CONCLUSION No statistically significant 5-year survival difference was seen in patients with oral and oropharyngeal squamous cell carcinoma (OOPSCC) between high-risk HPV-positive and -negative groups in this population-based study. OBJECTIVES To see if the formerly observed higher risk for recurrence or second primary tumour (SPT) in high-risk HPV-positive patients with OOPSCC corresponds to worse survival. METHODS A total of 128 consecutive, previously untreated patients with OOPSCC, who were part of a population-based case-control study in southern Sweden during 2000-2004, were included. A mouthwash sample was collected and exfoliated cells were collected with cotton-tipped swabs from the tonsillar fossa and the tumour. Specimens were analysed for HPV DNA using nested polymerase chain reaction (PCR). Disease-specific survival (DSS) and DSS difference between HPV-negative and HPV-positive patients were calculated. The relationship between age, stage, high-risk HPV status and DSS was assessed. Oral and oropharyngeal tumours were assessed separately. RESULTS Mean DSS in months was 80.7/68.6 (high-risk HPV-negative/high-risk HPV-positive) for oral cavity tumours (p = 0.18) and 67.6/78.3 (high-risk HPV-negative/high-risk HPV-positive) for oropharyngeal tumours (p = 0.47). For oral cavity tumours, age, T status, N status and stage all showed significant differences in DSS. For oropharyngeal tumours, no significant difference regarding DSS was found.