Most common cause of squamous cell carcinoma at the base of the tongue is:

Explanation

## Correct Answer: D. HPV **HPV (Human Papillomavirus)** is the most common aetiological agent for squamous cell carcinoma (SCC) at the base of the tongue, particularly HPV-16 and HPV-18 subtypes. The base of the tongue (oropharyngeal region) is lined with stratified squamous epithelium with a rich lymphoid tissue (Waldeyer's ring), making it a prime target for HPV infection. HPV-positive oropharyngeal cancers represent a distinct epidemiological and molecular entity from tobacco/alcohol-related SCCs. In India, the incidence of HPV-associated oropharyngeal SCC is rising, particularly in younger patients without traditional risk factors (smoking/alcohol). The virus integrates into host DNA, disrupting p53 and Rb pathways, leading to malignant transformation. HPV-positive tumours have a better prognosis and different treatment response compared to HPV-negative cancers. The WHO recognizes HPV as a definite carcinogen for oropharyngeal SCC. Vaccination against HPV (quadrivalent/nonavalent) is now recommended in India as part of cervical cancer prevention programmes and increasingly for oropharyngeal cancer prevention in high-risk populations. ## Why the other options are wrong **A. CMV** — CMV (Cytomegalovirus) is an opportunistic pathogen primarily associated with immunocompromised states (HIV/AIDS, post-transplant). It causes mucosal ulceration and oesophagitis but is NOT an established carcinogen for oropharyngeal SCC. NBE trap: students may confuse CMV with other viral causes of oral pathology. **B. EBV** — EBV is associated with nasopharyngeal carcinoma (particularly in Southeast Asian populations) and post-transplant lymphoproliferative disorder, NOT oropharyngeal SCC at the base of tongue. While EBV can be detected in some oral cancers, it is not the primary aetiological agent. NBE trap: conflating EBV's role in nasopharyngeal cancer with oropharyngeal SCC. **C. HCV** — HCV (Hepatitis C Virus) is a hepatotropic virus causing chronic hepatitis and hepatocellular carcinoma, NOT oropharyngeal SCC. While HCV can rarely be detected in oral tissues, there is no established causal link to tongue base SCC. NBE trap: students may confuse HCV's carcinogenic potential (in liver) with other organ sites. ## High-Yield Facts - **HPV-16 and HPV-18** are the high-risk subtypes most commonly associated with oropharyngeal SCC, particularly at the base of tongue. - **Oropharyngeal HPV+ cancers** have better prognosis and improved response to chemoradiation compared to HPV-negative tobacco/alcohol-related cancers. - **HPV integration** disrupts p53 and Rb tumour suppressor pathways, leading to malignant transformation of squamous epithelium. - **Waldeyer's ring lymphoid tissue** at the base of tongue provides a permissive microenvironment for HPV persistence and oncogenic transformation. - **HPV vaccination** (quadrivalent/nonavalent) is now recommended in India as part of cervical cancer prevention and emerging oropharyngeal cancer prevention strategies. - **Rising incidence** of HPV-associated oropharyngeal SCC in India, particularly in younger patients without smoking/alcohol history. ## Mnemonics **OPharyngeal SCC Viruses** **HPV** dominates oropharyngeal SCC (base of tongue); **EBV** → nasopharyngeal SCC (Southeast Asia); **CMV** → immunocompromised mucosal disease; **HCV** → hepatocellular carcinoma (not oropharyngeal). **HPV-Associated Cancers in India** **Cervix** (most common), **Oropharynx** (rising), **Anus**, **Genital** — remember HPV = squamous epithelial surfaces with lymphoid tissue or high turnover. ## NBE Trap NBE pairs oropharyngeal SCC with multiple viral options to test whether students conflate EBV (nasopharyngeal cancer) with oropharyngeal SCC, or confuse HCV/CMV's roles in other organ systems with oropharyngeal carcinogenesis. ## Clinical Pearl In Indian clinical practice, HPV-associated oropharyngeal SCC is increasingly seen in younger patients (30–50 years) without smoking/alcohol history, presenting with dysphagia or neck lymphadenopathy. These tumours respond better to chemoradiation, making HPV status determination critical for treatment planning and prognosis counselling. _Reference: Robbins & Cotran Pathologic Basis of Disease, Ch. 9 (Head & Neck Pathology); Harrison's Principles of Internal Medicine, Ch. 97 (Head & Neck Cancer); Park's Textbook of Preventive & Social Medicine (HPV epidemiology in India)_