Human papilloma virus (HPV)-associated head and neck cancer (HNC) has generated significant amount of research interest in recent times with focus shifted to oral cavity squamous cell cancer (OCSCC) after oropharyngeal cancer. Due to high incidence of OCSCC and anecdotal reports on association of HPV infection from northern region of India, this study was conceived to investigate HPV infection and establish its association with lifestyle habits such as tobacco, alcohol consumption, oro-genital sex, number of sexual contacts, and change in quality of life posttreatment. A total of 43 primary OCSCC biopsy specimens were collected. These samples were analyzed for HPV DNA genotyping which was done by using 13 high-risk HPV real-time PCR kits. Quality of life was assessed using University of Washington questionnaire for HNC patients, which was administered pretreatment and 3-months posttreatment. HPV presence was confirmed in only three patients (7.0 %). HPV positivity did not find any statistical correlation with age, gender, residence, addiction habit, stage, tumor size, nodal status, tumor grade, and number of sexual contacts. There was no significant (p > 0.05) difference in the average percent change in QOL parameters from pretreatment to posttreatment when correlated with HPV status.