Objectives: The human papillomavirus (HPV) is a risk factor for a subgroup of head and neck cancers (HNC). HPV-positive and HPV-negative HNC patients encompass heterogeneous groups regarding risk factors, sociodemographic and clinical characteristics, which may influence health-related quality of life (HRQL) differently. Since this has been sparsely studied, our study investigated the association between HPV status and HRQL in HNC survivors in Denmark.

Materials and methods: This cross-sectional study included 179 recurrence-free oropharyngeal and oral cavity squamous cell carcinoma (OSCC) survivors. HRQL was assessed on the EORTC QLQ-C30 and QLQ-H&N35 questionnaires. Linear and logistic regression models were adjusted for sociodemographic, clinical and lifestyle factors.

Results: Most unadjusted results showed better HRQL among HPV-positive (n = 119) compared to HPV-negative (n = 60) OSCC survivors (average 18 months since diagnosis). After adjustments, the HPV-positive survivors reported higher role functioning (mean difference [MD] 9.2, 95% confidence interval [CI] 0.1 to -18.4), and fewer problems with speech (MD - 9.0, 95% CI -18.0 to - 0.1), sexuality (MD - 21.9, 95% CI - 38.0 to - 5.9) and opening mouth (MD - 13.7, 95% CI - 26.6 to - 0.8) compared to HPV-negative survivors.

Conclusion: Our findings support that HPV-positive OSCC survivors experience better HRQL than HPV-negative survivors. However, results indicate that sociodemographic, clinical and lifestyle factors explain most of the association between HPV status and HRQL. Findings suggest increased focus on the HPV-negative OSCC survivors with deteriorated HRQL in rehabilitation programs and future research to investigate the long-term effects of treatment among HPV-positive OSCC survivors who may develop symptoms later in survivorship.