Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Background: The prevalence of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) has increased significantly, with HPV now linked to approximately 80-90% of all oropharyngeal cancers. While HPV-positive status is associated with improved prognosis and favorable response to chemoradiation, the incidence of secondary primary cancers (SPCs) in this population remains an area of active research. Although SPCs are generally less common within the oropharyngeal region itself, there is limited data on the incidence and characteristics of SPCs at distant sites in HPV-positive OPSCC patients. Given the increasing number of patients diagnosed with HPV-mediated OPSCC, there is a growing need to understand the patterns, risks, and clinical management of SPCs in both local and distant regions. This review will examine the epidemiology of SPCs in HPV-positive OPSCC, current approaches to surveillance, and considerations for preventive treatment strategies.
Methods: We conducted a comprehensive search across three databases—PubMed, Embase, and the Cochrane Library—from their inception until December 1, 2023, using a combination of free-text terms and controlled vocabulary. To supplement our search, we employed a "snowball" technique, reviewing the reference lists of eligible articles to identify and screen studies that cited them. This systematic review and meta-analysis followed PRISMA guidelines. We included studies reporting on secondary primary cancers following oropharyngeal cancer, focusing on outcomes such as the incidence of secondary primary cancers (SPC), sites of SPC, survival rates, treatment patterns, and demographic information.
Findings: A total of more than >16,000 patients were included in the review. The pooled incidence of second primary OPSCC was 1.7% whereas pooled incidence of any SPC was 4.1%. Incidence of synchronous and metachronous tumors was similar with a ratio of 1:1. The median time to diagnosis for SPC was 4.7 years. Distant site SPC were commonly found by intentional imaging whereas local synchronous tumors were often found incidentally during elective contralateral tonsillectomy. Most common sites of SPC were lungs, head and neck and the gastrointestinal tract.
Conclusion: A thorough examination of the oropharyngeal region should be conducted during both the initial workup and treatment of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). Although secondary malignancies are relatively uncommon, contralateral tonsillectomy and/or biopsies of additional subsites during surgery should be carefully considered, as these procedures do not appear to improve outcomes and increase morbidity. However, the higher incidence of SPCs in distant sites suggests that increased surveillance of these patients is advisable, at least for the first 5 years following surgery.