Previous studies have hypothesized that patients with p16+ oropharyngeal squamous-cell carcinomas presented with higher nodal stages than patients with p16- tumors, and consequently contralateral elective nodal irradiation is needed for p16+ tumors even in early stage disease tonsilar squamous cell carcinomas. The purpose of this study is to validate that hypothesis by analyzing the nodal staging of a cohort of oropharyngeal squamous-cell carcinomas stratified for p16 status.

We included in our study 164 patients with oropharyngeal squamous-cell carcinomas where the p16 status was determined treated between 1998 and 2008. Clinical and radiologics nodal staging were retrospectively analyzed. HPV 16 subtype infection was detected by polymerase chain reaction (PCR). Statistical analysis used to compare our results was performed using Fisher's test.

Of the 164 patients, 112 (68.3%) had p16+ tumors and 52 (31.7%) had p16- tumors. In the p16- and p16+ groups, there were respectively 55.8% and 50.9% tumors of the tonsil and 34.6% and 46.4% tumors of the base of tongue respectively (p=0.054). The tumor stage, according to AJCC 7th edition, was respectively in the p16- and p16+ cohort: T1: 17.36% and 23.2% tumors; T2: 25% and 29.5%; T3: 23.1% and 25.9%; T4: 34.6% and 21.4% with no significant difference between the two groups. There were no significant differences in the nodal staging between the two groups (respectively for p16- and p16+: NO: 3.5% vs 1.8%; N1: 13.5% vs 12.5%; N2a: 13.5% vs 23.2%; N2b: 17,3% vs 23,2%; N2c:17,3% vs 20,5%; N3: 21,1% vs 11,1%). There was no significant difference of nodal staging between the two groups according to the T staging. In the p16- and p16+ groups, there were respectively 28.8% and 25% bilateral lymph nodes involvement. In the p16- and p16+ cohorts, there were respectively 7.7% and 10.7% stage III disease; 67.3% and 74.1% stage IVa; 25% and 15.2% stage IVb without significant difference (p=0.33).

Although numerous ongoing studies are currently exploring dose/volume de-intensification for p16+ oropharyngeal squamous-cell carcinomas, our study suggests caution regarding nodal volume definition as their presentation seems similar regardless of the p16 status. Further studies are warranted to confirm our results.