Presence of Human Papillomaviruses in the Normal‐Appearing Hypopharyngeal Mucosa: A Prospective Study

ABSTRACT Objective Human papillomavirus (HPV) is a well‐established etiological factor in oropharyngeal cancer, whereas its role in the hypopharynx is less well understood. This prospective study investigated the prevalence of HPV in normal‐appearing hypopharyngeal mucosa using polymerase chain reaction (PCR)‐based HPV detection. Methods Consecutive patients undergoing hypopharyngoscopy, laryngomicroscopy, or transnasal esophagogastroscopy for benign indications were prospectively recruited. Biopsies were obtained from normal‐appearing hypopharyngeal mucosa and analyzed for HPV DNA by PCR‐based genotyping. Participants completed a questionnaire addressing HPV‐related risk factors. Results Tissue samples were collected from 53 patients (median age, 51 years; range, 18–85 years), of whom 32 (60.4%) were female. One sample was excluded because of insufficient DNA quality. Among the remaining 52 evaluable samples, one was positive for a cutaneous HPV type and one for high‐risk HPV18. The HPV18‐positive sample originated from a patient who was subsequently diagnosed with a p16‐positive squamous cell carcinoma arising in a vallecular cyst. RNA in situ hybridization confirmed transcriptionally active HPV within the tumor. A history of HPV‐associated benign disease was reported by 18 of 53 patients (34%). Conclusion HPV DNA detection was rare in normal‐appearing hypopharyngeal mucosa, even among individuals with a history of HPV‐associated benign disease. Nevertheless, high‐risk HPV18 was detected in the hypopharyngeal mucosa of a patient with an HPV‐positive vallecular squamous cell carcinoma. These findings provide novel data on HPV prevalence in the hypopharynx and suggest that oncogenic HPV may occasionally be present in clinically normal hypopharyngeal mucosa. Level of Evidence 4