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Updated: Jul 19, 2026

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Published on: March 11, 2014
p16 overexpression identifies HPV-positive vulvar squamous cell carcinomas
Mónica Santos1, Stefania Landolfi, Anna Olivella
1Department of Pathology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Immunohistochemical detection of p16 is a reliable marker for human papillomavirus (HPV)-positive vulvar squamous cell carcinomas (VSCCs), improving classification accuracy. This study found significant overlap in traditional histologic criteria for differentiating HPV-associated VSCCs.
Area of Science:
- Gynecologic Pathology
- Oncology
- Molecular Diagnostics
Background:
- Vulvar squamous cell carcinomas (VSCCs) are classified based on human papillomavirus (HPV) association.
- Basaloid/warty VSCCs are HPV-associated, while differentiated keratinizing VSCCs are not.
- Immunohistochemistry for p16 and p53 is proposed for differentiating these subtypes.
Purpose of the Study:
- To evaluate the utility of p16 and p53 immunohistochemistry in classifying VSCCs.
- To compare immunohistochemical findings with HPV detection and histologic criteria.
- To describe the clinicopathologic features of HPV-positive and HPV-negative VSCCs.
Main Methods:
- Histologic evaluation of 92 VSCC cases.
- Immunohistochemical analysis for p16 and p53.
- HPV detection and typing using polymerase chain reaction (PCR).
Main Results:
- HPV was detected in 17.4% of cases, predominantly HPV16.
- Significant discrepancies were noted between histology and HPV status.
- p16 immunostaining demonstrated high sensitivity (100%) and specificity (98.7%) for HPV-associated VSCCs, outperforming histologic criteria and p53 staining.
- p16 was positive in HPV-positive tumors and negative in most HPV-negative tumors.
- p53 was positive in most HPV-negative tumors and negative in HPV-positive tumors.
- No significant differences in clinical outcomes (age, stage, recurrence) were observed between HPV-positive and negative groups.
Conclusions:
- Traditional morphologic criteria for differentiating HPV-positive and negative VSCCs show considerable overlap.
- p16 immunostaining is a highly reliable marker for identifying HPV-associated VSCCs, significantly enhancing diagnostic accuracy.
- p53 can serve as a marker for non-HPV-associated VSCCs.
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