Unit of Virus, Lifestyle, and Genes, Danish Cancer Society Research Centre, Copenhagen, Denmark.
Unit of Statistics and Pharmacoepidemiology, Danish Cancer Society Research Centre, Copenhagen, Denmark.
Lancet Oncol. 2019 Jan;20(1):145-158. doi: 10.1016/S1470-2045(18)30682-X. Epub 2018 Dec 17.
Although previous meta-analyses have examined human papillomavirus (HPV) DNA prevalence in penile cancer, none, to our knowledge, have assessed pooled HPV DNA prevalence in penile intraepithelial neoplasia or p16 percent positivity in penile cancer and penile intraepithelial neoplasia. Therefore, we aimed to examine the prevalence of HPV DNA and p16 positivity in penile cancer and penile intraepithelial neoplasia worldwide.
In this systematic review and meta-analysis, we searched PubMed, Embase, and the Cochrane Library until July 24, 2017, for English-language articles published from Jan 1, 1986, onwards reporting the prevalence of HPV DNA and p16 positivity, either alone or in combination, in at least five cases of penile cancer or penile intraepithelial neoplasia. Only studies that used PCR or hybrid capture for the detection of HPV DNA and immunohistochemical staining or methylation for the detection of p16 were included. Data were extracted and subsequently crosschecked, and inconsistencies were discussed to reach consensus. Using random-effects models, we estimated the pooled prevalence and 95% CI of HPV DNA and p16 positivity in penile cancer and penile intraepithelial neoplasia, stratifying by histological subtype and HPV DNA or p16 detection method. Type-specific prevalence of HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, and HPV45 in penile cancer was estimated.
Our searches identified 1836 non-duplicate records, of which 73 relevant papers (71 studies) were found to be eligible. The pooled HPV DNA prevalence in penile cancer (52 studies; n=4199) was 50·8% (95% CI 44·8-56·7; I=92·6%, p<0·0001). A high pooled HPV DNA prevalence was seen in basaloid squamous cell carcinomas (84·0%, 95% CI 71·0-93·6; I=48·0%, p=0·0197) and in warty-basaloid carcinoma (75·7%, 70·1-81·0; I=0%, p=0·52). The predominant oncogenic HPV type in penile cancer was HPV16 (68·3%, 95% CI 58·9-77·1), followed by HPV6 (8·1%, 4·0-13·7) and HPV18 (6·9%, 2·9-12·4). The pooled HPV DNA prevalence in penile intraepithelial neoplasia (19 studies; n=445) was 79·8% (95% CI 69·3-88·6; I=83·2%, p<0·0001). The pooled p16 percent positivity in penile cancer (24 studies; n=2295) was 41·6% (95% CI 36·2-47·0; I=80·6%, p<0·0001), with a high pooled p16 percent positivity in HPV-related squamous cell carcinoma (85·8%, 95% CI 72·1-95·4; I=56·4%, p=0·0011) as compared with non-HPV-related squamous cell carcinoma (17·1%, 7·9-29·1; I=78·3%, p<0·0001). Moreover, among HPV-positive cases of penile cancer, the p16 percent positivity was 79·6% (95% CI 65·7-90·7; I=89·9%, p<0·0001), compared with 18·5% (9·6-29·6; I=89·3%, p<0·0001) in HPV-negative penile cancers. The pooled p16 percent positivity in penile intraepithelial neoplasia (six studies; n=167) was 49·5% (95% CI 18·6-80·7).
A large proportion of penile cancers and penile intraepithelial neoplasias are associated with infection with HPV DNA (predominantly HPV16), emphasising the possible benefits of HPV vaccination in men and boys.
None.
虽然之前的荟萃分析已经研究了人乳头瘤病毒（HPV）在阴茎癌中的 DNA 流行率，但据我们所知，没有一项分析评估了阴茎上皮内瘤变中 HPV DNA 的总体流行率或阴茎癌和阴茎上皮内瘤变中 p16 的阳性百分比。因此，我们旨在评估全球范围内阴茎癌和阴茎上皮内瘤变中 HPV DNA 和 p16 阳性的流行率。
在这项系统评价和荟萃分析中，我们检索了 PubMed、Embase 和 Cochrane 图书馆，截至 2017 年 7 月 24 日，查找了自 1986 年 1 月 1 日起发表的英语文章，这些文章报告了至少 5 例阴茎癌或阴茎上皮内瘤变中 HPV DNA 和 p16 阳性的流行率，无论是单独报告还是联合报告。仅包括使用聚合酶链反应或杂交捕获检测 HPV DNA 和免疫组化染色或甲基化检测 p16 的研究。提取数据，然后交叉核对，不一致的地方进行讨论以达成共识。使用随机效应模型，我们根据组织学亚型和 HPV DNA 或 p16 检测方法，估计了阴茎癌和阴茎上皮内瘤变中 HPV DNA 和 p16 阳性的汇总流行率和 95%置信区间。估计了 HPV6、HPV11、HPV16、HPV18、HPV31、HPV33 和 HPV45 在阴茎癌中的型特异性流行率。
我们的搜索共确定了 1836 条非重复记录，其中发现 73 篇相关论文（71 项研究）符合纳入标准。52 项研究（n=4199）的汇总 HPV DNA 流行率在阴茎癌中为 50.8%（95%CI 44.8-56.7；I=92.6%，p<0.0001）。基底样鳞状细胞癌（84.0%，95%CI 71.0-93.6；I=48.0%，p=0.0197）和疣状基底细胞癌（75.7%，95%CI 70.1-81.0；I=0%，p=0.52）中 HPV DNA 的高流行率。阴茎癌中的主要致癌 HPV 型是 HPV16（68.3%，95%CI 58.9-77.1），其次是 HPV6（8.1%，4.0-13.7）和 HPV18（6.9%，2.9-12.4）。19 项研究（n=445）的汇总 HPV DNA 流行率在阴茎上皮内瘤变中为 79.8%（95%CI 69.3-88.6；I=83.2%，p<0.0001）。24 项研究（n=2295）的汇总 p16 阳性百分比在阴茎癌中为 41.6%（95%CI 36.2-47.0；I=80.6%，p<0.0001），其中 HPV 相关鳞状细胞癌（85.8%，95%CI 72.1-95.4；I=56.4%，p=0.0011）的 p16 阳性百分比明显高于非 HPV 相关鳞状细胞癌（17.1%，7.9-29.1；I=78.3%，p<0.0001）。此外，在 HPV 阳性的阴茎癌病例中，p16 阳性百分比为 79.6%（95%CI 65.7-90.7；I=89.9%，p<0.0001），而 HPV 阴性的阴茎癌中为 18.5%（9.6-29.6；I=89.3%，p<0.0001）。在 6 项研究（n=167）中，阴茎上皮内瘤变的汇总 p16 阳性百分比为 49.5%（95%CI 18.6-80.7）。
很大一部分阴茎癌和阴茎上皮内瘤变与 HPV DNA 感染有关（主要是 HPV16），这强调了 HPV 疫苗在男性和男孩中的潜在益处。
无。
