HPV DNA In-Situ Hybridization, p16 and p53 in a Cohort of 128 Vulvar Squamous Cell Carcinomas.
Ghassan Allo, Anna Marie Mulligan, Danny Ghazarian, Ming Tsao, Helen Mackay, Blaise A Clarke. University of Toronto, ON, Canada; University Health Network, Toronto, ON, Canada; St. Micheal's Hospital, Toronto, ON, Canada
Background: Vulvar squamous cell carcinomas may develop via two different pathways: the most common pathway is HPV negative well differentiated keratinizing squamous cell carcinoma arising in elderly women, often in a background of lichen sclerosis and differentiated vulvar intraepithelial neoplasia; HPV positive vulvar squamous cell carcinoma occurs in younger women in association with usual vulvar intraepithelial neoplasia. P53 is typically over-expressed in the former and p16 in the latter. We analyzed p16, p53 and HPV integration in a cohort of 128 cases of squamous cell carcinoma of the vulva and determined the prognostic significance of these biomarkers.
Design: An annotated, duplicate core tissue microarray of 128 cases of vulvar squamous cell carcinoma was constructed. HPV DNA in situ hybridization and p16 and p53 immunohistochemical staining were performed. Statistical analysis was performed using JMP v8.0.2 (SAS institute, Carey, NC USA).
Results: HPV and p16 positivity were highly correlated. Thirteen percent of cases were HPV positive. Of these, 87% were positive for p16 and 7% for p53. Twenty five per cent of cases were p16 positive, of which 45% were HPV positive and 18% were p53 positive. Forty-eight per cent of cases were p53 positive and of these only 1.8% were HPV positive and 10.7% p16 positive. HPV was significantly more likely to be positive in p16 positive cancers than p53 positive cancers (P<0.001). P53 was more likely to be positive in HPV negative cases compared to HPV positive cases (P=0.006). There was no significant difference in median age between the HPV positive and negative groups. There was no significant difference in 5 Year disease specific survival and relapse free survival based on HPV status, p16 and p53 staining.
Conclusions: This data supports a dual pathway of vulvar squamous cell carcinoma progression. Unlike previous studies on vulva cancer and head and neck squamous cancer we did not demonstrate biomarker dependent outcome differences. Correlation with HPV PCR, full section staining and morphology is being performed.
Category: Gynecologic & Obstetrics
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 129, Wednesday Morning