Journal article
Genomic and Molecular Profiling of Human Papillomavirus Associated Head and Neck Squamous Cell Carcinoma Treated with Immune Checkpoint Blockade Compared to Survival Outcomes
Cancers, Vol.13(24), p.6309
12/16/2021
DOI: 10.3390/cancers13246309
PMCID: PMC8699559
PMID: 34944929
Abstract
Simple Summary The prognosis of recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) remains poor. However, human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) patients live longer than those that are negative for HPV infection. In addition, some R/M HNSCC patients respond well to immune checkpoint blockade (ICB) therapies including pembrolizumab and nivolumab, but whether HPV infection is correlated with a good response to ICB is unclear. Here we attempt to understand if ICB treatment improves survival outcomes of HPV and/or surrogate marker p16-positive OPSCC and non-OP HNSCC. We also investigate other potential biomarkers and mutations that may predict improved response to ICB in both HPV-positive and -negative HNSCC patients. With better biomarkers, future treatment can be better tailored to individual patients to improve survival. Recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients overall have a poor prognosis. However, human papillomavirus (HPV)-associated R/M oropharyngeal 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.
Details
- Title: Subtitle
- Genomic and Molecular Profiling of Human Papillomavirus Associated Head and Neck Squamous Cell Carcinoma Treated with Immune Checkpoint Blockade Compared to Survival Outcomes
- Creators
- Hira Shaikh - University of CincinnatiJulie E. McGrath - Caris Life SciencesBrittany Hughes - University of CincinnatiJoanne Xiu - Caris Life SciencesPavel Brodskiy - Caris Life SciencesAmmar Sukari - The Barbara Ann Karmanos Cancer InstituteSourat Darabi - Hoag Memorial Hospital PresbyterianChukwuemeka Ikpeazu - University of MiamiChadi Nabhan - Caris Life SciencesWolfgang Michael Korn - Caris Life SciencesTrisha M. Wise-Draper - University of Cincinnati
- Resource Type
- Journal article
- Publication Details
- Cancers, Vol.13(24), p.6309
- Publisher
- Mdpi
- DOI
- 10.3390/cancers13246309
- PMID
- 34944929
- PMCID
- PMC8699559
- ISSN
- 2072-6694
- eISSN
- 2072-6694
- Number of pages
- 13
- Language
- English
- Date published
- 12/16/2021
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984695829302771
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