title: Prospective study of HPV16 viral load and risk of in situ and invasive squamous cervical cancer.
abstract: BACKGROUND
  A strong association has been shown between high viral DNA load (VL) of human papillomavirus (HPV) type 16 and risk for cervical cancer in situ (CIS). However, little data is available for the significance of VL in invasive squamous cell carcinoma (SCC).
  
  
  METHODS
  In 2 nested case-control studies among women participating in cervical screening, with a cytologically normal first smear, we collected 5,665 smears from 621 women with CIS, 457 with SCC, and individually matched controls. All smears were tested for HPV, and VLs of HPV16 positive smears were quantified using real time-PCR. The median follow-up until diagnosis of CIS or SCC was 6.1 to 7.7 years.
  
  
  RESULTS
  Low VL's were common among both CIS and SCC case women, until 1 to 2 years before diagnosis when a surge in VL occurred. The relative risk (RR) associated with low viral load of HPV16 was around 10 for CIS, and 10 to 20 for SCC throughout 10 years before diagnosis, compared with HPV16-negative women. For women with medium to high VL, the risk for CIS was greatly increased from 5 years before diagnosis [RR, 19; 95% confidence interval (CI), 7-48]. In SCC, a high VL conferred an increased risk, but only from 3 years before diagnosis [RR, 60; 95% CI, 6-580].
  
  
  CONCLUSIONS
  We show differing risk functions associated with HPV16 viral load in CIS and SCC, respectively. We further show that viral loads were unexpectedly low early in the SCC disease process.
  
  
  CONCLUSIONS
  HPV16 viral load appears highly complex which may limit its use in cervical screening.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, P.O. Box 281, S-171 77 Stockholm, Sweden. karin.sundstrom@ki.se
authors.forename: Karin
authors.initials: K
authors.lastname: Sundström
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploner
authors.forename: Lisen Arnheim
authors.initials: LA
authors.lastname: Dahlström
authors.forename: Juni
authors.initials: J
authors.lastname: Palmgren
authors.forename: Joakim
authors.initials: J
authors.lastname: Dillner
authors.forename: Hans-Olov
authors.initials: HO
authors.lastname: Adami
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ylitalo
authors.forename: Pär
authors.initials: P
authors.lastname: Sparén
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D002278:Carcinoma in Situ / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D016022:Case-Control Studies; D005260:Female; D052162:Human papillomavirus 16 / Q000302:isolation & purification*; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000453:epidemiology*; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D018570:Risk Assessment; D013548:Sweden / Q000453:epidemiology; D014412:Tumor Virus Infections / Q000175:diagnosis / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000821:virology*; D014626:Vaginal Smears; D019562:Viral Load; D055815:Young Adult