Emerging insights into recurrent and metastatic human papillomavirus-related oropharyngeal squamous cell carcinoma

Abstract

Objective: To review recent literature on human papillomavirus-related (HPV-positive) oropharyngeal squamous cell carcinoma (OPC) and focus on implications of recurrent and metastatic disease.

Methods: Primary articles from 1990 to 2016 indexed in MEDLINE (1) pertaining to the epidemiology of HPV-positive OPC and (2) providing clinical insight into recurrent and metastatic OPC.

Results: The incidence of HPV-positive OPC is increasing globally. HPV-positive OPC is a subtype with distinct molecular and clinical features including enhanced treatment response and improved overall survival. While disease recurrence is less common in patients with HPV-positive OPC, up to 36% of patients experience treatment failure within eight years. Recurrent and metastatic OPC has historically signified poor prognosis, however recent data are challenging this dogma. Here, we discuss recurrent and metastatic OPC in the context of HPV tumor status.

Conclusion: HPV-positive OPC exhibits distinct genetic, cellular, epidemiological, and clinical features from HPV-negative OPC. HPV tumor status is emerging as a marker indicative of improved prognosis after disease progression in both locoregionally recurrent and distant metastatic OPC.

Level of evidence: N/A.

Keywords: HNSCC; HPV; Head and neck; OPSCC; human papillomavirus; metastatic; oropharyngeal; prognosis; recurrent; squamous cell carcinoma; survival.

Figure 1

Rising prevalence of long‐term oropharyngeal squamous cell carcinoma survivors. Age‐adjusted limited‐duration prevalence (LDP) in 5‐year to 10‐year survivors of oropharyngeal squamous cell carcinoma (OPC). Adapted figure from Patel et al modified with the removal of curves representing overall oral squamous cell carcinoma and oral cavity cancer55.

Figure 2

Site of first progression in HPV‐positive and HPV‐negative oropharyngeal squamous cell carcinoma. Published studies35, 98, 99 describing the first event of recurrence were evaluated to determine the proportion of first recurrence events in OPC representing locoregional recurrence or distant metastatic disease. Patients who experienced local or regional recurrence without distant metastases were categorized as locoregional recurrence (LR). Patients who experienced distant metastasis as the first event of recurrence, with or without concurrent local or regional recurrence, were categorized as distant metastasis (DM). Data was pooled across studies and proportion with LR and DM as first event were calculated and compared by HPV tumor status using chi‐square test (GraphPad Prism 7, La Jolla, CA). Pie charts represent the proportional contribution of locoregional recurrence (LR) and distant metastasis (DM) as the site of first progression in HPV‐positive and HPV‐negative oropharyngeal squamous cell carcinoma (OPC). Based on pooled data from Nguyen‐Tan et al, Guo et al, and Sinha et al35, 98, 99. Patients with synchronous DM and LR were included in the DM subgroup.

Figure 3

Schematic representation of time‐ and survival‐ dependent differences observed in distant metastatic recurrence of HPV‐positive and HPV‐negative oropharyngeal squamous cell carcinoma. Top panel depicts representative survival curves for HPV‐positive and HPV‐negative squamous cell carcinoma (OPC). The two rows below correspond in time course to the survival curve and represent the typical disease course of HPV‐positive and HPV‐negative OPC. Patients with HPV‐positive and HPV‐negative OPC display approximately cotemporaneous distant recurrence40 at common sites (e.g. lung, bone, liver) with the potential presence of additional occult or subclinical distant disease at rare sites (e.g. brain, abdominal lymph nodes, skin). While patients with HPV‐positive OPC show survival durations adequate to display clinically detectable metastasis at rare distant sites, those with HPV‐negative OPC do not.