Predictors for Survival of Patients with Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Region.

Simple Summary: Human papillomavirus (HPV) association is the most important predictor of survival in squamous cell carcinomas in the head and neck region (HNSCC). The role of HPV in cancer of unknown origin at this anatomic site (CUP_HNSCC) is less well understood. The objective of this study was to identify prognostic classification markers in CUP_HNSCC. Therefore, we investigated a consecutive cohort by multivariate modeling and testing for HPV DNA, mRNA, and p16^INK4a (p16) expression. In 31% of CUP_HNSCC, p16 was overexpressed, and high-risk HPV DNA was detected in 18/32 (56.3%) of them, which was mostly consistent with mRNA detection. In contrast to oropharyngeal cancer, detection of p16 without additional detailed HPV testing appears to be more appropriate for the classification of CUP_HNSCC. Three risk groups can be stratified based on performance status and p16, but additional factors may become important in future data or for cases with particular risk profiles. Background: Human papillomavirus (HPV) status is the most important predictor of survival in oropharyngeal squamous cell carcinoma (OPSCC). In patients with cervical lymph node metastases of squamous cell carcinoma of unknown origin (CUP_HNSCC), much less is known. Methods: We assessed a consecutive cohort of CUP_HNSCC diagnosed from 2000–2018 for HPV DNA, mRNA, p16^INK4a (p16) expression, and risk factors to identify prognostic classification markers. Results: In 32/103 (31%) CUP_HNSCC, p16 was overexpressed, and high-risk HPV DNA was detected in 18/32 (56.3%). This was mostly consistent with mRNA detection. In recursive partitioning analysis, CUP_HNSCC patients were classified into three risk groups according to performance status (ECOG) and p16. Principal component analysis suggests a negative correlation of p16, HPV DNA, and gender in relation to ECOG, as well as a correlation between N stage, extranodal extension, and tobacco/alcohol consumption. Conclusions: Despite obvious differences, CUP_HNSCC shares similarities in risk profile with OPSCC. However, the detection of p16 alone appears to be more suitable for the classification of CUP_HNSCC than for OPSCC and, in combination with ECOG, allows stratification into three risk groups. In the future, additional factors besides p16 and ECOG may become important in larger studies or cases with special risk profiles. [ABSTRACT FROM AUTHOR]