Human papillomavirus 16/18 E7 viral loads predict distant metastasis in oral cavity squamous cell carcinoma

Chung-Guei Huang; Li-Ang Lee; Kuo-Chien Tsao; Chun-Ta Liao; Lan-Yan Yang; Chung-Jan Kang; Kei-Ping Chang; Shiang-Fu Huang; I-How Chen; Shu-Li Yang; Li-Yu Lee; Chuen Hsueh; Tse-Ching Chen; Chien-Yu Lin; Kang-Hsing Fan; Tung-Chieh Chang; Hung-Ming Wang; Shu-Hang Ng; Tzu-Chen Yen

doi:10.1016/j.jcv.2014.07.007

Human papillomavirus 16/18 E7 viral loads predict distant metastasis in oral cavity squamous cell carcinoma

J Clin Virol. 2014 Oct;61(2):230-6. doi: 10.1016/j.jcv.2014.07.007. Epub 2014 Jul 22.

Authors

Chung-Guei Huang¹, Li-Ang Lee², Kuo-Chien Tsao³, Chun-Ta Liao⁴, Lan-Yan Yang⁵, Chung-Jan Kang², Kei-Ping Chang², Shiang-Fu Huang², I-How Chen², Shu-Li Yang³, Li-Yu Lee⁶, Chuen Hsueh⁶, Tse-Ching Chen⁶, Chien-Yu Lin⁷, Kang-Hsing Fan⁷, Tung-Chieh Chang⁷, Hung-Ming Wang⁸, Shu-Hang Ng⁹, Tzu-Chen Yen¹⁰

Affiliations

¹ Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; Department of Medical Biotechnology and Laboratory Science, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC.
² Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
³ Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
⁴ Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Otorhinolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC. Electronic address: liaoct@cgmh.org.tw.
⁵ Departments of Biostatistics and Informatics Unit, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
⁶ Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Clinical Trial Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
⁷ Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
⁸ Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Medical Oncology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
⁹ Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Diagnostic Radiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC.
¹⁰ Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC; Departments of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC. Electronic address: yen1110@cgmh.org.tw.

PMID: 25097016
DOI: 10.1016/j.jcv.2014.07.007

Abstract

Background: Human papillomaviruses (HPV) seem to be related to distant metastasis (DM) in advanced oral cavity squamous cell carcinoma (OSCC) patients.

Objectives: This study aimed to investigate whether high-risk HPV viral load may predict DM among OSCC patients and stratify patients for risk-adapted treatment.

Study design: Viral loads of E7 oncogenes for HPV 16/18 were measured by quantitative PCR tests in paraffin-embedded lesional specimens from 312 OSCC of which the HPV genotypes had been determined previously. Multivariable Cox regression analysis was used to identify the independent prognostic factors for 5-year DM and C statistics were further computed.

Results: By multivariable analysis, high HPV 16 E7 viral load (≥15.0 copies/genome); high HPV 18 E7 viral load (≥15.0 copies/genome); pathological N2 status (pN2); tumor depth ≥11 mm; extracapsular spread (ECS); and level IV/V metastases were independent risk factors for DM. We further identified three prognostic groups. In the high-risk group (level IV/V metastases or high HPV 16/18 E7 viral load plus pN2, tumor depth ≥11 mm, or ECS), the 5-year distant metastasis rate was 74%. In the intermediate-risk group (high HPV 16/18 E7 viral load, pN2, tumor depth ≥11 mm, or ECS), the 5-year DM rate was 17%. Finally, the 5-year DM rate was 1% in the low-risk group (no risk factors). The value of the C statistics was 0.78.

Conclusions: Among OSCC patients, high HPV 16/18 E7 viral load identifies a small subgroup of patients at high-risk of 5-year DM and suggest the need for more intensive treatments and follow-up strategies.

Keywords: Distant metastasis; HPV; HPV 16; Oral cavity squamous cell carcinoma; Outcome; Viral load.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Carcinoma, Squamous Cell / diagnosis*
Carcinoma, Squamous Cell / secondary
Carcinoma, Squamous Cell / virology
DNA-Binding Proteins / genetics
Female
Human papillomavirus 16 / genetics
Human papillomavirus 16 / isolation & purification*
Human papillomavirus 18 / genetics
Human papillomavirus 18 / isolation & purification*
Humans
Male
Middle Aged
Mouth Neoplasms / complications
Mouth Neoplasms / diagnosis*
Neoplasm Metastasis / diagnosis*
Oncogene Proteins, Viral / genetics
Papillomavirus E7 Proteins / genetics
Real-Time Polymerase Chain Reaction
Retrospective Studies
Viral Load*

Substances

DNA-Binding Proteins
E7 protein, Human papillomavirus type 18
Oncogene Proteins, Viral
Papillomavirus E7 Proteins
oncogene protein E7, Human papillomavirus type 16