Head and neck cancer (HNC) is one of the most common cancers worldwide and is still a major public health burden in developing countries. Approximately 750,000 HNC cases and 365,000 HNC-related deaths are reported annually worldwide [1]. Most recent data (2020) from Nepal suggests HNC is a leading contributor to cancer morbidity (2327 new cases, ranking second) and mortality (1070 deaths, ranking fourth) [2]. Previous epidemiological studies have documented significant sex differences in cancer incidence and mortality [3], [4], [5], and have suggested that the consistently higher risk observed among men is likely due to high exposure to well-established risk factors, such as tobacco and alcohol.

A distinct male predominance in the incidence rate is also observed in HNC [6]. Previous studies reported that the associations between modifiable lifestyle factors and HNC risk varied by sex [7], [8]. Tobacco and alcohol consumption are major risk factors for oral cancer, which has been well-established previously. A prospective study conducted in the United States (US) including 584 men and 175 women who developed HNC reported that the hazard ratios (HR) associated with smoking were significantly larger in women (12.96; 95 % confidence interval [CI], 7.81–21.52) than in men (5.45, 95 % CI, 4.22–7.05, p for interaction: <0.001) [9]. Similarly, in another prospective study in the US including 611 men and 183 women who developed HNC, the HR for consuming >3 drinks per day was significantly higher in women (2.52, 95 % CI, 1.46–4.35) than in men (1.48, 95 % 1.15–1.90, p for interaction: 0.0036) [10]. A meta-analysis including 40 studies has reported that secondhand smoking is a significant predictor for overall cancer in women (OR 1.25, 95 % CI 1.14–1.37) and not in men (OR 1.59, 95 % CI 0.91–2.77) [11]. Estrogen exposure may be protective against HNC, with some studies suggesting that the higher risks of HNC among women may be due to estrogen deficiency, menopause, or hysterectomy status [12], [13].

There is a paucity of data assessing the difference in risk factors among men and women in Nepal, which has hindered the development of targeted cancer prevention campaigns among Nepalese women. Given the differences in physiology and lifestyles of both sexes [14], it would be valuable to separately identify the risk factors for HNC in men and women. Therefore, in this large-scale case-control study, we aimed to investigate risk factors of HNC, stratified by sex.