Background: Human papilloma virus (HPV) related oropharyngeal squamous cell cancer (OPSCC) is a recently discovered clinical entity that is clinically and biologically distinct from tobacco and alcohol-related cancer. HPV-positive tumors have a favorable prognosis and respond better to chemotherapy, radiation and chemo-radiation. Retrospective studies have suggested that the pattern of failure is different between the HPV-negative (neg) and positive (pos) cohorts, with loco-regional failure being more common with the former and distant metastases (DM) with latter. Patients with smoking and alcohol-related head and neck (HN) cancer have increased incidence of second primary malignancies (SPM) in the HN or lung due to field cancerization. However, the incidence and sites SPM in patients with HPV pos OPSCC are not well characterized. Our primary aims were to study the differences in rate and pattern of synchronous and metachronous SPM in HPV pos and neg OPSCC, and to study the differences in rate and pattern of recurrent disease in HPV pos and neg OPSCC.
Methods: Charts of patients with OPSCC diagnosed between 2012 and 2014 with minimum follow up of 2 years were reviewed. Data collected included age, gender, stage of disease, smoking history, location of primary disease, presence of synchronous or metachronous SPM, and site(s) and timing of disease recurrence. HPV status was determined by P16 immuohistochemistry. Descriptive statistics were used to summarize the data.
Results: 91 patients were included. There was male predominance (77%) and median age was 60 years. Primary sites included base of tongue (n=45), tonsil (37), soft palate (2), and not specified (7). By stage, 58 were IV, 19 were III, one stage II, two stage I, and 11 had missing staging information. 70 patients were HPV pos and 21 HPV neg. The majority received definitive chemoradiation. Relapse occurred in 11 HPV pos (16%) and 14 HPV neg patients (67%) [OR 0.09, CI 0.03-0.28, P<0.01]. Nine out of 11 HPV pos relapses (81%) were DM whereas 4/14 (28%) patients in the HPV neg group had DM [OR 11.25, CI 1.64-76.85, P=0.01]. Twelve HPV pos patients and 6 HPV neg had synchronous or metachronous SPM [OR 0.45, CI 0.14-1.41, P= 0.17]. Of the 6 HPV neg patients with SPM, 4 were second HN primaries and one lung adenocarcinoma. All of the 12 HPV pos patients had SPM in sites other than the HN or lung: specifically, skin, hematologic, thyroid, renal and cervical cancers.
Conclusion: The incidence of relapse, patterns of failure and SPM differ meaningfully in HPV-pos and neg OPSCC. Unlike in the HPV neg group, HPV pos relapses and SPM often occur in sites other than HN and lung. These observations may have implications for disease surveillance and should be validated in larger, prospective studies.