Coexistence of high-risk HPV infection and FANCC heterozygous variation in early young esophageal squamous cell carcinoma: a case report and literature review

Abstract

<title>Abstract</title> <bold>Background:</bold> Esophageal cancer poses a major health challenge in China, with current screening targeting individuals over 40. However, rising incidence in younger populations, often with atypical symptoms, leads to delayed diagnosis. Investigating the underlying causes in this group is urgently needed. <bold>Case Introduction:</bold> We report a case of a 28-year-old male with early esophageal squamous cell carcinoma presenting with nonspecific abdominal distension and diarrhea. Lesions were identified using magnifying endoscopy with narrowband imaging and treated via endoscopic submucosal dissection (ESD). Postoperative pathology confirmed carcinoma in situ. Molecular analysis revealed high-risk HPV 16/18 infection and whole exome sequencing showed DNA repair gene alterations, including heterozygous FANCC variants. A review of 12 PubMed cases of patients under 30 highlighted varied and atypical presentations, often diagnosed at advanced stages with poor prognosis. <bold>Conclusion:</bold> This case supports more proactive endoscopic evaluation in young individuals with risk factors, beyond age-based screening. The coexistence of high-risk HPV infection and FANCC gene variations suggests a potential viral-genetic synergy in early-onset esophageal cancer.