Session Item

To describe the incidence and overall survival (OS) after oropharyngeal carcinoma (OPC), including the relation to Human Papillomavirus (HPV), in a Danish population-based cohort of consecutive patients diagnosed between 1986-2020.

The study cohort was identified in the Danish Head and Neck Cancer database, which has 100% coverage of OPC in Denmark. Data on consecutive Danish patients living in Denmark at the time of OPC diagnosis was prospectively collected and verified in the Danish Cancer Registry. Primary treatment was radiotherapy (66-68 Gy) according to national guidelines with a gradual introduction of radiobiological modifications based on the findings from clinical trials, ie. hypoxic modification and moderately accelerated fractionation in the beginning of the period, and from 2008 concurrent chemoradiotherapy. Tumor-HPV-status was determined on pre-treatment tumor tissue according to p16 immunohistochemistry (p16pos>70% tumor cells).

A total of 8595 patients with stage I-IV OPC were identified, 6324 (74%) men and 2271 (24%) women, with a median age of 60 years. p16-positivity was found in 3530 (41%) of the tumors, whereas 2362 (28%) were p16- and 2703 (31%) had unknown p16-status. Seventy % of patients in the p16+ subgroup were ever smokers (25% current smokers) compared to 97% (71% current smokers) with p16- tumors. During the 35-year time period a threefold increase in the incidence of OPC was observed for both men and women. Simultaneously the frequency of HPV-related p16-positivity among tumors with known p16-status (N=5892) increased from 30% to 70% (Figure 1A). The yearly number of new cases of p16- tumors also increased over time although not to the same extent.  
The 5-year OS probability was 53% in the total cohort, and stratification by p16-status revealed a marked survival benefit in favor of p16-positivity: 76% vs 34% (39% in tumors with unknown p16-status) (Figure 1B). Figure 2 demonstrates the development in 5-year OS over time. For p16+ tumors the survival probability increased from 55% in the beginning of the period to 81% at present (Figure 2A). This development is probably linked up with the intensification of treatment introduced over time, including the use of chemoradiotherapy. Figure 2B illustrates the corresponding development for patients with p16-/p16-unknown tumors. Although improvement in outcome over time has been achieved also for this group of patients, the benefit from intensification of treatment is much less obvious than for p16+ tumors.  

Based on this nationwide cohort of 8595 patients prospectively collected over a period of 35-years, we demonstrate that outcome for Danish patients with OPC has improved significantly from 1986-2020 alongside intensification of treatment. This development is predominantly ascribable to a marked increase in the incidence of HPV-related p16+ tumors combined with their pronounced sensitivity to treatment. However, HPV-negative disease continues to be a therapeutic challenge.