirus" and "cutaneous squamous cell carcinoma or skin squamous cell carcinoma or cSCC or nonmelanoma skin neoplasms."
Articles were independently assessed by 2 reviewers. We only included case-control or cohort studies, in immunocompetent individuals, that calculated the odds ratio (OR) for cSCC associated with overall and type-specific β-HPV.
We first assessed the heterogeneity among study-specific ORs using the Q statistic and I2 statistic. Then, we used the random-effects model to obtain the overall OR and its 95% CI for all studies as well as for each type of HPV. We also tested and corrected for publication bias by 3 funnel plot-based methods. The quality of each study was assessed with the Newcastle Ottawa Scale.
Pooled ORs and 95% CIs for overall β-HPV and HPV types 5, 8, 15, 17, 20, 24, 36, and 38 association with skin biopsy proven cSCC.
Seventy-nine articles were assessed for eligibility; 14 studies met inclusion criteria for the meta-analysis and included 3112 adult immunocompetent study participants with cSCC and 6020 controls. For all detection methods, the overall association between β-HPV and cSCC was significant with an adjusted pooled OR (95% CI) of 1.42 (1.18-1.72). As for the type-specific analysis, types 5, 8, 15, 17, 20, 24, 36, and 38 showed a significant association with adjusted pooled ORs (95% CIs) of 1.4 (1.18-1.66), 1.39 (1.16-1.66), 1.25 (1.04-1.50), 1.34 (1.19-1.52), 1.38 (1.21-1.59), 1.26 (1.09-1.44), 1.23 (1.01-1.50), and 1.37 (1.13-1.67) respectively. Our subgroup analysis in studies using only serology for HPV detection showed a significant association between overall β-HPV and HPV subtypes 5, 8, 17, 20, 24, and 38 with an increased risk of cSCC development.
This study serves as added evidence supporting β-HPV as a risk factor for cSCC in healthy individuals. The subgroup analysis highlights this significant association for HPV 5, 8, 17, 20, and 38, which may help to direct future prevention efforts.
重要性：现有的流行病学证据仍然存在争议，即β 型人乳头瘤病毒（β-HPV）与免疫功能正常个体的皮肤鳞状细胞癌（cSCC）之间的关联。
目的：我们旨在阐明这种关联，并评估特定类型的 β-HPV 参与情况。
数据来源：我们对 MEDLINE 和 EMBASE 进行了系统的文献检索，检索了截至 2014 年 6 月 18 日的人类研究，没有对发表日期或语言进行限制。使用了以下搜索词：“人乳头瘤病毒”和“皮肤鳞状细胞癌或皮肤鳞状细胞癌或 cSCC 或非黑色素瘤皮肤肿瘤”。
研究选择：由两名独立的审查员评估文章。我们仅纳入了在免疫功能正常个体中进行的病例对照或队列研究，这些研究计算了与总体和特定类型的 β-HPV 相关的 cSCC 的比值比（OR）。
数据提取和综合：我们首先使用 Q 统计量和 I2 统计量评估了研究特异性 OR 之间的异质性。然后，我们使用随机效应模型获得了所有研究以及每种 HPV 的总体 OR 及其 95%置信区间。我们还使用了 3 种基于漏斗图的方法来检验和校正发表偏倚。使用纽卡斯尔-渥太华量表评估了每项研究的质量。
主要结果和测量：总体 β-HPV 和 HPV 类型 5、8、15、17、20、24、36 和 38 与皮肤活检证实的 cSCC 相关的汇总 OR 和 95%CI。
结果：评估了 79 篇文章的合格性；14 项研究符合荟萃分析的纳入标准，包括 3112 名患有 cSCC 的成年免疫功能正常的研究参与者和 6020 名对照者。对于所有检测方法，β-HPV 与 cSCC 之间的总体关联具有统计学意义，调整后的合并 OR（95%CI）为 1.42（1.18-1.72）。对于特定类型的分析，类型 5、8、15、17、20、24、36 和 38 与调整后的合并 OR（95%CI）分别为 1.4（1.18-1.66）、1.39（1.16-1.66）、1.25（1.04-1.50）、1.34（1.19-1.52）、1.38（1.21-1.59）、1.26（1.09-1.44）、1.23（1.01-1.50）和 1.37（1.13-1.67）具有统计学意义。我们在仅使用血清学方法检测 HPV 的研究中的亚组分析表明，总体 β-HPV 与 HPV 亚型 5、8、17、20、24 和 38 之间存在显著关联，与 cSCC 发病风险增加相关。
结论和相关性：本研究为支持β-HPV 是健康个体中 cSCC 的风险因素提供了额外的证据。亚组分析突出了 HPV 5、8、17、20 和 38 之间的这种显著关联，这可能有助于指导未来的预防工作。
