Independent association of marijuana use and poor oral hygiene with HPV–negative but not HPV–positive head and neck squamous cell carcinomas

Abstract

BACKGROUND: Sexual behavior is associated with human papillomavirus (HPV)-positive head and neck cancer, whereas tobacco and alcohol use are associated with HPV-negative cancer. A case-control study was designed to investigate additional demographic and behavioral factors independently associated with these distinct oral cancers. METHODS: From 2011 to 2014, 249 newly diagnosed oral cavity and oropharyngeal squamous cell carcinoma (OSCC) cases were matched (1:2) on age, gender, and self-identified race to 498 controls without a cancer history attending the outpatient otolaryngology clinic at The Ohio State University in Columbus. Cases were stratified by detection of high-risk HPV DNA and RNA in tumors. Demographic and behavioral data were collected using an audio computer-assisted self-interview, and associations with HPV-positive versus HPV-negative OSCCs were investigated by use of univariable and multivariable conditional logistic regression models. RESULTS: After adjustment for oral sexual behavior, the odds of HPV-positive cancer decreased with the patient's years of education. Annual income, tobacco smoking, alcohol drinking, marijuana smoking, and poor oral hygiene were not associated with HPV-positive OSCC. In contrast, the odds of HPV-negative OSCC increased independently with decreased annual income, decreased with a high number of marijuana hit-years, and increased with fewer than annual dental visits after adjustment for lifetime tobacco and alcohol use. Sexual behavior and education were not associated with HPV-negative OSCC. CONCLUSIONS: The distinct risk-factor profiles for HPV-positive and HPV-negative OSCC are confirmed and extended in this case-control study, thus supporting 2 principal etiological pathways for OSCC development.

Relevance of Human Papillomaviruses in Head and Neck Cancer—What Remains in 2021 from a Clinician’s Point of View?

“…The gold standard for the detection of biologically active, thus carcinogenic, HPV infections is the analysis of E6/E7 mRNA by RT PCR, with very high sensitivity and specificity [ 36 , 43 ]. Compared to p16 INK4A IHC, this method might have the disadvantage that it requires sample preparations of the tissue DNA and mRNA.…”

“…We repeatedly have carried out studies following the latter recommendation and believe to have generated the most reliable and reproducible results with the highest avoidance of misclassification. It seems that a growing number of scientists rather shift from primarily p16 INK4A IHC-based to mRNA-PCR-based detection methods, as only recently shown by Shewale and co-workers still addressing this approach as gold-standard [ 36 ].…”

“…Infection and cancer were most common in men between 40 and 59 years who had never smoked or were former smokers. Just recently, a case control study on HPV-positive and -negative OPSCC was published, strongly proposing a significant correlation between riskier sexual behavior and HPV-positive tumors as well as between tobacco and alcohol consumption and HPV-negative tumors [ 36 ]. Thus, according to a considerable amount of data investigating this issue, it seems justified to suggest that HPV-associated diseases in the head and neck should be addressed as STD, also, with the latter certainly being correlated to riskier sexual behavior.…”

“…Therefore, and due to other differences in study populations based on the geographical area the study population is derived from, data from US-American study populations might possibly not easily be transferred to other study populations. In fact, Shewale and co-workers [ 36 ] pointed out that due to lesser racial diversity, their hospital-based study conducted in Ohio is not even representative for the general US population.…”

TIGIT as a therapeutic target of HPV-positive head and neck squamous cell carcinomas

“…Recently, a comparison of CD45 + TILs in HPV-positive HNSCC versus HPV-negative HNSCC with scRNA-Seq revealed distinct CD4 + T cell, B cell, and myeloid cell phenotypic states in the HPV-positive HNSCC versus HPV-negative HNSCC (9), suggesting unique immunomodulatory dependencies. Therefore, immunotherapy combinations may be differentially effective in tumors caused by persistent HPV infection in contrast to chronic carcinogen exposure (e.g., tobacco and alcohol) (10).…”