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 (z65 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.

Mulheres Portadoras de lesões Precursoras do câncer do colo do Útero e hPV: descrição do Perfil socioeconôMico e deMográfico

“…Os tipos virais HPV 16 e 18 estão mais associados a lesões de alto grau e a persistência da infecção pelo HPV, por períodos maiores de 6 meses em mulheres mais velhas 18 . Isto se deve ao fato de que a persistência da infecção por papilomavírus humano está associada a uma queda generalizada de resposta imunológica em mulheres mais velhas 23 . Vale destacar que a duração da infecção é maior para o HPV de alto risco oncogênico do que para os de baixo risco 24 .…”

A review of prophylactic human papillomavirus vaccines: Recommendations and monitoring in the US

“…Factors such as smoking, older age, HPV type, duration of infection, and suppressed immunity have been identified as predictors of persistent infections. 3,[34][35][36] A recent study of persistent infection in a cohort in Costa Rica produced no evidence of interactions between detection of multiple HPV types and the incidence of new infection or persistent infection, implying that HPV types act independently. 36 Despite the extensive studies evaluating the natural history of HPV infection, the dynamics of acquisition, clearance and immune response to infection, and transmission are incompletely understood.…”

Host and viral factors in relation to clearance of human papillomavirus infection: A cohort study in Taiwan

“…Several host factors such as older age, 8 hormone replacement therapy, 12 concurrent other lower genital tract infections, 13 generalized decrease in immune responsiveness, 14 parous women 15 ; and viral variables such as HPV genotype, 8,15,16 multiple HPV infections, 8,13 HPV variants 17 have been reported associated with HPV persistence/decreased clearance, whereas ever users of oral contraceptives were associated with faster clearance. 15 Multiple infections, viral load 15 and smoking 8 were unrelated to clearance in other longitudinal follow-up studies.…”