title: Immunodeficiency and the risk of cervical intraepithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV cohort study.
abstract: HIV-infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100-cell/μL decrease = 1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR = 1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use = 0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Gary M
authors.initials: GM
authors.lastname: Clifford
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Franceschi
authors.affiliation: Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.
authors.forename: Olivia
authors.initials: O
authors.lastname: Keiser
authors.affiliation: Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.|Swiss HIV Cohort Study, Coordination and Data Center, Lausanne, Switzerland.
authors.forename: Franziska
authors.initials: F
authors.lastname: Schöni-Affolter
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Mauro
authors.initials: M
authors.lastname: Lise
authors.affiliation: Cancer Registry of the Cantons of Zurich and Zug, Zurich, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dehler
authors.affiliation: Cancer Registry of the Cantons of Vaud and Neufchatel, Lausanne, Switzerland.
authors.forename: Fabio
authors.initials: F
authors.lastname: Levi
authors.affiliation: Cancer Registry of Basel, Basel, Switzerland.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Mousavi
authors.affiliation: Cancer Registry of the Canton of Geneva, Geneva, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Bouchardy
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Aline
authors.initials: A
authors.lastname: Wolfensberger
authors.affiliation: Service of Infectious Diseases, Vaud University Hospital, Lausanne, Switzerland.
authors.forename: Katharine E
authors.initials: KE
authors.lastname: Darling
authors.affiliation: Department of Infectious Diseases, Unit HIV/AIDS, Bern University Hospital and University of Bern, Bern, Switzerland.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Staehelin
authors.affiliation: Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.|Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital of St Gallen, St Gallen, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bertisch
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors.forename: Esther
authors.initials: E
authors.lastname: Kuenzli
authors.affiliation: Regional Hospital, Lugano, Switzerland.
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.affiliation: Department of Genome Modifications and Carcinogenesis, Infection and Cancer Program, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Pawlita
authors.affiliation: Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.|Centre for Infectious Disease Epidemiology and Research (CIDER), University of Cape Town, Rondebosch, Cape Town, South Africa.
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D015994:Incidence; D016017:Odds Ratio; D013557:Switzerland; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000276:immunology*; D002578:Uterine Cervical Dysplasia / Q000453:epidemiology / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents
keywords: HIV; cervical cancer; cervical neoplasia; human papillomavirus; immunodeficiency