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Original Investigation |

Association of Extracapsular Spread With Survival According to Human Papillomavirus Status in Oropharynx Squamous Cell Carcinoma and Carcinoma of Unknown Primary Site

Natallia Kharytaniuk, MB1; Peter Molony, MB, MRCPI2; Seamus Boyle, MB1; Gerard O’Leary, MB, FRCSI1; Reiltin Werner, MSc2; Cynthia Heffron, MB, MRCPath2; Linda Feeley, MB, MRCPath2; Patrick Sheahan, MB, FRCSI(ORL-HNS)1
[+] Author Affiliations
1Department of Otolaryngology–Head and Neck Surgery, South Infirmary Victoria University Hospital, Cork, Ireland
2Department of Pathology, Cork University Hospital, Cork, Ireland
JAMA Otolaryngol Head Neck Surg. 2016;142(7):683-690. doi:10.1001/jamaoto.2016.0882.
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Importance  The presence of extracapsular spread (ECS) of metastatic nodes is considered a poor prognosticator in head and neck cancer, with postoperative chemoradiation therapy often recommended over radiation therapy alone in such cases. However, there is less clarity regarding the effect of ECS on human papillomavirus–associated oropharynx squamous cell carcinoma (OPSCC) or carcinoma of unknown primary site (CUP).

Objective  To investigate the association of ECS according to human papillomavirus status in OPSCC and CUP with survival.

Design, Setting, and Participants  This investigation was a retrospective cohort study performed between August 1998 and March 2015 at an academic teaching hospital. Participants were 83 patients with OPSCC (n = 62) or CUP (n = 21) undergoing neck dissection as part of initial treatment.

Main Outcome and Measures  Human papillomavirus status was determined by p16 immunohistochemistry. The presence of ECS was extrapolated from pathology reports, and the extent of ECS was determined by rereview of original pathology slides. Disease-specific survival (DSS) and recurrence-free survival (RFS) were assessed.

Results  Among 83 patients (71 male), there were 45 p16-positive and 38 p16-negative tumors. Fifty-one patients had ECS, which was graded as extensive in 43 cases. The median follow-up was 31 months for all patients and 50 months for surviving patients. Among the entire cohort, adverse predictors of RFS were p16-negative status (hazard ratio [HR], 9.4; 95% CI, 3.3-27.2) and ECS (HR, 6.5; 95% CI, 2.0-21.6). Adverse predictors of DSS were p16-negative status (HR, 16.8; 95% CI, 3.9-71.2) and ECS (HR, 8.3; 95% CI, 2.0-35.3). Among p16-negative patients, ECS was significantly associated with worse RFS (HR, 9.7; 95% CI, 1.3-72.3) and DSS (HR, 8.7; 95% CI, 1.1-62.7). In contrast, among p16-positive patients, ECS had no effect on RFS (HR, 1.1; 95% CI, 0.2-7.8) or DSS (HR, 1.2; 95% CI, 0.1-18.7).

Conclusions and Relevance  The presence of ECS appears to be associated with survival in OPSCC and CUP according to p16 status. Our findings raise questions regarding the benefits of postoperative chemoradiation therapy in p16-positive patients with ECS.

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Figure 1.
Effect of p16 Status in the Entire Cohort

Kaplan-Meier curves show the effect on recurrence-free survival (RFS) and disease-specific survival (DSS). No. at risk, 83.

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Figure 2.
Effect of p16 Status in Patients With Carcinoma of Unknown Primary Site (CUP)

Kaplan-Meier curves show the effect on recurrence-free survival (RFS) and disease-specific survival (DSS). No. at risk, 21.

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Figure 3.
Effect of Extracapsular Spread (ECS) in p16-Negative Patients

Kaplan-Meier curves show the effect on recurrence-free survival (RFS) and disease-specific survival (DSS). No. at risk, 38.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 4.
Effect of Extracapsular Spread (ECS) in p16-Positive Patients

Kaplan-Meier curves show the effect on recurrence-free survival (RFS) and disease-specific survival (DSS). No. at risk, 45.

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