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Randomized Controlled Trial
. 2014 Oct 20;32(30):3365-73.
doi: 10.1200/JCO.2014.55.1937. Epub 2014 Jun 23.

Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma

Carole Fakhry  1 , Qiang Zhang  2 , Phuc Felix Nguyen-Tan  2 , David Rosenthal  2 , Adel El-Naggar  2 , Adam S Garden  2 , Denis Soulieres  2 , Andy Trotti  2 , Vilija Avizonis  2 , John Andrew Ridge  2 , Jonathan Harris  2 , Quynh-Thu Le  2 , Maura Gillison  2
Affiliations
Randomized Controlled Trial

Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma

Carole Fakhry et al. J Clin Oncol. .

Abstract

Purpose: Risk of cancer progression is reduced for patients with human papillomavirus (HPV) -positive oropharynx cancer (OPC) relative to HPV-negative OPC, but it is unknown whether risk of death after progression is similarly reduced.

Patients and methods: Patients with stage III-IV OPC enrolled onto Radiation Therapy Oncology Group trials 0129 or RTOG 0522 who had known tumor p16 status plus local, regional, and/or distant progression after receiving platinum-based chemoradiotherapy were eligible for a retrospective analysis of the association between tumor p16 status and overall survival (OS) after disease progression. Rates were estimated by Kaplan-Meier method and compared by log-rank; hazard ratios (HRs) were estimated by Cox models. Tests and models were stratified by treatment protocol.

Results: A total of 181 patients with p16-positive (n = 105) or p16-negative (n = 76) OPC were included in the analysis. Patterns of failure and median time to progression (8.2 v 7.3 months; P = .67) were similar for patients with p16-positive and p16-negative tumors. After a median follow-up period of 4.0 years after disease progression, patients with p16-positive OPC had significantly improved survival rates compared with p16-negative patients (2-year OS, 54.6% v 27.6%; median, 2.6 v 0.8 years; P < .001). p16-positive tumor status (HR, 0.48; 95% CI, 0.31 to 0.74) and receipt of salvage surgery (HR, 0.48; 95% CI; 0.27 to 0.84) reduced risk of death after disease progression whereas distant versus locoregional progression (HR, 1.99; 95% CI, 1.28 to 3.09) increased risk, after adjustment for tumor stage and cigarette pack-years at enrollment.

Conclusion: Tumor HPV status is a strong and independent predictor of OS after disease progression and should be a stratification factor for clinical trials for patients with recurrent or metastatic OPC.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
CONSORT diagram. RTOG, Radiation Therapy Oncology Group.
Fig 2.
Fig 2.
Kaplan-Meier estimates of overall survival after disease progression for patients with p16-positive and p16-negative oropharyngeal carcinoma (OPC). Patients with p16-positive OPC had significantly better overall survival after disease progression than patients with p16-negative OPC (P < .001). The 2-year rates of overall survival after disease progression were 54.6% for patients with p16-positive OPC (95% CI, 44.9 to 64.4) and 27.6% for patients with p16-negative OPC (95% CI, 17.3 to 37.9).
Fig 3.
Fig 3.
Kaplan-Meier estimates of overall survival after disease progression for patients with p16-positive and p16-negative oropharyngeal carcinoma (OPC) who had (A) locoregional progression, (B) distant metastases, (C) salvage surgery, and (D) no salvage surgery. Patients with p16-positive OPC had significantly better overall survival after disease progression than patients with p16-negative OPC in the subgroups that had locoregional failure (P < .001), distant metastases (P = .04), salvage surgery (P = .004), and no salvage surgery (P = .003).
Fig A1.
Fig A1.
Kaplan-Meier estimates of survival after disease progression for patients with known and unknown p16 tumor status in (A) Radiation Therapy Oncology Group (RTOG) 0129 and (B) RTOG 0522. There are no statistically significant differences in survival after disease progression between patients with known and unknown p16 tumor status in RTOG 0129 (log-rank test, P = .88) or RTOG 0522 (log-rank test, P = .85).
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Comment in

References

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