Possibilities for the early diagnosis of head and neck squamous cell carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a diverse group of cancers originating from the mucosal linings of the oral cavity, oropharynx, hypopharynx, and larynx. Globally, HNSCC is the sixth most common type of cancer, presenting significant health challenges due to its late-stage diagnosis, which often leads to poor prognosis and reduced quality of life. Principal risk factors for HNSCC include chronic consumption of alcohol and tobacco, with additional factors such as betel nut chewing contributing significantly in certain regions like Central and South Asia. Despite advancements in treatment modalities, the late detection of HNSCC remains a critical issue, highlighting the urgent need for effective early diagnosis and screening methods. Early diagnosis involves both “screening” asymptomatic individuals and “case detection” in patients with identified lesions. This review comprehensively examines the current methodologies and updates in early diagnosis practices for HNSCC.

Methods

This systematic review adheres to the PRISMA guidelines and encompasses a thorough search of databases including PubMed, Science Direct, Google Scholar, and the Cochrane Register. The literature reviewed spans publications from 2006 to 2022, employing search terms like “prevention,” “screening,” “early diagnosis,” “head and neck cancer,” and “general practitioner.” Excluded from this review are articles focusing on specialized HNSCC management, ensuring a focus on early diagnosis and screening practices.

Oral Cancers (OCs)

Oral cancers (OCs), as categorized by the International Classification of Diseases for Oncology, involve malignancies of the inner lips, tongue, gums, palate, oral mucosa, and floor of the mouth. In 2020, OCs represented 2% of all new cancer cases and accounted for 1.8% of global cancer deaths. The highest incidence rates are observed in regions such as India, Sri Lanka, Pakistan, Bangladesh, and Papua New Guinea. The risk factors for OCs vary by region, with betel nut chewing being predominant in Asia, while tobacco and alcohol consumption, poor dental hygiene, and genetic predispositions are more significant in Europe and Oceania.

Precancerous lesions in OCs include leukoplakia, erythroplakia, and verrucous hyperplasia, which can potentially progress to malignancy. Several screening methods are employed for the early detection of OCs:

• Conventional Examination: This involves a straightforward visual inspection and palpation of the oral cavity, serving as a non-invasive primary screening tool.
• Self-examination: Currently, there is insufficient evidence supporting the effectiveness of self-examination for organized screening programs.
• Toluidine Blue Staining: This method selectively stains cancerous tissues, though its sensitivity and specificity vary, necessitating further validation.
• Exfoliative Cytology: This technique collects cells from mucosal surfaces, demonstrating sensitivity and specificity ranges from 76.8% to 88.9%.
• Salivary Biomarkers: These non-invasive tests hold promise but are limited by the timing and protocols for sample processing.
• Blood Biomarkers: Moderately sensitive markers such as carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCCAA), and cytokeratin fragment (CYFRA) are used.
• Cell-free DNA Biomarkers: The presence of tumor DNA in circulation presents a potential early detection tool.
• Autofluorescence Imaging: This method differentiates healthy from cancerous tissues based on fluorophore distribution.
• Light-based Detection Systems: Various light methods are employed to identify mucosal changes, though further validation is required for widespread adoption.

Oropharyngeal Cancers (OPCs)

Oropharyngeal cancers (OPCs), which affect areas such as the base of the tongue, tonsils, and oropharyngeal walls, comprised 0.5% of new cancer cases and 1% of cancer deaths in 2020. The incidence of HPV-positive OPCs is increasing in developed countries, contrasting with a decline in HPV-negative cases. Key risk factors include alcohol and tobacco use, betel nuts, HPV infection, and having multiple sexual partners. Screening methods for OPCs include:

• Tonsillar Swabs: These have proven ineffective for HPV detection.
• Serological Tests: These tests target HPV antibodies, although not all HPV-positive cancers result in seropositivity.

Laryngeal Cancer

Laryngeal cancer accounted for 1% of new cancer cases and deaths worldwide in 2020. The primary risk factors are heavy tobacco and alcohol use, with some cases linked to HPV infection. The early stages of laryngeal cancer are classified according to the AJCC/UICC TNM system. Early diagnosis methods for laryngeal cancer involve techniques similar to those used for OCs and OPCs, including visual examinations, biomarker detection, and imaging technologies.

Conclusions

Early diagnosis of HNSCC is imperative due to the high morbidity and mortality associated with advanced-stage detection. While various screening methods are available, their effectiveness varies, necessitating ongoing research and the development of standardized protocols to enhance early detection. Improved early diagnostic practices will significantly impact patient outcomes, reducing the burden of HNSCC and enhancing quality of life.

Full text

The study was recently published in the Cancer Screening and Prevention.

Cancer Screening and Prevention (CSP) publishes high-quality research and review articles related to cancer screening and prevention. It aims to provide a platform for studies that develop innovative and creative strategies and precise models for screening, early detection, and prevention of various cancers. Studies on the integration of precision cancer prevention multiomics where cancer screening, early detection and prevention regimens can precisely reflect the risk of cancer from dissected genomic and environmental parameters are particularly welcome.

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