Evaluation of the attributable fraction and burden of HPV-related oropharyngeal cancers in Greece-the ORPHEAS study

Abstract

Background: Herein, we evaluated the attributable fraction (AF) of human papillomavirus (HPV)-mediated (HPV+) oropharyngeal carcinomas (OPCs) in Greece over a recent calendar period.

Patients and methods: ORPHEAS, a retrospective, observational, multicenter, cross-sectional study with prospective recruitment, included adult patients with OPC in 2017-2022, each of them with a high-quality, treatment-naïve tumor specimen. The primary endpoint was the HPV-AF, defined as combined positivity for p16^INK4a (p16) overexpression and HPV DNA presence by central laboratory testing, among included patients. Other endpoints evaluated the HPV+/HPV- patient/disease characteristics at OPC diagnosis and the HPV subtypes for HPV+ patients.

Results: 144/147 patients with available HPV status by central laboratory testing were analyzed [median age: 60.0 years; males: 111 (77.1%)]. The most common tumor anatomical sites were the tonsils (70/147, 48.6%) and the base of the tongue (51, 35.4%), and most patients were at the American Joint Committee on Cancer eighth edition TNM (tumor-node-metastasis) stages III (25, 22.7%) and IV (43, 39.1%). The HPV-AF was 52.1% (75/144; 95% confidence interval 43.6% to 60.5%). Most HPV+ patients were infected by an HPV type targeted by the 9-valent HPV vaccine (72/75, 96.0%), especially HPV16 (70/75, 93.3%). HPV+ compared with HPV- patients were younger (median age 58.0 versus 64.0 years; P = 0.003); more likely to have tumors in the tonsils (65.0% versus 30.4%; P < 0.001); less likely to have tumors in the base of the tongue (25.3% versus 46.4%; P = 0.008); and less frequently at TNM stage IV (20.4% versus 57.1%; overall P < 0.001).

Conclusions: In Greece, we observed a high HPV-AF (52.1%) in OPC, approximating the AFs reported for some Northern European countries. HPV+ versus HPV- patients were younger, more frequently with tonsillar tumors, and less frequently at TNM stage IV. Since most patients were infected by ≥1 HPV type targeted by the 9-valent vaccine, the HPV+ OPC burden could be mitigated through a routine HPV gender-neutral vaccination program.

Keywords: Greece; attributable fraction; human papillomavirus; oropharyngeal cancer; patient profile.

Figure 1

HPV-AF for all patients with available HPV status by central laboratory and by sensitivity analyses 1 and 2.^a,b AF, attributable fraction; OPC, oropharyngeal carcinoma; HPV, human papillomavirus. ^aThe attributable fraction was the proportion of patients with OPC and HPV+ tumor samples divided by the total number of patients with OPC and available HPV status (i.e. p16 expression and HPV DNA) by central laboratory testing. HPV+ tumor samples were defined as those with combined positivity for p16 expression and HPV DNA. ^bIn sensitivity analysis 1, patients with discordant HPV status (HPV+/HPV−) between the medical records and the central laboratory test results were excluded. In sensitivity analysis 2, patients with discordant HPV DNA and p16 expression results by central laboratory testing were excluded.

Figure 2

Treatment patterns for patients with OPC at diagnosis (N = 125) by therapeutic class (A), by therapeutic class and HPV status (B), and by therapeutic class and OPC tumor stage at diagnosis (C).^a,b HPV, human papillomavirus; N, number of all patients included in the analysis; n, number of patients by subgroup; OPC, oropharyngeal carcinoma. ^aPatients could have received ≥1 treatment class. ^bP values in the comparisons for immunotherapy and targeted therapy are not shown in Figure 2B and C as the number of patients in these categories was insufficient for meaningful inferences.