Feasibility of Immunohistochemical p16 Staining in the Diagnosis of Human Papillomavirus Infection in Patients With Squamous Cell Carcinoma of the Head and Neck: A Systematic Review and Meta-Analysis

Human papillomavirus (HPV) is a risk factor for squamous cell carcinoma of the head and neck (HNSCC). This study aimed to investigate the feasibility of IHC- p16INK4a (p16) as an alternative modality for diagnosing HPV infection. We searched PubMed, EMBASE, Web of Science, and Cochrane library for studies that evaluated the diagnostic accuracy of IHC-p16 staining. A total of 30 studies involving 2,963 patients were included from 2007 to 2019. The combined sensitivity was 0.94 (95% CI: 0.92-0.95); specificity, 0.90 (95% CI: 0.89-0.91); positive likelihood ratio (LR), 6.80 (95% CI: 5.63-8.21); negative LR, 0.10 (95% CI: 0.07-0.16); diagnostic odds ratio, 85.98 (95% CI: 55.57-133.03); and area under the curve value, 0.9550. Subgroup analysis showed that the IHC-p16 test was more consistent with the in situ hybridization (ISH) test and has greater diagnostic value for oropharyngeal squamous cell carcinoma. The diagnostic efficacy of IHC-p16 varied among countries. In conclusion, IHC-p16 has high sensitivity and specificity for diagnosing HPV infection in HNSCC. The consistency of IHC-p16 findings with those of ISH indicate that their combination can be used to improve the specificity of diagnosis.