A matched comparison of human papillomavirus-induced squamous cancer of unknown primary with early oropharynx cancer

Laryngoscope. 2018 Jun;128(6):1379-1385. doi: 10.1002/lary.26965. Epub 2017 Oct 31.

Abstract

Objectives/hypothesis: Patients with human papillomavirus (HPV)-induced cancer of unknown primary (CUP) are generally excluded from clinical trials, despite surgical series reporting detection rates of occult oropharynx primaries of >80%. We performed a matched-pair analysis to compare outcomes between T0N1-3M0 HPV+ CUP and T1-2N1-3M0 HPV+ oropharynx known primary (OPX).

Study design: Retrospective cohort study at a single institution.

Methods: Patients with early T stage, node positive HPV+ OPX or CUP treated with curative intent between 1998 and 2016 were identified. For a subgroup of CUP patients with an unknown HPV status, we imputed HPV status and included patients with a >80% probability of being HPV+. Cohorts were matched based on patient demographics using a nearest neighbor propensity technique. After matching, patients were grouped according to either a favorable or unfavorable risk stratification designations per current NRG Oncology clinical trial enrollment criteria. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan-Meier analysis.

Results: Of 298 patients with T1-2N1-3 OPX, 48 were matched to 48 HPV+ CUP patients (32 with confirmed and 16 imputed HPV status). Median follow-up for CUP (34.1 months) and OPX (27.8 months) patients were similar (P = .23).There were no significant differences between the CUP and OPX groups for 3-year DFS (89% vs. 85%, P = .44), and 3-year OS (91% vs. 91%, P = .11), respectively.

Conclusions: Patients with T0N+M0 HPV-induced CUP have similar survival outcomes to matched patients with T1-2N+M0 HPV+ OPX. These patients can reasonably be included in clinical trials investigating the role of treatment deintensification and risk stratified similar to patients with early-stage known primary OPX cancer.

Level of evidence: 4. Laryngoscope, 128:1379-1385, 2018.

Keywords: Cancer of unknown primary; human papillomavirus; oropharyngeal cancer; squamous cell carcinoma; unknown primary.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / mortality*
  • Carcinoma, Squamous Cell / therapy
  • Carcinoma, Squamous Cell / virology
  • Cause of Death
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasms, Unknown Primary / mortality*
  • Neoplasms, Unknown Primary / therapy
  • Oropharyngeal Neoplasms / mortality*
  • Oropharyngeal Neoplasms / therapy
  • Oropharyngeal Neoplasms / virology
  • Papillomaviridae
  • Papillomavirus Infections / complications*
  • Prognosis
  • ROC Curve
  • Retrospective Studies
  • Survival Analysis
  • Treatment Failure