Abstract
Simple SummaryThe 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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) remains the sixth most common cancer worldwide despite recent advances in management, with more than 650,000 cases and 330,000 deaths annually [1]
A total of 2905 HNSCC patients were identified in the Caris database, of which 948 were oropharyngeal squamous cell carcinoma (OPSCC)
Among those who were tested for p16 and/or human papillomavirus (HPV), 32% (251/791) expressed p16 and 28% (91/326) were HPV+
Summary
Head and neck squamous cell carcinoma (HNSCC) remains the sixth most common cancer worldwide despite recent advances in management, with more than 650,000 cases and 330,000 deaths annually [1]. It is predicted that by the year 2040, the worldwide incidence of HNSCC will increase by 32% and mortality by 34% [2]. Larynx, and hypopharynx cancers are often related to tobacco and alcohol. Most human-papillomavirus-positive (HPV+) cancers arise from the oropharynx (OP) [3,4]. Approximately 25% of all HNSCCs are thought to be related to HPV [7]. In the Western world, including the United States and Europe, the incidence of HPV−associated HNSCC has risen substantially, while tobacco- and alcohol-related HNSCC has declined [4,8,9]
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