Oropharyngeal Treponema pallidum DNA Detection in Early Syphilis: Diagnostic Yield of Pharyngeal PCR and Potential Implications for Mucosal Shedding

Background Syphilis, caused by Treponema pallidum , is a re‐emerging sexually transmitted infection. The oropharynx may be a site of T. pallidum DNA detection, but real‐world data on the diagnostic performance and epidemiological relevance of pharyngeal polymerase chain reaction (PCR) are scarce. Methods We retrospectively analyzed 149 pharyngeal PCR testing episodes from 131 unique patients collected between 2018 and 2025. Seventy‐six testing episodes were classified as syphilis cases, defined by compatible clinical features, serology, and/or PCR positivity at another site, along with 73 controls. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Results were contextualized through a literature review. Results Pharyngeal PCR was positive in 38 of 76 syphilis cases (50%), with a specificity of 100%, positive predictive value (PPV) of 100%, and negative predictive value (NPV) of 65.8%. Positivity rates were 44.4% in primary syphilis, 55.8% in secondary syphilis, 55.6% in early latent syphilis, and 0% in late latent syphilis. Notably, T. pallidum DNA was detected in the pharynx of patients without oral lesions and in some primary syphilis cases with negative rapid plasma reagin (RPR), suggesting possible early oropharyngeal mucosal shedding. In contrast, certain palmoplantar lesions yielded negative PCR results despite concomitant pharyngeal positivity. Conclusions Pharyngeal PCR is a highly specific complementary diagnostic tool, particularly useful in early syphilis and in cases with discordant serology. Detection of T. pallidum DNA in the oropharynx, even without oral lesions, provides evidence of mucosal DNA shedding and suggests potential implications for transmission dynamics. However, PCR does not demonstrate viable organisms, and whether such DNA detection reflects organisms capable of transmission requires further study.