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. 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.
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.
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.
Authors: Beata Biesaga; Anna Mucha-Małecka; Anna Janecka-Widła; Marta Kołodziej-Rzepa; Sława Szostek; Dorota Słonina; Aleksandra Kowalczyk; Krzysztof Halaszka; Marcin Przewoźnik Journal: J Cancer Res Clin Oncol Date: 2017-10-17 Impact factor: 4.553
Authors: Mariel A Oyervides-Muñoz; Antonio A Pérez-Maya; Celia N Sánchez-Domínguez; Anais Berlanga-Garza; Mauro Antonio-Macedo; Lezmes D Valdéz-Chapa; Ricardo M Cerda-Flores; Victor Trevino; Hugo A Barrera-Saldaña; María L Garza-Rodríguez Journal: Viruses Date: 2020-03-31 Impact factor: 5.048