Primary HPV and Molecular Cervical Cancer Screening in US Women Living With Human Immunodeficiency Virus.

Background: Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomavirus (oncHPV) testing as the initial cervical cancer screening method and typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH).

Methods: We enrolled n = 865 WLWH (323 from the Women's Interagency HIV Study [WIHS] and 542 from WIHS-affiliated colposcopy clinics).

Natural History of Cervical Intraepithelial Neoplasia-2 in HIV-Positive Women of Reproductive Age.

Objective: To evaluate the natural history of treated and untreated cervical intraepithelial neoplasia-2 (CIN2) among HIV-positive women.

Methods: Participants were women enrolled in the Women's Interagency HIV Study between 1994 and 2013. One hundred four HIV-positive women diagnosed with CIN2 before age 46 were selected, contributing 2076 visits over a median of 10 years (interquartile range 5-16).

Methylation of High-Risk Human Papillomavirus Genomes Are Associated with Cervical Precancer in HIV-Positive Women.

Background: HIV-positive women are at substantial risk of HPV-associated cervical neoplasia caused by high-risk (HR) HPVs. Methylation of the HPV genome is associated with cervical intraepithelial neoplasia grade 3 (CIN3) in HIV-negative women, yet it is unknown whether this holds true for HIV-positive women.

Methods: We designed a case-control study within the Women's Interagency HIV Study (WIHS) cohort comparing HIV-positive CIN3 cases ( = 72) to HIV-positive controls without detectable CIN2.

Racial differences in human papilloma virus types amongst United States women with HIV and cervical precancer.

Objective: Recent studies reported a lower human papillomavirus 16 (HPV16) prevalence in cervical precancer among African American than Caucasian women in the general population. We assessed this relationship in women with HIV.

Design: Women living with or at risk for HIV in the Women's Interagency HIV Study were followed semi-annually with Pap tests, colposcopy/histology (if indicated), and collection of cervicovaginal lavage samples for HPV testing by PCR.

Prolonged Amenorrhea and Resumption of Menses in Women with HIV.

Objective: To compare etiologies of prolonged amenorrhea in a cohort of HIV-infected women with a cohort of similar uninfected at-risk women.

Materials And Methods: Women from the Women's Interagency HIV Study were seen every 6 months, and completed surveys including questions about their menstruation. Those who reported no vaginal bleeding for at least 1 year ("prolonged amenorrhea") with subsequent resumption of bleeding were compared with women in whom bleeding had stopped permanently ("menopause").

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.

Cervical cancer screening intervals and management for women living with HIV: a risk benchmarking approach.

Objective: We suggested cervical cancer screening strategies for women living with HIV (WLHIV) by comparing their precancer risks to general population women, and then compared our suggestions with current Centers for Disease Control and Prevention (CDC) guidelines.

Design: We compared risks of biopsy-confirmed cervical high-grade squamous intraepithelial neoplasia or worse (bHSIL+), calculated among WLHIV in the Women's Interagency HIV Study, to 'risk benchmarks' for specific management strategies in the general population.

Methods: We applied parametric survival models among 2423 WLHIV with negative or atypical squamous cell of undetermined significance (ASC-US) cytology during 2000-2015.

Correlates of Bacterial Vaginosis Over Long-Term Follow-Up: Impact of HIV Infection.

Correlates of bacterial vaginosis (BV) are poorly understood, especially in HIV infection. In a cohort study, HIV-seropositive and comparison seronegative women were assessed every 6 months during 1994-2015. BV was considered present when three of four Amsel criteria were met.

Multitype Infections With Human Papillomavirus: Impact of Human Immunodeficiency Virus Coinfection.

Background: Human 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.

Methods: Human immunodeficiency virus-seropositive women and -seronegative comparison women were enrolled in a cohort study and followed every 6 months from 1994 to 2006.

The Cervicovaginal Microbiota and Its Associations With Human Papillomavirus Detection in HIV-Infected and HIV-Uninfected Women.

Background:  Bacterial vaginosis (BV) is characterized by low abundance of Lactobacillus species, high pH, and immune cell infiltration and has been associated with an increased risk of human papillomavirus (HPV) infection. We molecularly assessed the cervicovaginal microbiota over time in human immunodeficiency virus (HIV)-infected and HIV-uninfected women to more comprehensively study the HPV-microbiota relationship, controlling for immune status.

Methods:  16S ribosomal RNA gene amplicon pyrosequencing and HPV DNA testing were conducted annually in serial cervicovaginal lavage specimens obtained over 8-10 years from African American women from Chicago, of whom 22 were HIV uninfected, 22 were HIV infected with a stable CD4 T-cell count of > 500 cells/mm, and 20 were HIV infected with progressive immunosuppression.

Longitudinal Assessment of Systemic and Genital Tract Inflammatory Markers and Endogenous Genital Tract E. coli Inhibitory Activity in HIV-Infected and Uninfected Women.

Problem: Stability over time of systemic and mucosal immunity and their associations with bacterial vaginosis (BV) and HIV-specific parameters were assessed.

Method Of Study: Immune mediators and HIV viral load in plasma and cervicovaginal lavage (CVL), E. coli inhibition, and Nugent score were measured at three semiannual visits among 94 participants in the Women's Interagency HIV Study.

The Effects of Viral Load Burden on Pregnancy Loss among HIV-Infected Women in the United States.

Background: To evaluate the effects of HIV viral load, measured cross-sectionally and cumulatively, on the risk of miscarriage or stillbirth (pregnancy loss) among HIV-infected women enrolled in the Women's Interagency HIV Study between 1994 and 2013.

Methods: We assessed three exposures: most recent viral load measure before the pregnancy ended, log10 copy-years viremia from initiation of antiretroviral therapy (ART) to conception, and log10 copy-years viremia in the two years before conception.

