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Association of human papilloma virus status and response to radiotherapy in vulvar squamous cell carcinoma
  1. Lily Proctor1,
  2. Lien Hoang2,
  3. Jocelyn Moore3,
  4. Emily Thompson2,
  5. Samuel Leung4,
  6. Divya Natesan5,
  7. Junzo Chino5,
  8. Blake Gilks2 and
  9. Jessica N McAlpine1
  1. 1 Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada
  2. 2 Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
  3. 3 Radiation Oncology, BC Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada
  4. 4 Genetic Pathology Evaluation Center, Vancouver General Hospital, Vancouver, British Columbia, Canada
  5. 5 Radiation Oncology, Duke University School of Medicine, Durham, North Carolina, USA
  1. Correspondence to Dr Jessica N McAlpine, Obstetrics and Gynecology, The University of British Columbia, Vancouver, BC V5Z 1M9, Canada; jessica.mcalpine{at}


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.

  • radiotherapy
  • vulva
  • vulvar neoplasms
  • pathology
  • radiation oncology

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  • Contributors LP, LH, CBG and JNM contributed to conceptualization and writing of manuscript. All authors were involved in the editing and approval of the final manuscript and/or contribution of tissues.

  • Funding Division of Gynecologic Oncology at the University of British Columbia for funding support.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.