IntroductionVulvar 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.MethodsThis 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.ResultsForty-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).ConclusionThis 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.

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5528 Background: Cervical cancer is the leading cause of cancer mortality of women in Low and Middle Income Countries (LMIC). Interstitial needles (IN) have improved outcomes but the resources required in comparison to intracavitary brachytherapy (IC) alone has impeded uptake in endemic regions. We conducted a retrospective review of the utilisation of IN in the management of locally advanced cervical cancer and simulated 2D planning by loading the applicators using standard Manchester loading (ML) to explore the magnitude of benefit that interstitial needles provide. Methods: 72 brachytherapy plans of 18 patients who had undergone treatment using tandem and ring and had interstitial brachytherapy between 04/2016 and 10/2018 were reviewed. ML plans prescribed to point A were generated to represent a 2D scenario but the known HR-CTV was taken into consideration and its dosimetric outcomes were compared to those of the 3D based plans. Results: The median tumour volume was 23 cm3. IN was used in 82 % of the insertions. The median number of IN was 2 (range 0 – 6) with median percentage of IN dwell time 6.6 % (range 0.68 – 38.5). V100 was excellent 98.2% for ML 97.3% for 3D IN and 98.7% for 3D non-IN plans. The median HRCTV D90 was 8.5 Gy/fraction (cumulative EQD210101.4 Gy) for ML plans and 8.0 Gy/fraction (cumulative EQD210 91.4 Gy) for 3D plans. The ML plans failed to meet the OAR goals except for the rectum, which was optimally distanced by the rectal paddle. The median bladder, sigmoid and small bowel doses were 24% above the recommended constraint in the individual plans and 15% cumulative EQD2. A statistically significant relationship was found between the number of needles utilised, tumour volume (p < 0.001) and coverage (p = 0.006) but not delivered dose (p < 0.068). Conclusions: 2D brachytherapy can provide adequate dose coverage for most tumours but IN provide a benefit in reducing the doses to OARs in a significant number of patients. This justifies investment in resources for uptake of interstitial needles to increase access to optimal treatment of cervical cancer for women in LMIC. This research was made possible an ASCO Conquer Cancer Foundation grant.