title: Prognostic significance of human papillomavirus viral load in correlation with different therapeutic modalities in cervical cancer patients.
abstract: OBJECTIVE
  High-risk human papillomavirus (HR-HPV) infections were the causal factor in the development of cervical cancer, but the significance of HPV viral load in the prediction of the response to current therapeutic approaches had not reached consensus. The present study was performed to assess the high risk HPV viral load of cervical cancer patients who underwent radiotherapy alone or in combination with chemotherapy or hyperthermotherapy or both in correlation to long-term survival.
  
  
  METHODS
  116 cervical cancer patients were recruited and assigned into four groups of different therapeutic modalities. The prevalent high risk types of HPV 16, 18, 58 were detected by type specific in situ hybridization (ISH), and HPV mRNA was detected by RNA scope assay using RNA scope 2.0 FFPE Reagent Kit. Semi-quantification of the HR-HPV viral load was measured based on the intensity of ISH signal captured from the tumor nests in the grey scale.
  
  
  RESULTS
  The HR-HPV viral load had a significant negative correlation with survival (rs=-0.368, P=0.001). The 15-year survival rate of low viral load group was 68.18%, moderate viral load group was 52.17%, and high viral load group was 34.69% (P=0.001). HPV mRNA expression was strongly consistent with HPV viral load. The 15-year survival rates of different therapeutic groups were 39.29%, 58.62%, 50.00%, 55.17%, respectively (P=0.545). Combinatorial treatment modalities improved the actual survival, which demonstrated no significant difference among 5, 10 and 15 years comparison. Cox regression analysis showed that the relative risk of death was obviously higher in the HPV 18 single positive group and high HPV viral load group.
  
  
  CONCLUSIONS
  The semi-quantitive viral load assessment in situ is a feasible approach in clinical practice. The more the HPV viral load was, the worse the survival of patients would be. The combinational treatments were in favor of the disease-stabilization.
authors.affiliation: Institute for Cancer Research, School of Basic Medical Science of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi Province, People's Republic of China; Institute for Molecular Radiobiology of Cancer, First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi Province, People's Republic of China; The Key Laboratory of Biomedical Information Engineering, Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, 710049 Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Cao
authors.affiliation: Institute for Cancer Research, School of Basic Medical Science of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi Province, People's Republic of China; Institute of Basic Medical Sciences, Khyber Medical University, 25000 Peshawar, Khyber Pakhtunkhwa, Pakistan.
authors.forename: Walayat
authors.initials: W
authors.lastname: Shah
authors.affiliation: Institute for Cancer Research, School of Basic Medical Science of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi Province, People's Republic of China; The Key Laboratory of Biomedical Information Engineering, Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, 710049 Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Jingxian
authors.initials: J
authors.lastname: Qi
authors.affiliation: Institute for Cancer Research, School of Basic Medical Science of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi Province, People's Republic of China; Department of Pathology, Xi'an Medical University, 710021 Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute for Cancer Research, School of Basic Medical Science of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi Province, People's Republic of China. Electronic address: wangyili@mail.xjtu.edu.cn.
authors.forename: Yili
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute for Molecular Radiobiology of Cancer, First Affiliated Hospital of Xi'an Jiaotong University, 710061 Xi'an, Shaanxi Province, People's Republic of China. Electronic address: chenhwdr@hotmail.com.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Chen
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D011379:Prognosis; D011878:Radiotherapy; D015996:Survival Rate; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D019562:Viral Load
chemical_list: D000970:Antineoplastic Agents
keywords: Cervical cancer; Comprehensive treatment; Human papillomavirus; Overall survival; Viral load