Results: The risk of pregnancy loss for those with log10 viral load >4.

Association of cervical precancer with human papillomavirus types other than 16 among HIV co-infected women.

Background: HIV-seropositive women face high risk for infection with oncogenic human papillomavirus (oncHPV) types, abnormal Pap test results, and precancer, but cervical cancer risk is only modestly increased. Human papillomavirus (HPV)16 is highly oncogenic but only weakly associated with HIV status and immunosuppression, suggesting HPV16 may have a greater innate ability to evade host immune surveillance than other oncHPV types, which in turn should result in a greater relative increase in the prevalence of other oncHPV types among women with cervical precancer.

Objective: We sought to assess whether the underrepresentation of HPV16 among HIV-seropositive relative to HIV-seronegative women remains among those with cervical precancers.

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.

Methods: A total of 2791 HIV-infected and 975 HIV-uninfected women in the Women's Interagency HIV Study were followed semiannually with Pap tests and colposcopy. Cumulative risks of cervical intraepithelial neoplasia grade 2 or greater (CIN-2+; threshold used for CIN treatment) and grade 3 or greater (CIN-3+; threshold to set screening practices) were measured in HIV-infected and HIV-uninfected women with normal Pap tests, stratified by baseline HPV results, and also in HIV-infected women with a low-grade squamous intraepithelial lesion (LSIL; benchmark indication for colposcopy).

Changes in knowledge of cervical cancer following introduction of human papillomavirus vaccine among women at high risk for cervical cancer.

Purpose: To describe changes in knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination among women at high risk for cervical cancer in the first five years after introduction of HPV vaccination.

Methods: In 2007, 2008-9, and 2011, women in a multicenter U.S.

Incidence of cervical precancers among HIV-seropositive women.

Objective: The objective of the study was to estimate the impact of human immunodeficiency virus (HIV) infection on the incidence of high-grade cervical intraepithelial neoplasia (CIN).

Study Design: HIV-seropositive and comparison seronegative women enrolled in a prospective US cohort study were followed up with semiannual Papanicolaou testing, with colposcopy for any abnormality. Histology results were retrieved to identify CIN3+ (CIN3, adenocarcinoma in situ, and cancer) and CIN2+ (CIN2 and CIN3+).

Genital tract HIV RNA levels and their associations with human papillomavirus infection and risk of cervical precancer.

Objective: Plasma HIV RNA levels have been associated with the risk of human papillomavirus (HPV) and cervical neoplasia in HIV-seropositive women. However, little is known regarding local genital tract HIV RNA levels and their relation with cervical HPV and neoplasia.

Design/methods: In an HIV-seropositive women's cohort with semiannual follow-up, we conducted a nested case-control study of genital tract HIV RNA levels and their relation with incident high-grade squamous intraepithelial lesions (HSIL) subclassified as severe (severe HSIL), as provided for under the Bethesda 2001 classification system.

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.

Long-term cumulative incidence of cervical intraepithelial neoplasia grade 3 or worse after abnormal cytology: impact of HIV infection.

To estimate the long term cumulative risk for cervical intraepithelial neoplasia grade 3 or worse after an abnormal cervical Pap test and to assess the effect of HIV infection on that risk. Participants in the Women's Interagency HIV Study were followed semiannually for up to 10 years. Pap tests were categorized according to the 1991 Bethesda system.

Abnormal pap tests and human papillomavirus infections among HIV-infected and uninfected women who have sex with women.

Objective: To estimate the frequency of abnormal Pap and human papillomavirus (HPV) positivity among human immunodeficiency virus (HIV)-seropositive and -seronegative women who have sex with women (WSW).

Methods: Pap and HPV DNA polymerase chain reaction tests were obtained every 6 months from women in a US cohort of HIV-seropositive and -seronegative women. Women who have sex with women were women reporting no male and at least 1 female sex partner for 5 years.

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.

Plasma and mucosal HIV viral loads are associated with genital tract inflammation in HIV-infected women.

Background: Systemic and mucosal inflammation may play a role in HIV control. A cross-sectional comparison was conducted among women in the Women's Interagency HIV Study to explore the hypothesis that compared with HIV-uninfected participants, women with HIV, and, in particular, those with high plasma viral load (PVL) have increased levels of mucosal and systemic inflammatory mediators and impaired mucosal endogenous antimicrobial activity.

Methods: Nineteen HIV-uninfected, 40 HIV-infected on antiretroviral therapy (ART) with PVL ≤ 2600 copies/mL (low viral load) (HIV-LVL), and 19 HIV-infected on or off ART with PVL >10,000 (high viral load) (HIV-HVL) were evaluated.

Negative predictive value of pap testing: implications for screening intervals for women with human immunodeficiency virus.

Objective: To estimate the accuracy of Pap testing for women who are human immunodeficiency virus (HIV)-seropositive, with a focus on negative predictive value.

Methods: Participants 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.

Risk of cervical precancer and cancer among HIV-infected women with normal cervical cytology and no evidence of oncogenic HPV infection.

Context: US cervical cancer screening guidelines for human immunodeficiency virus (HIV)-uninfected women 30 years or older have recently been revised, increasing the suggested interval between Papanicolaou (Pap) tests from 3 years to 5 years among those with normal cervical cytology (Pap test) results who test negative for oncogenic human papillomavirus (HPV). Whether a 3-year or 5-year screening interval could be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown.

Objective: To determine the risk of cervical precancer or cancer defined cytologically (high-grade squamous intraepithelial lesions or greater [HSIL+]) or histologically (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), as 2 separate end points, in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test result and were negative for oncogenic HPV.