Objectives: Syphilis is a resurging disease which can present itself in many ways, including lesions within the head and neck mucosa. Some of these lesions may clinically mimic oral malignancies. This literature review aims to better characterize the mucosal presentations of syphilis. Methods: PubMed, EMBASE, and clinicaltrials.gov were searched for full-text, English articles published from 1950 to 2022 that reported patients with head and neck mucosal manifestations of syphilis. Articles were screened according to PRISMA guidelines. Results: One hundred forty-three manuscripts documenting 236 individual patients were included in the review. Patients with secondary syphilis accounted for 62% of patients presenting with head and neck mucosal lesions. The most common lesions found in primary and secondary syphilis were ulcerations, primarily found on the tongue, lips, and palate. While serologic studies are the gold standard for diagnosing syphilis, biopsy of these lesions have characteristic syphilitic changes. Conclusions: Syphilis' nickname of "The great imitator" remains to be true, and the head and neck mucosal manifestations of this disease can resemble commonly seen malignancies. Awareness of this disease and its lesions is prudent given the rising incidence of syphilis within the United States.
Keywords: cancer screening; head and neck; infectious disease; otolaryngology; syphilis.