Lynn Sadler

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

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. 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. 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. 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.

Patterns of recurrence and implications for follow-up in human papillomavirus-associated versus human papillomavirus-independent vulvar squamous cell carcinoma

To inform follow-up protocols, we investigated differences in incidence, number, and timing of recurrence by site between human papillomavirus (HPV)-Independent and HPV-associated vulvar squamous cell carcinoma. A retrospective clinicopathological single-institution cohort study was conducted of 471 patients with vulvar squamous cell carcinoma between 1990 and 2020. Tumors were classified as HPV-independent or HPV-associated, and the number, site, and time to recurrence were compared. Kaplan-Meier curves were developed for recurrence-free survival by stage, disease-specific survival by recurrence site, and cumulative incidence of recurrence for each tumor type. A total of 471 consecutive vulvar squamous cell carcinomas were identified during the study period; 251 HPV-independent and 208 HPV-associated, with 12 tumors unable to be classified. The median follow-up time was 41 months (range; 0-326). The median time to first recurrence was 22 months for HPV-independent and 43.5 months for HPV-associated (p = .014). In all-stage cancers, any type of recurrence occurred in 38.2% HPV-independent and 8.7% HPV-associated cases (p < .001). The cumulative recurrence rate (any site) for HPV-independent tumors at 5 years was 44% (95% confidence interval [CI] 37% to 52%) and 7% (95% CI 4% to 13%) for HPV-associated tumors. Local recurrence occurred in 29.5% of HPV-independent and 7.7% HPV-associated cases (p < .001), groin recurrence in 14.3% of HPV-independent and 1.4% of HPV-associated cases (p < .001), and distant recurrence in 8.4% of HPV-independent and 2.4% of HPV-associated cases (p = .006). HPV- independent tumors had a significantly higher number of multiple recurrences (18.7% vs 1.9%, p < .001). Following a first local recurrence, disease-specific survival was 86% (95% CI 33% to 98%) at both 3 and 5 years for HPV-associated tumors, compared with 61% (95% CI 47% to 73%) at 3 years and 48% (95% CI 33% to 62%) at 5 years for HPV-independent tumors. HPV-independent tumors have a 4.4-fold increased risk of any type of recurrence, with the first recurrence occurring 21 months earlier and with ongoing lifelong risk. Surveillance could be tailored by HPV status, extended for HPV-independent and reduced or patient-initiated for HPV-associated tumors.