HPV-Positive Oropharyngeal Cancer May Mean a Worse Prognosis for Some Patients
By Marilynn Larkin
NEW YORK (Reuters Health) – Although patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) generally have a more favorable prognosis than patients with HPV-negative OPSCC, those with perineural invasion (PNI) or angiolymphatic invasion (ALI) and stage II disease may have poorer outcomes, researchers in Pennsylvania say.
Given the differing outlooks for HPV-positive and HPV-negative OPSCC, the American Joint Committee on Cancer recently updated its staging system (AJCC-8) to reflect separate staging criteria for the two conditions.
“Studies are underway to examine whether radiation and chemotherapy can be reduced in patients with HPV-positive OPSCC without sacrificing overall survival,” Dr. Seungwon Kim of UPMC told Reuters Health.
“Our study showed that there exists a subset of patients with HPV-positive OPSCC that behaves more aggressively, and that these tumors are characterized by PNI and ALI,” he said by email. “In patients with these pathologic features, de-escalation of therapy may not be desirable despite the favorable outcome that is generally expected for patients with HPV-positive OPSCC.”
The team examined the prevalence and prognostic value of PNI and ALI in HPV-positive OPSCC, and used this same cohort to test the external validity of the new AJCC staging system, which is scheduled for implementation in January 2018.
Data were collected retrospectively on all patients with HPV-positive OPSCC who had been treated surgically at the University of Pittsburgh Medical Center from 1980 through 2015, and who had at least one year of follow-up or died within one year.
As reported online October 26 in JAMA Otolaryngology-Head and Neck Surgery, 201 patients (mean age, 57; 80% male) were included.
PNI was identified in 32 (16%) specimens, and ALI was identified in 74 (37%). Both were significantly associated with increasing T stage.
On multivariate analysis, the presence of at least one risk factor (ALI, PNI, or both) was significantly associated with overall (hazard ratio, 2.78) and disease-free survival (HR, 3.10).
Among the 27 patients classified as having stage II disease by the new staging system, the presence of ALI and/or PNI was associated with an 11.7-fold risk for worse overall survival.
“The AJCC-8 pathologic staging system for HPV-positive OPSCC was valid in this patient cohort,” the authors state. “Specifically among patients with AJCC-8 stage II disease, the presence of ALI or PNI may suggest a poorer prognosis.”
Study author Dr. Robert Ferris, also of UPMC, told Reuters Health by email, “Normally, this type of study would lead to a clinical trial. However, we are already in the process of confirming its findings prospectively in an NCI-supported trial (http://bit.ly/2z07slM) that will help us . . . determine when to de-intensify treatment” of stage II patients with HPV-positive OPSCC.
Dr. Erich Sturgis of the University of Texas MD Anderson Cancer Center told Reuters Health by email, “This is important work to improve understanding of how this new staging system works in a surgically treated cohort.”
“No staging system will be perfect nor able to incorporate all important factors affecting survival,” he acknowledged. “This work does suffer from some biases - a single-institution study without a validation cohort. However, it is important for advancing our understanding of other features.”
“Patients treated surgically with PNI and ALI logically would have a worse prognosis,” he said. “But further validation studies in surgically treated patients are encouraged - with prospective collection of such data along with (data on) margin status, degree of extracapsular extension, level of nodal involvement and number of nodes - to better inform clinicians treating such patients.”
Like Dr. Sturgis, Drs. Kenneth Hu and Adam Jacobson of NYU Langone’s Head and Neck Center in New York City told Reuters Health in a joint email that “ALI and PNI are both well-known adverse pathologic risk factors,” and given the findings from previous seminal studies, “presence of ALI and/or PNI would normally be treated with adjuvant radiation alone.”
“Therefore,” they said, “the question arises whether the negative prognostic implication of ALI and/or PNI for stage II patients was consistent in those treated with either radiation alone or chemoradiation.”
They also point to methodological concerns, including short follow-up (median/minimum follow-up is two years in head and neck studies) and the fact that adverse survival outcomes were restricted to stage II patients (only 27 were in the cohort). “Multiple other treatment and pathologic factors could readily confound the results in the small dataset,” they concluded.
Dr. David Cognetti of the Jefferson Center for Head and Neck Surgery in Philadelphia, told Reuters Health, “At Jefferson, we use a very similar treatment strategy to the authors of this study, and when we reviewed our population of patients with HPV-positive OPSCC who underwent transoral robotic surgery, we had similar findings.”
“We also found that the AJCC-8 better reflected patient prognosis, and that survival was most linked to the size of primary tumor (which may reflect this study’s finding of PNI and ALI being more prevalent in larger tumors),” he said. “The information gained from the surgery and pathology report can help personalize the appropriate level of treatment for each patient.”
JAMA Otolaryngol Head Neck Surg 2017.
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