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Prevalence of HPV DNA and p16INK4a Positivity in Vulvar Cancer and Vulvar Intraepithelial Neoplasia


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In a global systematic review and meta-analysis reported in The Lancet Oncology, Li et al found a high prevalence of human papillomavirus (HPV) genotype 16 and HPV33 in vulvar cancer and vulvar intraepithelial neoplasia, as well as a high frequency of p16INK4a positivity in HPV-positive vulvar cancer.

Study Details

The study included a literature search for studies published between January 1986 and May 2022 that reported the prevalence of HPV DNA, p16INK4a positivity, or both in histologically verified vulvar cancer or vulvar intraepithelial neoplasia. A total of 162 studies were eligible for inclusion in the systematic review and meta-analysis.

Key Points

The prevalence of HPV in vulvar cancer (91 studies; n = 8,200) was 39.1% (95% confidence interval [CI] = 35.3%–42.9%) and the prevalence in vulvar intraepithelial neoplasia (60 studies; n = 3,140) was 76.1% (95% CI = 70.7%–81.1%). The most common HPV genotypes in vulvar cancer were HPV16 (78.1%, 95% CI = 73.5%–82.3%) and HPV33 (7.5%, 95% CI = 4.9%–10.7%). HPV16 (80.8%, 95% CI = 75.9%–85.2%) and HPV33 (6.3%, 95% CI = 3.9%–9.2%) were also the most common genotypes in vulvar intraepithelial neoplasia.

The distribution of HPV genotypes in vulvar cancer differed among geographic regions. For example, the prevalence of HPV16 varied between 89.0% (95% CI = 67.6%–99.5%) in Oceania and 54.3% (95% CI = 30.2%–77.4%) in South America.

The prevalence of p16INK4a positivity in vulvar cancer (52 studies; n = 6,352) was 34.1% (95% CI = 30.9%–37.4%), and the prevalence in vulvar intraepithelial neoplasia (23 studies; n = 896) was 65.7% (95% CI = 52.5%–77.7%). Among patients with HPV-positive vulvar cancer, p16INK4a positivity prevalence was 73.3% (95% CI = 64.7%–81.2%), compared with 13.8% (95% CI = 10.0%–18.1%) in HPV-negative vulvar cancer. The overall prevalence of double positivity for HPV and p16INK4a was 19.6% (95% CI = 16.3%–23.0%) in vulvar cancer and 44.2% (95% CI = 26.3%–62.8%) in vulvar intraepithelial neoplasia.

The investigators concluded, “The high prevalence of HPV16 and HPV33 in vulvar cancer and vulvar intraepithelial neoplasia emphasized 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.”

Kun Song, PhD, of the Department of Obstetrics and Gynaecology, Qilu Hospital of Shandong University, Shandong, China, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the Taishan Scholar Youth Project of Shandong Province. For full disclosures of the study authors, visit thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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