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

Huanhuan Wang; Yuyu Zhang; Wei Bai; Bin Wang; Jinlong Wei; Rui Ji; Ying Xin; Lihua Dong; Xin Jiang

doi:10.3389/fonc.2020.524928

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

Front Oncol. 2020 Nov 25:10:524928. doi: 10.3389/fonc.2020.524928. eCollection 2020.

Authors

Huanhuan Wang^{1

2

3}, Yuyu Zhang^{1

2

3}, Wei Bai⁴, Bin Wang^{1

2

3}, Jinlong Wei^{1

2

3}, Rui Ji⁵, Ying Xin⁶, Lihua Dong^{1

2

3}, Xin Jiang^{1

2

3}

Affiliations

¹ Department of Radiation Oncology, The First Hospital of Jilin University, Changchun, China.
² Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun, China.
³ NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, China.
⁴ Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, China.
⁵ Department of Biology, Valencia College, Orlando, FL, United States.
⁶ Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China.

Abstract

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.

Keywords: human papillomavirus; immunohistochemical staining; meta-analysis; p16; squamous cell cancers of the head and neck.

Publication types

Systematic Review