A shifting paradigm in the aetiology of oral and pharyngeal cancer in Sri Lanka: a case-control study providing serologic evidence for the role of oncogenic HPV types 16 and 18

BACKGROUND: Oral and pharyngeal cancer (OPC) of multifactorial aetiology is a major health problem globally. Ranking first in all cancers, OPC poses a significant impact on the Sri Lankan male population. As Human Papillomavirus (HPV) high risk (HR) types are found to be significant risk factors for OPC globally, the current study was undertaken to examine the association between HR-HPV16 and 18 types with OPC in Sri Lanka. MATERIALS AND METHODS: Serum samples of 78 OPC patients and 51 non-cancer controls were assayed for the presence of anti-HPV16 and anti-HPV18 IgG antibodies using in-house established Enzyme Linked Immunosorbent Assays (ELISAs). The association between OPC and its risk factors i.e. HPV, smoking, alcohol, betel quid, poor dentition, was established using Chi-square test. Logistic regression was used to calculate odds ratios (OR), adjusted for the influence of other risk factors. RESULTS: This prototype study in Sri Lanka showed a significant risk of 15 fold in developing OPC due to HPV16/18 seropositivity after removing variability due to other factors. Oncogenic HPV18 showed a higher rate of seropositivity being detected in 32% of OPC patients, and also in 2% of non-cancer control subjects. HR-HPV16 was detected in 23% of OPC patients and in 5.88% of controls. Moreover, seven OPC patients were detected with both anti-HPV16 and anti-HPV18 antibodies. According to the logistic regression models HPV18 seropositivity was associated with a 28 fold risk in developing OPC while that of HPV16 was associated with a 6 fold increase in risk for the development of OPC. A 5 fold risk of developing OPC was also pronounced among smokers while alcohol, betel and poor dentition was not significantly associated with OPC. Statistically significant differences with regard to age, gender, smoking, alcohol, betel use, poor dentition and site specificity of the tumour was not observed between HPV seropositive and seronegative OPC patients. CONCLUSIONS: Both in-house developed ELISAs detected significant proportions of HPV seropositives within the OPC study population suggestive of HPV as a strong risk factor for oral and pharyngeal carcinogenesis in Sri Lanka.