title: Interactions Between High- and Low-Risk HPV Types Reduce the Risk of Squamous Cervical Cancer.
abstract: BACKGROUND
  The clinical significance of co-infections with high-risk (HR) and low-risk (LR) human papillomavirus (HPV) in the etiology of cervical cancer is debated, as prospective evidence on this issue is limited. However, the question is of increasing relevance in relation to HPV-based cancer prevention.
  
  
  METHODS
  In two population-based nested case-control studies among women participating in cervical screening with baseline normal smears, we collected 4659 smears from women who later developed cancer in situ (CIS; n = 524) or squamous cervical cancer (SCC; n = 378) and individually matched control subjects who remained free of disease during study follow-up. The median follow-up until diagnosis was 6.4 to 7.8 years. All smears were tested for HPV. We used conditional logistic regression models with two-way interaction terms to estimate relative risks (RRs) for CIS and SCC, respectively. All statistical tests were two-sided.
  
  
  RESULTS
  Compared with women who were infected with HRHPV only, women who were also infected with LRHPV had a lower risk for SCC (RR = 0.2, 95% confidence interval [CI] = 0.04 to 0.99, P = .049). This interaction was not shown for CIS (RR = 1.1, 95% CI = 0.4 to 3.6). Women who were positive for both HRHPV and LRHPV had, on average, a 4.8 year longer time to diagnosis of SCC than women who were positive for HRHPV only (P = .006). Results were highly robust in sensitivity analyses.
  
  
  CONCLUSIONS
  Co-infection with LRHPV is associated with a lower risk of future invasive disease and longer time to diagnosis than infection with HRHPV alone. We propose that co-infection with LRHPV interferes with the rate of progression to invasive cervical cancer.
authors.affiliation: Department of Laboratory Medicine (KS, JD), Department of Medical Epidemiology and Biostatistics (AP, LAD, JP, HOA, PS, JD), and Department of Medicine, Clinical Epidemiology Unit (SE), Karolinska Institutet, Stockholm, Sweden; Swedish eScience Research Center, Stockholm, Sweden (JP); Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland (JP); Department of Epidemiology, Harvard School of Public Health, Boston, MA (HOA); Division of Clinical Cancer Epidemiology, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden (NYH). karin.sundstrom@ki.se.
authors.forename: Karin
authors.initials: K
authors.lastname: Sundström
authors.affiliation: Department of Laboratory Medicine (KS, JD), Department of Medical Epidemiology and Biostatistics (AP, LAD, JP, HOA, PS, JD), and Department of Medicine, Clinical Epidemiology Unit (SE), Karolinska Institutet, Stockholm, Sweden; Swedish eScience Research Center, Stockholm, Sweden (JP); Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland (JP); Department of Epidemiology, Harvard School of Public Health, Boston, MA (HOA); Division of Clinical Cancer Epidemiology, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden (NYH). karin.sundstrom@ki.se.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploner
authors.affiliation: Department of Laboratory Medicine (KS, JD), Department of Medical Epidemiology and Biostatistics (AP, LAD, JP, HOA, PS, JD), and Department of Medicine, Clinical Epidemiology Unit (SE), Karolinska Institutet, Stockholm, Sweden; Swedish eScience Research Center, Stockholm, Sweden (JP); Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland (JP); Department of Epidemiology, Harvard School of Public Health, Boston, MA (HOA); Division of Clinical Cancer Epidemiology, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden (NYH).
authors.forename: Lisen
authors.initials: L
authors.lastname: Arnheim-Dahlström
authors.affiliation: Department of Laboratory Medicine (KS, JD), Department of Medical Epidemiology and Biostatistics (AP, LAD, JP, HOA, PS, JD), and Department of Medicine, Clinical Epidemiology Unit (SE), Karolinska Institutet, Stockholm, Sweden; Swedish eScience Research Center, Stockholm, Sweden (JP); Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland (JP); Department of Epidemiology, Harvard School of Public Health, Boston, MA (HOA); Division of Clinical Cancer Epidemiology, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden (NYH).
authors.forename: Sandra
authors.initials: S
authors.lastname: Eloranta
authors.affiliation: Department of Laboratory Medicine (KS, JD), Department of Medical Epidemiology and Biostatistics (AP, LAD, JP, HOA, PS, JD), and Department of Medicine, Clinical Epidemiology Unit (SE), Karolinska Institutet, Stockholm, Sweden; Swedish eScience Research Center, Stockholm, Sweden (JP); Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland (JP); Department of Epidemiology, Harvard School of Public Health, Boston, MA (HOA); Division of Clinical Cancer Epidemiology, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden (NYH).
authors.forename: Juni
authors.initials: J
authors.lastname: Palmgren
authors.affiliation: Department of Laboratory Medicine (KS, JD), Department of Medical Epidemiology and Biostatistics (AP, LAD, JP, HOA, PS, JD), and Department of Medicine, Clinical Epidemiology Unit (SE), Karolinska Institutet, Stockholm, Sweden; Swedish eScience Research Center, Stockholm, Sweden (JP); Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland (JP); Department of Epidemiology, Harvard School of Public Health, Boston, MA (HOA); Division of Clinical Cancer Epidemiology, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden (NYH).
authors.forename: Hans-Olov
authors.initials: HO
authors.lastname: Adami
authors.affiliation: Department of Laboratory Medicine (KS, JD), Department of Medical Epidemiology and Biostatistics (AP, LAD, JP, HOA, PS, JD), and Department of Medicine, Clinical Epidemiology Unit (SE), Karolinska Institutet, Stockholm, Sweden; Swedish eScience Research Center, Stockholm, Sweden (JP); Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland (JP); Department of Epidemiology, Harvard School of Public Health, Boston, MA (HOA); Division of Clinical Cancer Epidemiology, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden (NYH).
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ylitalo Helm
authors.affiliation: Department of Laboratory Medicine (KS, JD), Department of Medical Epidemiology and Biostatistics (AP, LAD, JP, HOA, PS, JD), and Department of Medicine, Clinical Epidemiology Unit (SE), Karolinska Institutet, Stockholm, Sweden; Swedish eScience Research Center, Stockholm, Sweden (JP); Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland (JP); Department of Epidemiology, Harvard School of Public Health, Boston, MA (HOA); Division of Clinical Cancer Epidemiology, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden (NYH).
authors.forename: Pär
authors.initials: P
authors.lastname: Sparén
authors.affiliation: Department of Laboratory Medicine (KS, JD), Department of Medical Epidemiology and Biostatistics (AP, LAD, JP, HOA, PS, JD), and Department of Medicine, Clinical Epidemiology Unit (SE), Karolinska Institutet, Stockholm, Sweden; Swedish eScience Research Center, Stockholm, Sweden (JP); Institute for Molecular Medicine Finland, Helsinki University, Helsinki, Finland (JP); Department of Epidemiology, Harvard School of Public Health, Boston, MA (HOA); Division of Clinical Cancer Epidemiology, Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden (NYH).
authors.forename: Joakim
authors.initials: J
authors.lastname: Dillner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000453:epidemiology / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000821:virology*; D016022:Case-Control Studies; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000150:complications* / Q000821:virology; D016133:Polymerase Chain Reaction; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000821:virology*; D014626:Vaginal Smears
chemical_list: D004279:DNA, Viral