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Introduction: Vulvar squamous cell carcinoma develops through two separate pathways, associated with the presence or absence of high-risk human papilloma virus (HPV). The objective of this study was to evaluate treatment response and clinical outcomes in women with HPV-associated versus HPV-independent vulvar squamous cell carcinoma treated with primary radiation therapy, in order to determine the ability to use HPV status as a predictor of response to radiation therapy., Methods: This was a retrospective cohort study combining data from British Columbia Cancer, Canada and Duke University, USA. Patients were included who had been treated with radiation therapy but excluded if they had received major surgical interventions. Immunohistochemistry for p16 (as a surrogate for high-risk HPV infection) and p53 was performed. We analyzed the univariable association between p16 status and clinico-pathological features and performed univariable survival analysis for p16., Results: Forty-eight patients with vulvar squamous cell carcinoma treated with primary radiation therapy were identified: 26 p16 positive/HPV-associated patients and 22 p16 negative/HPV-independent patients. p16 positive vulvar squamous cell carcinoma demonstrated a significantly improved overall survival (HR 0.39, p=0.03) and progression-free survival (HR 0.35, p=0.02). In women treated with definitive radiation therapy, p16 positivity was associated with improved overall survival (HR 0.29, p<0.01) and progression-free survival (HR 0.21, p<0.01). Among patients who received sensitizing chemotherapy, a significant association was observed with p16 positive tumors and overall survival (HR 0.25, p=0.03) and progression-free survival (HR 0.09, p<0.01)., Conclusion: This study suggests that HPV status in vulvar squamous cell carcinoma has both prognostic and predictive implications, with increased radiosensitivity demonstrated in HPV-associated vulvar squamous cell carcinoma. Implications may include radiation dose de-escalation for HPV-associated vulvar squamous cell carcinoma and increased surgical aggressiveness for HPV-independent vulvar squamous cell carcinoma., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The objective of this study was to evaluate patterns of care and the survival impact of primary radiation and preoperative radiation therapy with surgery in women with locally advanced vulvar cancer using a large national cohort., Methods and Materials: Women with vulvar cancer, diagnosed from 2004 to 2012, who received primary or preoperative radiation therapy were identified in the National Cancer Database. Patient characteristics, such as age, race, American Joint Committee on Cancer stage, and comorbidity score, were compared between those that received primary radiation only and those that received preoperative radiation with surgery using the χ, Fisher exact, and Mann-Whitney tests as appropriate. Overall survival (OS) by treatment approaches was estimated via the Kaplan-Meier method and compared using the log-rank test. Factors associated with OS were determined using univariate and multivariate Cox proportional hazards regression models., Results: A total of 2046 women were identified; 1407 of these women (69%) received primary radiation therapy (RT; n = 421) or chemoradiation therapy (CRT; n = 986) (RT/CRT), and 639 women (31%) received preoperative RT (n = 92) or CRT (n = 547) followed by surgery (RT/CRT + S). The American Joint Committee on Cancer staging distributions were as follows: T1 (n = 152), T2 (n = 1436), T3 (n = 405), N0 (n = 899), N1 (n = 480), N2 (n = 445), and N3 (n = 40). Median follow-up was 21.9 months. Primary RT/CRT was associated with compromised OS, compared with preoperative RT/CRT + S (41.7% vs 57.1% at 3 years, respectively; P < 0.001). On multivariate analysis, OS associated with primary RT/CRT with doses more than 55 Gy was not significantly different from RT/CRT + S (hazards ratio, 1.139; 95% confidence interval, 0.969-1.338; P = 0.116). Use of concurrent chemotherapy improved OS of primary RT with doses more than 55 Gy compared with CRT + S (hazards ratio, 1.107; 95% confidence interval, 0.919-1.334; P = 0.234)., Conclusions: In a large nationwide analysis, primary nonsurgical management of vulvar cancer with RT was associated with compromised survival compared with preoperative RT with surgery. However, with doses more than 55 Gy and concurrent chemotherapy, nonoperative approaches had comparable survival compared with preoperative CRT + S.

Objectives: This study aimed to evaluate clinical outcomes after chemoradiation (CRT) for the definitive (nonsurgical) treatment of vulvar cancer., Materials and Methods: Women with vulvar cancer treated with definitive CRT at a single academic institution between 1994 and 2015 were retrospectively identified. Overall survival (OS), freedom from local recurrence, freedom from distant recurrence, and late toxicities were estimated using the Kaplan-Meier method at 3 years after radiotherapy completion. Univariate Cox regression models were used to estimate the effects of risk factors on these clinical end points. Acute and late toxicities were assessed according to the Common Terminology Criteria for Adverse Events v. 4.0., Results: Twenty-five women met criteria for inclusion. At 3 years, OS was 71% (95% confidence interval [CI], 49%-93%), freedom from local recurrence was 65% (95% CI, 43%-87%), and freedom from distant recurrence was 78% (95% CI, 59%-97%). Older age was significantly associated with decreased OS (hazard rate, 1.069/y; 95% CI, 1.005-1.124; P = 0.035) and local recurrence (hazard rate, 1.077/y; 95% CI, 1.009-1.150; P = 0.026). Larger size of the primary was borderline associated with distant recurrence (P = 0.057). Skin changes were the most common late toxicity, with a 3-year rate of late G3 skin toxicity of 45% (95% CI, 20%-69%). The rate of lymphedema at 3 years was 25% (95% CI, 5%-44%)., Conclusions: Definitive CRT for advanced vulvar cancer was an effective and well-tolerated approach for women with unresectable disease. Further work is needed to more appropriately select women who will benefit most from a nonsurgical approach.