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The tumor genome in human immunodeficiency virus–related head and neck cancer: Exploitable targets?

Population-level data indicate that the age-adjusted incidence rates of head and neck squamous cell carcinoma, a non– AIDS-defining cancer, are elevated in human immunodeficiency virus (HIV)–infected individuals in US, European, and African settings. HIV-infected individuals with head and neck cancer in the United States are significantly less likely to receive any cancer treatment than HIV-uninfected patients; although black race and a lack of insurance are predictors of a failure to receive treatment within this population, HIV infection remains a significant predictor of lack of treatment in a multivariate analysis. Even with treatment, head and neck cancer mortality is increased among the HIV-infected, with a low CD4 count at diagnosis and a prior history of an AIDS-defining illness being associated with increased mortality. Thus, further study of the etiology, natural history, and treatment-responsiveness of head and neck cancer in HIVinfected individuals is urgently needed. The formation of a National Cancer Institute–funded consortium among the head and neck Specialized Program of Research Excellence (SPORE) institutions to pool samples and resources to study these questions and to molecularly characterize head and neck tumors from HIV-infected individuals represents a valuable step forward for the field. In this issue of Cancer, Gleber-Netto et al report on the results of the next-generation sequencing of a panel of 18 head and neck cancer–relevant genes in head and neck cancers from 20 HIV-infected individuals and 32 HIV-uninfected controls. Controls were selected by pathology record review, apparently without systematic serologic confirmation, and thus there is a theoretical possibility that the HIV-negative cohort contained 1 or more individuals with an unrecognized HIV infection. However, it is unlikely that a case with HIV-related immunosuppression and cancer would have remained unrecognized, and thus the clinical relevance of this concern is low. Both human papillomavirus (HPV)–related and -unrelated cancers were included among the HIV-related cases and the HIV-unrelated controls. Among HIV-uninfected individuals, HPV-associated head and neck cancer and HPV-unassociated head and neck cancer are now recognized as essentially distinct diseases with different etiologies, biomolecular signatures, natural histories, and treatment responsiveness. Further risk stratification based on the tumor stage and the patient’s smoking history is possible within HPVrelated head and neck cancer. The cohorts studied in this article, when they were divided by both the HPV status and the HIV status, were quite small, with 11 HPV-negative cancers and 9 HPV-related cancers among the HIV-infected patients, and none of the HPV-related cancers among HIV-infected individuals arose in nonsmokers. For these reasons, the data reported here should be viewed as exploratory, and caution should be exercised to avoid the overinterpretation of numerically small differences in mutation rates in specific genes either between subsets or in comparisons of these data with existing larger sample sets. It is also possible that significant differences in each disease between HIV-infected and HIV-uninfected hosts were not detected in this study. Nonetheless, intriguing results are reported. The authors analyzed the mutation frequency in the genes included in the panel for HPV-related and HPVunrelated subsets in HIV-infected and HIV-uninfected patients and found mutations within the targeted gene panel in the majority of the patients within each subset; this was consonant with the data reported for the head and neck cancer samples in The Cancer Genome Atlas. The variations in the numbers of mutations and the slight differences in the percentages with mutations are of uncertain clinical relevance because of the low numbers. Moreover, germline material was not analyzed, so the possibility of single-nucleotide polymorphisms being classified as tumor-related mutations cannot be excluded.