HPV-associated and HPV-independent vulvar squamous cell carcinoma: is there an impact of resection margins on local recurrence?

Abstract

Objective: This study aimed to investigate the impact of resection margins on the first local recurrence of vulvar squamous cell carcinoma, stratified by human papillomavirus (HPV) status: HPV-associated (HPV-A) and HPV-independent (HPV-I). It also investigated the association between precursor lesions of vulvar squamous cell carcinoma at the resection margins and the risk of first local vulvar squamous cell carcinoma recurrence.

Methods: This was a retrospective single-center clinicopathological case note review of patients treated with primary surgery for vulvar squamous cell carcinoma between January 1990 and December 2020, with follow-up until February 2024. The impact of pathological margins on first local recurrence was assessed for HPV-A and HPV-I tumors separately in univariable and multi-variable survival analyses.

Results: A total of 360 vulvar squamous cell carcinoma cases were identified. Local recurrences were reported in 12 of 166 (7.2%) HPV-A and 53 of 194 (27.3%) HPV-I tumors (p < .001). Pathological margins <8 mm were significantly associated with increased local recurrence in HPV-I vulvar squamous cell carcinoma, with both univariable (HR 2.34, 95% CI 1.33-4.10, p = .003) and multi-variable analysis (adjusted HR 2.06, 95% CI 1.14 to 3.71, p = .0017) confirming this association. No significant association was observed in HPV-A vulvar squamous cell carcinoma (HR 0.70, 95% CI 0.22 to 2.24, p = .55). The number of HPV-A recurrences precluded multi-variable analysis. After stratifying by HPV sub-type, there was no association between precursors at the margins and local recurrence.

Conclusions: Local recurrences are more common in HPV-I than HPV-A vulvar squamous cell carcinoma. Surgical margins may not influence the risk of local recurrence in HPV-A vulvar squamous cell carcinoma. However, in HPV-I vulvar squamous cell carcinoma, narrow resection margins of <8 mm appear to increase the risk of local recurrence. Therefore, HPV status should be incorporated into management protocols to risk-stratify follow-up care.