Individuals With HPV-Positive Oropharynx Cancer Likely to Have Pathologic ENE, Positive Margins Following TORS


Patients who received transoral robotic surgery for human papillomavirus–positive oropharynx squamous cell carcinoma were likely to experience pathologic extra nodal extension and positive margins following surgery.

Transoral robotic surgery in a population of patients with have human papillomavirus (HPV)–positive oropharynx squamous cell carcinoma (OPSCC) who did not have obvious extra nodal extension (ENE) were likely to experience pathologic ENE or positive surgical margins following treatment, according to a study published in JAMA Otolaryngology-Head and Neck Surgery.

Notably, the proportion of pathologic ENE appeared to vary across clinical N categories, including 0% for cN0, 16.7% for cN1, 13.0% for cN2a, and 35.6% for cN2b. Patients with cN2b had higher odds of pathologic ENE compared with cN1 to cN2 (OR, 3.01; 95% CI, 1.14-8.10). Additionally, clinical and pathological N category were concordant (55.6%) although 30.9% of patients were upstaged and 12.5% were downstaged.

Within the patient population (n = 136), 113 patients were men with a the median age of 63 years. A total of 52.9% patients were former or current smokers. Additionally, 39.7% patients had cT1 disease and 68.4% had cN2b disease. The majority of patients (80.1%) had at least 1 adverse histopathologic event, 25.0% patients had either a pathologic ENE or primary surgical margin, 2.2% patients had both.

The most common adverse features were a single positive node larger than 3 cm (15.4%) patients, multiple positive nodes (11.0%), and LVI (5.1%). The most frequent combination among 30 patients with 2 adverse features included multiple positive nodes with a positive node larger than 3 cm (7.4%), and multiple nodes with pathologic ENE (5.1%).

Investigators were not able to establish an association between cN2b vs cN1 to cN2a with positive surgical margins (OR, 0.94; 95% CI, 0.14-5.14), LVI (OR, 1.29; 95% CI, 0.50-3.25), or

perineural invasion (OR, 2.09; 95% CI, 0.42-11.1).

Presurgical factors such as age of 65 years or older (OR, 1.14; 95% CI, 0.44-2.89; OR, 0.92; 95% CI, 0.18-4.10), smoking history of at least 20-pack years (OR, 2.28; 95% CI, 0.77-6.35; OR, 2.59; 95% CI, 0.49-11.79), heavy alcohol consumption (OR, 1.42; 95% CI, 0.36-4.70; OR, 1.50; 95% CI, 0.14-8.39), clinically known vs unknown tumors (OR, 0.63; 95% CI, 0.21-1.73; OR, 0.20; 95% CI, 0.004-1.54), base of tongue vs tonsil primary site (OR, 1.96; 95% CI, 0.62-6.94; OR, 2.80; 95% CI, 0.49-28.94), and cT2 vs cT0 to cT1 disease (OR, 2.31; 95% CI, 0.85-6.08; OR, 1.21; 95% CI, 0.19-5.66) were found in pathologic ENE or primary surgical margins, respectively.

According to AJCC-7, clinicopathologic concordance occurred in 70 patients based on T category and 77 patients based on N category. Among the 136 patients who had cT0 to cT2 disease, only 3 (2.2%) were upstaged to pT3, which met a possible indication for adjuvant therapy.

Of the 6. 3% of patients with cN0, 1 were upstaged and 62.5% of patients with cN1 were upstaged to pN2a or greater, which met the indication for possible adjuvant therapy. Among patients with cN0, cN1, and cN2a disease who were upstaged to pN2b, 1 patient with cN0 disease, 17 with cN1, and 2 with cN2a had 2 nodes identified.


Zebolsky AL, George E, Gulati A, et al. Risk of pathologic extranodal extension and other adverse features after transoral robotic surgery in patients with HPV-positive oropharynx cancer. JAMA Otolaryngol Head Neck Surg. Published Online October 21, 2021. doi:10.1001/jamaoto.2021.2777

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