title: p16 overexpression identifies HPV-positive vulvar squamous cell carcinomas.
abstract: Two types of vulvar squamous cell carcinomas (VSCCs) are recognized according to their relationship to human papillomavirus (HPV). Basaloid or warty carcinomas are considered HPV-associated tumors, whereas differentiated keratinizing neoplasms are considered non-HPV-associated. Recently, immunohistochemical detection of p16 and p53 has been proposed to differentiate these 2 types of VSCCs. We conducted a histologic study with immunohistochemical evaluation of p16 and p53 and HPV detection and typing by polymerase chain reaction using 2 different sets of primers in 92 cases of VSCCs to evaluate the usefulness of immunohistochemistry in the classification of VSCCs and to describe the clinico-pathologic characteristics of both types of VSCCs. HPV was detected in 16/92 (17.4%) specimens, HPV16 being identified in 75% of positive cases. A significant number of discrepancies between histology and HPV detection were observed, with 37.5% of HPV-positive tumors being keratinizing and 9.2% of HPV-negative carcinomas showing basaloid or warty features. Diffuse positivity for p16 and p53 was observed in 100% and 6.2% of HPV-positive tumors and in 2.3% and 64.5% of HPV-negative neoplasms, respectively. The sensitivity and specificity of p16 immunostaining to detect HPV-associated carcinomas (100% and 98.7%, respectively) were better than those of histologic criteria (93.8% and 35.5%) and of p53 negative stain (62.5% and 93.4%). Vulvar intraepithelial neoplasia grade 3 of basaloid/warty type was identified in 53.8% HPV-positive tumors, including 3 keratinizing tumors. All these cases were p16 positive and p53 negative. Vulvar intraepithelial neoplasia grade 3 of differentiated type was observed in 45.6% of HPV-negative cases; 90.8% of them were positive for p53 but all were negative for p16. No differences in age, stage, or development of recurrence were observed between HPV-positive and negative tumors. In summary, the current morphologic criteria to discriminate HPV-positive and negative VSCCs have a significant overlap. Immunostaining for p16 is a reliable marker for HPV-positive VSSCs, which improves the results of histologic classification.
authors.affiliation: Department of Pathology, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Santos
authors.forename: Stefania
authors.initials: S
authors.lastname: Landolfi
authors.forename: Anna
authors.initials: A
authors.lastname: Olivella
authors.forename: Belen
authors.initials: B
authors.lastname: Lloveras
authors.forename: Joellen
authors.initials: J
authors.lastname: Klaustermeier
authors.forename: Helena
authors.initials: H
authors.lastname: Suárez
authors.forename: Llúcia
authors.initials: L
authors.lastname: Alòs
authors.forename: Lluís M
authors.initials: LM
authors.lastname: Puig-Tintoré
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Jaume
authors.initials: J
authors.lastname: Ordi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000145:classification / Q000378:metabolism / Q000821:virology*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D030361:Papillomavirus Infections / Q000150:complications* / Q000378:metabolism; D011230:Precancerous Conditions / Q000821:virology; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014412:Tumor Virus Infections / Q000150:complications / Q000378:metabolism; D014846:Vulvar Neoplasms / Q000145:classification / Q000378:metabolism / Q000821:virology*
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D016159:Tumor Suppressor Protein p53