背景:人乳头瘤病毒(HPV)DNA和p16INK4a阳性在外阴癌和外阴上皮内瘤变的发病机制中起着至关重要的作用。我们旨在研究全球外阴癌和外阴上皮内瘤变中HPVDNA和p16INK4a阳性的合并患病率。
方法:在本系统综述和荟萃分析中,我们搜索了PubMed,Embase,和Cochrane图书馆数据库在1986年1月1日至2022年5月6日之间发表的研究报告了HPVDNA的患病率,或p16INK4a阳性,或者两者兼而有之,组织学证实的外阴癌或外阴上皮内瘤变。包括至少5例病例的研究。研究水平的数据是从已发表的研究中提取的。随机效应模型用于检查外阴癌和外阴上皮内瘤变中HPVDNA和p16INK4a阳性的合并患病率。使用组织学亚型的分层分析进一步研究,地理区域,HPVDNA或p16INK4a检测方法,组织样本类型,HPV基因型,出版年份,和诊断时的年龄。此外,元回归用于探索异质性的来源。
结果:我们检索了6393个搜索结果,其中6233例因重复或应用我们的纳入和排除标准后被排除。我们还从参考文献列表的手动搜索中确定了两项研究。162项研究符合纳入系统评价和荟萃分析的条件。外阴癌中HPV的患病率(91项研究;n=8200)为39·1%(95%CI35·3-42·9),外阴上皮内瘤变(60项研究;n=3140)为76·1%(70·7-81·1)。外阴癌中最主要的HPV基因型是HPV16(78·1%[95%CI73·5-82·3]),其次是HPV33(7·5%[4·9-10·7])。同样,HPV16(80·8%[95%CI75·9-85·2])和HPV33(6·3%[3·9-9·2])也是外阴上皮内瘤变中最主要的两种HPV基因型。不同地理区域外阴癌中类型特异性HPV基因型的分布不同,HPV16在地区之间变化,在大洋洲患病率较高(89·0%[95%CI67·6-99·5]),在南美洲患病率较低(54·3%[30·2-77·4])。p16INK4a在外阴癌患者中的阳性率为34·1%(95%CI30·9-37·4;52项研究;n=6352),外阴上皮内瘤变患者为65·7%(52·5-77·7;23项研究;n=896)。此外,在HPV阳性外阴癌患者中,p16INK4a阳性患病率为73·3%(95%CI64·7-81·2),与13·8%(10·0-18·1)的HPV阴性外阴癌相比。HPV和p16INK4a双阳性的患病率在外阴癌中为19·6%(95%CI16·3-23·0),在外阴上皮内瘤变中为44·2%(26·3-62·8)。大多数分析具有较大的异质性(I2>75%)。
结论:外阴癌和外阴上皮内瘤变中HPV16和HPV33的高患病率强调了九价HPV疫苗在预防外阴肿瘤中的重要性。此外,这项研究强调了HPVDNA和p16INK4a双阳性在外阴肿瘤中的潜在临床意义.
背景:山东省泰山学者青年项目,中国。
Human papillomavirus (HPV) DNA and p16INK4a positivity have crucial roles in the pathogenesis of vulvar cancer and vulvar intraepithelial neoplasia. We aimed to examine the pooled prevalence of HPV DNA and p16INK4a positivity in vulvar cancer and vulvar intraepithelial neoplasia worldwide.
In this systematic
review and meta-analysis, we searched PubMed, Embase, and the Cochrane Library databases for studies published between Jan 1, 1986, and May 6, 2022, that reported the prevalence of HPV DNA, or p16INK4a positivity, or both, in histologically verified vulvar cancer or vulvar intraepithelial neoplasia. Studies on a minimum of five cases were included. Study-level data were extracted from the published studies. Random effect models were used to examine the pooled prevalence of HPV DNA and p16INK4a positivity in both vulvar cancer and vulvar intraepithelial neoplasia, which were further investigated using stratified analyses by histological subtype, geographical region, HPV DNA or p16INK4a detection method, tissue sample type, HPV genotype, publication year, and age at diagnosis. Additionally, meta-regression was applied to explore sources of heterogeneity.
We retrieved 6393 search results, of which 6233 were excluded for being duplicates or after application of our inclusion and exclusion criteria. We also identified two studies from manual searches of references lists. 162 studies were eligible for inclusion in the systematic
review and meta-analysis. The prevalence of HPV in vulvar cancer (91 studies; n=8200) was 39·1% (95% CI 35·3-42·9) and in vulvar intraepithelial neoplasia (60 studies; n=3140) was 76·1% (70·7-81·1). The most predominant HPV genotype in vulvar cancer was HPV16 (78·1% [95% CI 73·5-82·3]), followed by HPV33 (7·5% [4·9-10·7]). Similarly, HPV16 (80·8% [95% CI 75·9-85·2]) and HPV33 (6·3% [3·9-9·2]) were also the most two predominant HPV genotypes in vulvar intraepithelial neoplasia. The distribution of type-specific HPV genotypes in vulvar cancer among geographical regions was different, with HPV16 varying between regions, showing a high prevalence in Oceania (89·0% [95% CI 67·6-99·5]) and a low prevalence in South America (54·3% [30·2-77·4]). The prevalence of p16INK4a positivity in patients with vulvar cancer was 34·1% (95% CI 30·9-37·4; 52 studies; n=6352), and it was 65·7% (52·5-77·7; 23 studies; n=896) in patients with vulvar intraepithelial neoplasia. Furthermore, among patients with HPV-positive vulvar cancer, p16INK4a positivity prevalence was 73·3% (95% CI 64·7-81·2), compared with 13·8% (10·0-18·1) in HPV-negative vulvar cancer. The prevalence of double positivity for HPV and p16INK4a was 19·6% (95% CI 16·3-23·0) in vulvar cancer and 44·2% (26·3-62·8) in vulvar intraepithelial neoplasia. Most analyses had large heterogeneity (I2>75%).
The high prevalence of HPV16 and HPV33 in vulvar cancer and vulvar intraepithelial neoplasia emphasised the importance of nine-valent HPV vaccination in preventing vulvar neoplasm. Additionally, this study highlighted the potential clinical significance of double positivity for HPV DNA and p16INK4a in vulvar neoplasm.
Taishan Scholar Youth Project of Shandong Province, China.