The relation of plasmacytoid dendritic cells (pDCs) and regulatory t-cells (Tregs) with HPV persistence in HIV-Infected and HIV-Uninfected women

Other than CD4+ count, the immunologic factors that underlie the relationship of HIV/AIDS with persistent oncogenic HPV (oncHPV) and cervical cancer are not well understood. Plasmacytoid dendritic cells (pDCs) and regulatory T-cells (Tregs) are of particular interest. pDCs have both effector and antigen presenting activity and, in HIV-positive patients, low pDC levels are associated with opportunistic infections. Tregs downregulate immune responses, and are present at high levels in HIV-positives. The current pilot study shows for the first time that low pDC and high Treg levels may be significantly associated with oncHPV persistence in both HIV-positive and HIV-negative women. Larger studies are now warranted

Cervical Precancer Risk in HIV-Infected Women Who Test Positive for Oncogenic Human Papillomavirus Despite a Normal Pap Test

Background. Determining cervical precancer risk among human immunodeficiency virus (HIV)–infected women who despite a normal Pap test are positive for oncogenic human papillomavirus (oncHPV) types is important for setting screening practices

The Use of TSH in Determining Thyroid Disease: How Does It Impact the Practice of Medicine in Pregnancy?

During the last four decades, there have been considerable advances in the efficacy and precision of serum thyroid function testing. The development of the third generation assays for the measurement of serum thyroid stimulating hormone (TSH, thyrotropin) and the log-linear relationship with free thyroxine (T4) established TSH as the hallmark of thyroid function testing. While it is widely accepted that TSH outside of the normal range is consistent with thyroid dysfunction, a vast multitude of additional factors must be considered before an accurate clinical diagnosis can be made. This is especially important during pregnancy, when the thyroid is under considerable additional pregnancy-related demands requiring significant maternal physiological changes. This paper examines serum TSH measurement in pregnancy and some associated potential confounding factors

Multitype Infections With Human Papillomavirus

BackgroundHuman immunodeficiency virus (HIV) infection predisposes women to genital coinfection with human papillomaviruses (HPVs). Concurrent infection with multiple HPV types has been documented, but its frequency, correlates, and impact on development of precancer are poorly defined in HIV-seropositive women.MethodsHuman immunodeficiency virus-seropositive women and -seronegative comparison women were enrolled in a cohort study and followed every 6 months from 1994 to 2006. Cervicovaginal lavage samples were tested for HPV types using polymerase chain reaction amplification with MY09/MY11 consensus primers followed by hybridization with consensus and HPV type-specific probes. Analyses were performed using generalized estimating equations.ResultsMultitype HPV infections were found in 594 (23%) of 2543 HIV-seropositive women and 49 (5%) of 895 HIV-seronegative women (P < 0.0001). Compared with HPV uninfected women, those with multiple concurrent HPV infections were more likely to be younger, nonwhite, and current smokers, with lower CD4 counts and HIV RNA levels. The average proportion of women with multitype HPV infections across visits was 21% in HIV-seropositive women and 3% in HIV-seronegative women (P <0.0001). Compared with infection with 1 oncogenic HPV type, multitype concurrent infection with at least 1 other HPV type at baseline did not measurably increase the risk of ever having cervical intraepithelial neoplasia 3+ detected during follow-up (odds ratio, 0.80; 95% confidence interval, 0.32-2.03, P = 0.65).ConclusionsConcurrent multitype HPV infection is common in HIV-seropositive women and frequency rises as CD4 count declines, but multitype infection does not increase precancer risk

Negative Predictive Value of Pap Testing

ObjectiveTo estimate the accuracy of Pap testing for women who are human immunodeficiency virus (HIV)-seropositive, with a focus on negative predictive value.MethodsParticipants in the Women's Interagency HIV Study were monitored with conventional Pap tests every 6 months. After excluding those with abnormal Pap test results before study, cervical disease, or hysterectomy, women with negative enrollment Pap test results were monitored for development of precancer within 15 or 39 months, defined as a Pap test result read as high-grade squamous intraepithelial lesion, atypical glandular cells favor neoplasia, or adenocarcinoma in situ, or a cervical biopsy read as cervical intraepithelial neoplasia 2 or worse. Correlations between one or more consecutive negative Pap test results and subsequent precancer were assessed using Cox proportional hazards models.ResultsAmong 942 HIV-infected women with negative baseline Pap test results, eight (1%) developed precancer within 15 months and 40 (4%) within 39 months. After three consecutive negative Pap test results, precancer was rare, with no cases within 15 months and 10 of 539 (2%) within 39 months. No women developed precancer or cancer within 39 months after 10 consecutive negative Pap test results. Risks for precancer within 15 months after negative Pap test result included current smoking (adjusted hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.2-2.0 compared with nonsmokers), younger age (adjusted HR 1.5, 95% CI 1.1-2.1 for women aged younger than 31 years compared with older than 45 years), and lower CD4 count (adjusted HR 11.8, 95% CI 1.3-2.3 for CD4 200-500/microliter, adjusted HR 2.2, 95% CI 1.6-2.9 for CD4 less than 200/microliter, compared with CD4 more than 500/microliter).ConclusionAnnual Pap testing appears safe for women infected with HIV; for those with serial negative tests, longer intervals are appropriate.Level of evidenceII

Cervical cancer incidence after up to 20 years of observation among women with HIV.

To estimate the incidence of invasive cervical cancer (ICC) across up to 21 years of follow-up among women with human immunodeficiency virus (HIV) and to compare it to that among HIV-uninfected women, we reviewed ICC diagnoses from a 20-year multi-site U.S. cohort study of HIV infected and uninfected women who had Pap testing every 6 months. Incidence rates were calculated and compared to those in HIV-negative women. Incidence ratios standardized to age-, sex-, race-, and calendar-year specific population rates were calculated. After a median follow-up of 12.3 years, four ICCs were confirmed in HIV seropositive women, only one in the last 10 years of observation, and none in seronegative women. The ICC incidence rate did not differ significantly by HIV status (HIV seronegative: 0/100,000 person-years vs. HIV seropositive: 19.5/100,000 person-years; p = 0.53). The standardized incidence ratio for the HIV-infected WIHS participants was 3.31 (95% CI: 0.90, 8.47; p = 0.07). Although marginally more common in women without HIV, for those with HIV in a prevention program, ICC does not emerge as a major threat as women age