Besides tobacco use and heavy alcohol consumption, Human Papilloma Virus is recognised as risk factor for bucco/oropharyngeal carcinomas. In 1980s, the virus was estimated to account for 16% of OPSCCs in USA, nowadays its prevalence exceeds 60%. The HPV associated OPSCC is a different clinicopathological entity with better survival results on multimodal therapy. Preliminary results suggest that reduced intensity treatment is non inferior in survival, but better tolerated with less adverse events. We identified different strategies of reducing adverse effects of intensive treatment, as follows.1. Using different fractionation doses in radiotherapy 2. Changing cisplatin to cetuximab in concurrent chemoradiotherapy 3. Using induction chemotherapy, followed by reduced dose chemoradiation 4. Surgery followed by deintensified chemoradiotherapy. Many radiation, chemotherapy de-escalation trials and minimally invasive surgical techniques are being evaluated. It is important to identify the ideal patient group for treatment deintensification and to define prognostic risk groups to avoid undertreating.