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

Abstract

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.

A case report of thyroid metastasis from p16-positive oropharyngeal squamous cell carcinoma

“…OSCC metastasis to the thyroid gland is a distant metastasis, and the current case was stage IVb T4aN2cM1, according to the tumor-node-metastasis classification. The prognosis of HNSCC with distant metastasis is generally poor [13]; however, compared with HPV-negative OSCC, control of the distant metastatic lesions is reportedly better in HPV-positive OSCC cases [13,18]. Nonetheless, whether the prognosis of HPV-positive OSCC with thyroid gland metastasis is good remains unknown.…”

Reply to B. O'Sullivan et al

“…3 Prior reports had suggested that late, distant metastases were more common among p16-positive patients. [4][5][6] Particular concern was expressed regarding our recommendation for close surveillance within the first 2 years of follow-up. Undoubtedly, surveillance should continue beyond 2 years, 7 as risk of recurrence (albeit lower) persists and second primaries remain possible.…”

Bone Marrow Failure in HPV-Associated Oropharyngeal Squamous Cell Carcinoma

“…Loco-regional control rates are generally excellent amongst p16+ tumours and poor outcomes are mainly attributable to distant metastases [18]. Distant spread is uncommon and usually occurs late in the disease course, typically in the setting of advanced localregional disease [19][20][21].…”

“…A study by Sinha et al set out to characterise the patterns and clinical outcomes of distant metastases in p16+ OPSCC and reported that while the "disseminating" phenotype was almost twice more common than that of the p16-group, the difference was not statistically significant [18]. Rozevick et al [24] report that while HPV positivity is generally felt to be a favorable prognostic indicator, it does not safeguard from spread to the brain.…”