title: Persistent human papillomavirus infection is associated with a generalized decrease in immune responsiveness in older women.
abstract: The development of cervical cancer and its precursors are linked to persistent infection with oncogenic types of human papillomavirus (HPV). Host immune responses seem to be determinants of risk for this disease. However, little is known about the immunologic determinants of HPV persistence. Here, we examined the association between lymphoproliferative responses to antigens/mitogens and persistent HPV infection in women older than 45 years. Women included in this study were participants in a 10,000-woman population-based cohort study of cervical neoplasia in Costa Rica. Women older than 45 years and HPV DNA positive at a screening visit were selected as cases (n = 283). We selected a comparably sized control group of HPV DNA-negative women, matched to cases on age and time since enrollment (n = 261). At an additional clinical visit, women were cytologically and virologically rescreened, and cervical and blood specimens were collected. Proliferative responses to phytohemagglutinin (PHA), influenza virus (Flu), and HPV16 virus-like particle (VLP) were lower among women with persistent HPV infection [median counts per minute (cpm): 72,849 for PHA, 1,241 for Flu, and 727 for VLP] than for the control group (median cpm: 107,049 for PHA, 2,111 for Flu, and 2,068 for VLP). The decreases were most profound in women with long-term persistence and were only observed for the oldest age group (>/=65 years). Our results indicate that an impairment in host immunologic responses is associated to persistent HPV infection. The fact that effects were evident for all studied stimuli is suggestive of a generalized effect.
authors.affiliation: HPV Immunology Laboratory, Science Applications International Corporation-Frederick, Inc./National Cancer Institute-Frederick, Frederick, Maryland, USA.
authors.forename: Alfonso J
authors.initials: AJ
authors.lastname: García-Piñeres
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Matthew
authors.initials: M
authors.lastname: Trivett
authors.forename: Marcus
authors.initials: M
authors.lastname: Williams
authors.forename: Ivannia
authors.initials: I
authors.lastname: Atmetlla
authors.forename: Margarita
authors.initials: M
authors.lastname: Ramírez
authors.forename: Maricela
authors.initials: M
authors.lastname: Villegas
authors.forename: Mark
authors.initials: M
authors.lastname: Schiffman
authors.forename: Ana Cecilia
authors.initials: AC
authors.lastname: Rodríguez
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burk
authors.forename: Mariana
authors.initials: M
authors.lastname: Hildesheim
authors.forename: Enrique
authors.initials: E
authors.lastname: Freer
authors.forename: José
authors.initials: J
authors.lastname: Bonilla
authors.forename: Concepción
authors.initials: C
authors.lastname: Bratti
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
mesh_terms: D000367:Age Factors; D000368:Aged; D052685:Alphapapillomavirus / Q000235:genetics; D016022:Case-Control Studies; D015331:Cohort Studies; D003364:Costa Rica / Q000453:epidemiology; D004279:DNA, Viral / Q000302:isolation & purification; D005260:Female; D052140:Human papillomavirus 11; D006801:Humans; D008213:Lymphocyte Activation; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000453:epidemiology / Q000276:immunology*; D012725:Sexual Behavior
chemical_list: D004279:DNA, Viral