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Head and neck cancers are a heterogeneous group of neoplasms, which together comprise the sixth most common cancer globally. Breath biopsies are a non‐invasive clinical investigation that detect volatile organic compounds (VOCs) in exhaled breath. This systematic review examines current applications of breath biopsy for the diagnosis of head and neck squamous cell carcinoma (HNSCC), including data on efficacy and utility, and speculates on the future uses of this non‐invasive detection method. Medline, PubMed, Web of Science, Cochrane and Scopus, as well as the grey literature were searched using a search strategy developed to identify relevant studies on the role of breath biopsy in the diagnosis of HNSCC. All included studies were subject to a thorough methodological quality assessment. The initial search generated a total of 1443 articles, 20 of which were eligible for review. A total of 660 HNSCC samples were investigated across the included studies. 3,7‐dimethylundecane and benzaldehyde were among several VOCs to be significantly correlated with the presence of HNSCC compared to healthy controls. We show that current breath biopsy methods have high accuracy, specificity and sensitivity for identifying HNSCC. However, further studies are needed given the reported poor quality of the included studies. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of the oral cavity (OSCC) is the most common head‐and‐neck malignancy. Importantly, we are experiencing an alarming rise in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) globally. Oncogenic viruses, human papillomavirus (HPV) and Epstein‐Barr virus (EBV), are known to be co‐associated with OSCC and OPSCC cases. However, the reported incidence of HPV and EBV co‐infection in OSCCs and OPSCCs globally is unknown. To address this, we performed a formal meta‐analysis and systematic review on published studies that report the detection of both EBV and HPV in OSCCs and OPSCCs. Our analysis revealed 18 relevant studies out of a total of 1820 cases (1181 from the oral cavity and 639 from the oropharynx). Overall, HPV and EBV co‐infection was found in 11.9% of OSCC and OPSCC cases combined (95% CI: 8%–14.1%). Based on anatomical subsite, dual positivity estimates were 10.5% (95% CI: 6.7%–15.1%) for OSCC and 14.2% (95% CI: 9.1%–21.3%) for OPSCC. The highest dual positivity rates described were in European countries: for OSCC 34.7% (95% CI: 25.9%–44.6%) in Sweden and for OPSCC, 23.4% (95% CI: 16.9%–31.5%) in Poland. Given these substantive prevalence rates, the value of detecting dual infection in the diagnosis and prognosis of these cancers deserves careful longitudinal studies, as do implications for cancer prevention and therapy. We further proposed molecular mechanisms that could explain how HPV and EBV could co‐contribute to the aetiology of OSCCs and OPSCCs. [ABSTRACT FROM AUTHOR]

Though the oral cavity is anatomically proximate to the nasal cavity and acts as a key reservoir of EBV habitation and transmission, it is still unclear whether EBV plays a significant role in oral carcinogenesis. Many studies have detected EBV DNA in tissues and exfoliated cells from OSCC patients. However, very few studies have investigated the expression of functional EBV proteins implicated in its oncogenicity. The most studied are latent membrane protein 1 (LMP-1), a protein associated with the activation of signalling pathways; EBV determined nuclear antigen (EBNA)-1, a protein involved in the regulation of gene expression; and EBV-encoded small non-polyadenylated RNA (EBER)-2. LMP-1 is considered the major oncoprotein, and overexpression of LMP-1 observed in OSCC indicates that this molecule might play a significant role in oral carcinogenesis. Although numerous studies have detected EBV DNA and proteins from OSCC and oral potentially malignant disorders, heterogeneity in methodologies has led to discrepant results, hindering interpretation. Elucidating the exact functions of EBV and its proteins when expressed is vital in establishing the role of viruses in oral oncogenesis. This review summarises the current evidence on the potential role of EBV in oral oncogenesis and discusses the implications as well as recommendations for future research. [ABSTRACT FROM AUTHOR]