Differential diagnosis of synchronous double primary squamous cell carcinomas of the esophagus and occult primary oropharynx through HPV testing: A case report.

Rationale: Esophageal and head and neck cancers often coexist due to field cancerization, which causes multiple squamous cell carcinomas (SCCs) in the upper aerodigestive tract. However, guidelines for the differential diagnosis and optimal treatment of synchronous esophageal and head and neck SCC are lacking. This study highlights the diagnostic and therapeutic challenges of these coexisting malignancies.

Patient Concerns: A 52-year-old man presenting with dysphagia was diagnosed with esophageal SCC, and an incidental retropharyngeal tumorous lesion was found during staging.

Diagnoses: Biopsy revealed SCC in both lesions. To differentiate between metastatic disease and a second primary SCC, immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed. The retropharyngeal SCC showed strong p16 staining, indicating human papilloma virus (HPV)-related origin, while the esophageal SCC was p16-negative. NGS revealed distinct genetic profiles for each lesion, confirming synchronous double primary SCCs.

Interventions: The patient underwent definitive concurrent chemoradiotherapy for both SCCs.

Outcomes: The patient achieved a complete response for both lesions and remains recurrence-free 1 year after treatment.

Lessons: This case underscores the importance of HPV testing and/or NGS in patients with multiple SCCs in the upper aerodigestive tract to accurately differentiate primary cancers from metastases.