Elsevier

Oral Oncology

Volume 50, Issue 1, January 2014, Pages 45-51
Oral Oncology

Distant metastasis in p16-positive oropharyngeal squamous cell carcinoma: A critical analysis of patterns and outcomes

https://doi.org/10.1016/j.oraloncology.2013.10.007Get rights and content

Summary

Objective

With good loco-regional control, disease failure in p16-positive oropharyngeal squamous cell carcinoma (OPSCC) mainly results from distant metastasis (DM). Our objective was to characterize the patterns and clinical outcomes of DM in p16-positive OPSCC and compare these to patients with p16-negative disease.

Methods

Primary OPSCC patients who developed DM after completing surgical or non-surgical treatment were identified and p16 status was evaluated. Patterns of DM and post-DM progression-free (PFS) and disease-specific survival (DSS) were assessed.

Results

Forty-one of the 66 (62%) patients with DM were p16-positive. DM patterns were not statistically different by p16 status. However, p16-positive patients developed DM later in their course and had longer survival. All p16-negative patients either had progression or died within 24 months of DM detection whereas the 2-year post-DM PFS in the p16-positive group was 20% (95% CI: 8–32.5%, p = 0.003). The 3-year post-DM disease-specific survival (DSS) estimate in the p16-positive patients was 16% (95% CI: 7–18%) while all p16-negative patients died within 34 months (p < 0.001). p16-negativity, loco-regional disease, and no/palliative versus curative intent treatment were all associated with reduced post-DM DSS in multivariate analysis.

Conclusions

The DM pattern did not differ remarkably between p16-positive and negative OPSCC patients in our practice. In p16-positive OPSCC with pulmonary oligometastatic disease, curative intent treatment and optimized locoregional control for the index primary prolonged survival.

Introduction

Loco-regional control rates are excellent in the majority of p16-positive oropharyngeal squamous cell carcinoma (OPSCC) patients, and poor outcomes are mainly attributable to distant metastasis (DM). The DM rate varies from 5% to 12% in recent non-surgical series of OPSCC with known HPV/p16 status [1], [2], [3], [4], [5], and from 2% to 6% in the surgical series [6], [7], [8], [9]. Emerging reports suggest that the DM patterns for p16-positive patients are atypical compared to those for p16-negative patients. As of now, the only evidence for such an observation comes from two case reports and two cohort studies which have focused on DM patterns in p16-positive OPSCC [5], [10], [11], [12]. The two cohort studies from University of Toronto observed the DM progression in p16-positive OPSCC to more often exhibit a “disseminating” pattern [5], [10]. The second report from this group expanded the study cohort from 36 to 79 patients with DM and reported longer survival in p16-positive patients [5]. All patients in these studies were treated non-surgically.

The rapidly increasing numbers of p16-positive OPSCC at our institution with excellent loco-regional control and failures occurring mainly at distant sites provided the impetus to scrutinize DM patterns in our practice. Our patient population offered a unique opportunity to evaluate DM patterns in OPSCC patients treated both surgically and non-surgically [8].

The primary aim of our study was, therefore, to characterize DM among p16-positive and negative OPSCC patients and to determine if there are any significant differences. Since the data on therapeutic outcomes after DM detection in this era of p16-positive OPSCC is still limited, the second objective of our study was to examine and compare the impact of treatment in both p16-positive and negative cohorts.

Section snippets

Study population

Our institutional review board-approved head and neck cancer surgery and radiotherapy registries were searched for primary OPSCC cases who received treatment at our institution from August 1997 to October 2011. The fundamental inclusion criteria were:

  • 1.

    Previously untreated, biopsy-proven, primary OPSCC (Any T, any N, M0).

  • 2.

    Completion of therapy (surgical or non-surgical) for primary OPSCC.

  • 3.

    Development of DM after completion of therapy, verified by biopsy/resection or serial radiology scans.

  • 4.

    Tissue

Study population

A total of 776 patients were identified from our registries who completed therapy for primary OPSCC. The disease status could not be ascertained for 13 patients, and 4 had DM at the time of primary OPSCC detection, thus leading to 17 exclusions. The remaining 759 patients consisted of 183 (24%) treated non-surgically and 576 (76%) treated surgically. A total of 84 (11%) patients developed DM, 41 (22%) in the non-surgical group and 43 (8%) in the surgical group. Tissue was available for p16 IHC

Discussion

In our study, we observed that p16-positive OPSCC patients develop DM after more prolonged periods following completion of primary treatment compared to p16-negative patients. However, we found that the pattern of DM in the p16-positive patients, although slightly trending towards wider disease spread, as reported in previous studies [17], [20], [21], was not significantly different than the p16-negative patients (p = 0.615). We also noted that DM in p16-positive OPSCC, particularly pulmonary

Conclusions

We have detected a level of survivorship in p16-positive OSPCC patients with DM which approaches 16% at 3 years. If suitable for curative intent treatment, the results were even better, with 40% survivorship at 3 years. By contrast, the majority of p16-negative patients died early in the course after DM detection. In comparison with p16-negative patients who survived long enough to have documented DM progression, the pattern of DM in p16-positive patients did not differ significantly. Our study

Conflict of interest statement

Nothing to declare.

Acknowledgement

Partial support for the study's statistical analysis (Kallogjeri) came from the P30 Research Center for Auditory and Vestibular Studies and the National Institutes of Health (NIDCD Grant #P30 DC04665).

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