Genomic and molecular profiling of human papillomavirus associated head and neck squamous cell carcinoma treated with immune checkpoint blockade compared to survival outcomes

Hira Shaikh, Julie E. McGrath, Brittany Hughes, Joanne Xiu, Pavel Brodskiy, Ammar Sukari, Sourat Darabi, Chukwuemeka Ikpeazu, Chadi Nabhan, Wolfgang Michael Korn, Trisha M. Wise-Draper

Research output: Contribution to journalArticlepeer-review

Abstract

Recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients overall have a poor prognosis. However, human papillomavirus (HPV)-associated R/M oropha-ryngeal squamous cell carcinoma (OPSCC) is associated with a better prognosis compared to HPV−negative disease. Immune checkpoint blockade (ICB) is the standard of care for R/M HNSCC. However, whether HPV and its surrogate marker, p16, portend an improved response to ICB remains controversial. We queried the Caris Life Sciences CODEai database for p16+ and p16− HNSCC patients using p16 as a surrogate for HPV. A total of 2905 HNSCC (OPSCC, n = 948) cases were identified. Of those tested for both HPV directly and p16, 32% (251/791) were p16+ and 28% (91/326) were HPV+. The most common mutation in the OPSCC cohort was TP53 (33%), followed by PIK3CA (17%) and KMT2D (10.6%). TP53 mutations were more common in p16− (49%) versus the p16+ group (10%, p < 0.0005). Real-world overall survival (rwOS) was longer in p16+ compared to p16− OPSCC patients, 33.3 vs. 19.1 months (HR = 0.597, p = 0.001), as well as non-oropharyngeal (non-OP) HNSCC patients (34 vs. 17 months, HR 0.551, p = 0.0001). There was no difference in the time on treatment (TOT) (4.2 vs. 2.8 months, HR 0.796, p = 0.221) in ICB-treated p16+ vs. p16− OPSCC groups. However, p16+ non-OP HNSCC patients treated with ICB had higher TOT compared to the p16− group (4.3 vs. 3.3 months, HR 0.632, p = 0.016), suggesting that p16 may be used as a prognostic biomarker in non-OP HNSCC, and further investigation through prospective clinical trials is warranted.

Original languageEnglish (US)
Article number6309
JournalCancers
Volume13
Issue number24
DOIs
StatePublished - Dec 1 2021

Keywords

  • Head and neck squamous cell carcinoma
  • Human papillo-mavirus (HPV)
  • Immune checkpoint blockade
  • Oropharyngeal cancer
  • Outcomes
  • P16
  • Personalized medicine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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