Article

Molecular Profiling Identifies Potential Prognostic Biomarker for Treatment Response in HNSCC

Author(s):

Human papillomavirus surrogate marker p16 was identified as a potential prognostic biomarker for standard-of-care immune checkpoint blockade therapy response in non-oropharyngeal head and neck squamous cell carcinoma.

Real-world overall survival among patients with oropharyngeal squamous cell carcinoma (OPSCC) and non-OP head and neck squamous cell carcinoma (HNSCC) differed significantly based on the presence of the human papillomavirus (HPV) surrogate marker p16, with further implications identified regarding time on treatment with immune checkpoint blockade (ICB) therapies. Findings were published in Cancers.

Identified as the sixth most common cancer worldwide with incidence expected to increase by 32% in the next 2 decades, patients with recurrent and/or metastatic HNSCC typically have a poor prognosis.

Although diagnosis of HNSCC is typically related to tobacco and alcohol use, incidence of HPV-associated HNSCC has risen substantially, in which those positive for the virus whose HNSCC stems in the oropharynx have exhibited better survival outcomes.

Researchers sought to further investigate the association of HPV and/or its surrogate marker p16 with response to standard-of-care ICB therapies in patients with OPSCC and non-oropharyngeal (non-OP) HNSCC.

“We also investigated other potential biomarkers and mutations that may predict improved response to ICB in both HPV-positive and -negative patients with HNSCC,” they added.

Patients registered in the Caris Life Sciences CODEai database with non-OP HNSCC and OPSCC were recruited and identified by comprehensive molecular profiling to be positive or negative for p16. In total, 2905 HNSCC (OPSCC, n = 948) cases were identified.

Of those tested for both HPV directly and p16, 32% (251/791) were p16-positive and 28% (91/326) were HPV-positive. Among patients with OPSCC, the most common mutation was TP53 (33%), followed by PIK3CA (17%) and KMT2D (10.6%), in which TP53 mutations were more common in p16-negative (49%) vs p16-positive patients (10%; P < .0005).

Aligned with prior findings, real-world overall survival (OS) was found to be longer in p16-positive vs p16-negative patients with OPSCC (33.3 vs 19.1 months; HR, 0.597; P = .001). Real-world OS was also significantly longer in p16-positive vs p16-negative patients with non-OP HNSCC (34 vs 17 months; HR, 0.551; P = .0001).

No difference in the time on treatment (TOT) was identified in ICB-treated patients with OPSCC who were p16-positive or -negative (4.2 vs. 2.8 months; HR, 0.796; P = .221). Conversely, p16-positive patients with non-OP HNSCC treated with ICB exhibited higher TOT compared with the p16-negative group (4.3 vs 3.3 months; HR, 0.632; P = 0.016), which researchers said indicates that p16 may be used as a prognostic biomarker in non-OP disease.

“In the future, these results may help guide treatment decisions and provide a rationale for further investigation,” concluded the study authors. “Clinical trials with large patient populations are required to assess whether p16 and other potential biomarkers can predict ICB treatment response.”

Reference

Shaikh H, McGrath JE, Hughes B, et al. Genomic and molecular profiling of human papillomavirus associated head and neck squamous cell carcinoma treated with immune checkpoint blockade compared to survival outcomes. Cancers (Basel). Published online December 16, 2021. doi:10.3390/cancers13246309

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