Vulvar squamous cell carcinoma arising on Human Papillomavirus-independent Precursors Mimicking High-grade Squamous Intraepithelial Lesion: a distinct and highly recurrent subtype of vulvar cancer.

Abstract

Each category of vulvar squamous cell carcinoma (VSCC), human papillomavirus (HPV)-associated and HPV-independent, arises on a specific intraepithelial precursor: high-grade squamous intraepithelial lesions (HSIL) and differentiated vulvar intraepithelial neoplasia (dVIN), respectively. However, a subset of HPV-independent VSCC arises on an intraepithelial precursor closely mimicking HSIL. We aimed to explore the clinic-pathological features of the HPV-independent tumors with HSIL-like lesions and compare them with HPV-independent VSCC with dVIN and HPV-associated tumors with HSIL. We retrospectively identified 105 cases of surgically treated VSCC with adjacent intraepithelial precursors. The cases were classified into three groups based on the HPV status and the adjacent precursor identified: 1) HPV-associated VSCC with HSIL (n=26), 2) HPV-independent VSCC with dVIN lesions (n=54), and 3) HPV-independent VSCC with HSIL-like lesions (n=25). We analyzed the histological and clinical features including the recurrence-free survival and disease-specific survival in the three groups. Patients with HPV-independent VSCC with HSIL-like lesions and with dVIN were older than patients with HPV-associated VSCC (76 and 77 years, vs. 66, respectively, p<0.001). HPV-independent VSCC with HSIL-like lesions recurred more frequently (hazard ratio (HR)=3.87; p<0.001) than HPV-independent VSCC with dVIN (HR=2.27; p=0.1) and HPV-associated VSCC (HR=1). In the multivariate analysis HPV-independent VSCC with HSIL-like lesions remained significant for recurrence. No differences in disease-specific survival were observed between the three groups. Even though VSCC with HSIL-like lesions are not associated with higher mortality, they are more likely to recur and might benefit from more intensive treatment strategies and closer surveillance after treatment.