title: Physical state & copy number of high risk human papillomavirus type 16 DNA in progression of cervical cancer.
abstract: OBJECTIVE
  High-risk human papilloma virus (HR-HPV) infection and its integration in host genome is a key event in malignant transformation of cervical cells. HPV16 being a dominant HR-HPV type, we undertook this study to analyze if viral load and physical state of the virus correlated with each other in the absence of other confounding variables and examined their potential as predictors of progressive cervical lesions.
  
  
  METHODS
  Both, viral load and integration status of HPV16 were determined by real time URR PCR and estimation of E2:E6 ratio in a total of 130 PGMY-RLB -confirmed, monotypic HPV16-infected cervical DNA samples from biopsies of cytology-confirmed low grade (LSIL, 30) and high grade (HSIL, 30), and invasive carcinoma, (squamous cell carcinoma SCC, 70) cases.
  
  
  RESULTS
  Investigation of DNA samples revealed a gradual increase in HPV16 viral load over several magnitudes and increased frequency of integration from LSIL to HSIL and HSIL to invasive cancer in relation to the severity of lesions in monotypic HPV16-infected cervical tissues. In a substantial number of precancer (11/60) and cancer cases (29/70), HPV16 was detected in concomitant mixed form. The concomitant form of HPV16 genome carried significantly higher viral load.
  
  
  CONCLUSIONS
  Overall, viral load and integration increased with disease severity and could be useful biomarkers in disease progression, at least, in HPV16-infected cervical pre-cancer and cancer lesions.
authors.forename: Shirish
authors.initials: S
authors.lastname: Shukla
authors.forename: Sutapa
authors.initials: S
authors.lastname: Mahata
authors.forename: Gauri
authors.initials: G
authors.lastname: Shishodia
authors.forename: Shailja
authors.initials: S
authors.lastname: Pande
authors.forename: Gaurav
authors.initials: G
authors.lastname: Verma
authors.forename: Suresh
authors.initials: S
authors.lastname: Hedau
authors.forename: Suresh
authors.initials: S
authors.lastname: Bhambhani
authors.forename: Archana
authors.initials: A
authors.lastname: Kumari
authors.forename: Swaraj
authors.initials: S
authors.lastname: Batra
authors.forename: Seemi F
authors.initials: SF
authors.lastname: Basir
authors.forename: Bhudev C
authors.initials: BC
authors.lastname: Das
authors.affiliation: Division of Molecular Oncology, Institute of Cytology & Preventive Oncology (ICMR), Noida, India.
authors.forename: Alok C
authors.initials: AC
authors.lastname: Bharti
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000503:physiopathology / Q000821:virology*; D056915:DNA Copy Number Variations / Q000502:physiology*; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D060888:Real-Time Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000503:physiopathology / Q000821:virology*; D019562:Viral Load; D016662:Virus Integration / Q000502:physiology*
chemical_list: D015415:Biomarkers