Human papillomavirus (HPV) DNA and p16 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 p16 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 p16 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 p16 Taishan Scholar Youth Project of Shandong Province, China.