Anal human papillomavirus (HPV) 16 infections were more likely to persist than other high-risk HPV types, and sexual behaviors were strongly associated with its persistence. As HPV-16 is responsible for 90% of anal cancers, prevention should include education around sexual practices.
Background. Anal cancer is more common in women than in men, yet little is known about the natural history of human papillomavirus (HPV) in women. The objective was to examine the natural history of anal HPV in heterosexual women.
Methods. Young women participating in an HPV cohort study were seen at 4-month intervals for cervical and anal HPV testing. Time to clearance was estimated using the Kaplan-Meier approach; risks for persistence were assessed using Cox regression models.
Results. Seventy-five women (mean age, 23.5 ± 4.1 years) who tested positive for anal HPV were followed for a mean of 84.5 ± 44.9 months. By 3 years, 82.5% of anal non-16 high-risk (HR) HPV, 82.6% of low-risk (LR) HPV, and 76.2% of HPV-16 infections had cleared. By 3 years, only 36.4% of women had become negative for all HPV types. In the multivariable model, concurrent cervical HPV-16 (P < .001), weekly alcohol use (P = .015), anal touching during sex (P = .045), recent anal sex (P = .04), and no condom use during anal sex (P = .04) were associated with HPV-16 persistence. Greater number of new sex partners (P = .024) and condom use during vaginal sex (P = .003) were associated with clearance. Similar associations were found for clearance in all HR-HPV infections. Only concomitant cervical HPV was associated with non-16 HR-HPV persistence.
Conclusions. The majority of anal HPV infections cleared within 3 years. HPV-16 infections were slower to clear than other HR-HPV infections, consistent with its role in anal cancer. Specific sexual behaviors were associated with persistence, suggesting that education and behavioral interventions may decrease persistence.
anal; human papillomavirus infection; persistence; women
Despite advances in treatment of people living with HIV, morbidity and mortality remains unacceptably high in sub-Saharan Africa, largely due to parallel epidemics of poverty and food insecurity.
We conducted a pilot cluster randomized controlled trial (RCT) of a multisectoral agricultural and microfinance intervention (entitled Shamba Maisha) designed to improve food security, household wealth, HIV clinical outcomes and women’s empowerment. The intervention was carried out at two HIV clinics in Kenya, one randomized to the intervention arm and one to the control arm. HIV-infected patients >18 years, on antiretroviral therapy, with moderate/severe food insecurity and/or body mass index (BMI) <18.5, and access to land and surface water were eligible for enrollment. The intervention included: 1) a microfinance loan (~$150) to purchase the farming commodities, 2) a micro-irrigation pump, seeds, and fertilizer, and 3) trainings in sustainable agricultural practices and financial literacy. Enrollment of 140 participants took four months, and the screening-to-enrollment ratio was similar between arms. We followed participants for 12 months and conducted structured questionnaires. We also conducted a process evaluation with participants and stakeholders 3–5 months after study start and at study end.
Baseline results revealed that participants at the two sites were similar in age, gender and marital status. A greater proportion of participants at the intervention site had a low BMI in comparison to participants at the control site (18% vs. 7%, p = 0.054). While median CD4 count was similar between arms, a greater proportion of participants enrolled at the intervention arm had a detectable HIV viral load compared with control participants (49% vs. 28%, respectively, p < 0.010). Process evaluation findings suggested that Shamba Maisha had high acceptability in recruitment, delivered strong agricultural and financial training, and led to labor saving due to use of the water pump. Implementation challenges included participant concerns about repaying loans, agricultural challenges due to weather patterns, and a challenging partnership with the microfinance institution. We expect the results from this pilot study to provide useful data on the impacts of livelihood interventions and will help in the design of a definitive cluster RCT.
This trial is registered at ClinicalTrials.gov, NCT01548599.
Electronic supplementary material
The online version of this article (doi:10.1186/s40064-015-0886-x) contains supplementary material, which is available to authorized users.
HIV; Food insecurity; Microfinance; Agriculture; Livelihoods; Intervention
Background. The purpose of this study was to examine the rate of and risks for cervical human papillomavirus type 16 (HPV16) redetection in women with documented or suspected HPV16 infection.
Methods. A convenience sample of women aged 13–21 years were seen at 4-month intervals for HPV DNA testing and cytology. Serum samples were obtained at baseline and annually.
Results. A total of 1543 women entered the study. Of the 295 women with detection of HPV16 DNA and subsequent clearance, 18.1% had HPV16 redetected by 8.5 years (88% cleared this second detection by 3 years). Of the 247 women who had antibodies to HPV16 and were HPV16 DNA negative at baseline, 15.3% had HPV16 redetected by year 5. Risks for redetection included douching, current use of medroxyprogesterone, reporting >1 sex partner or having a new sex partner, and having a sexually transmitted infection. Development of cervical intraepithelial neoplasia 2/3 was rare in women with redetection, except for those with prevalent HPV16 infection.
Conclusions. Reappearance of HPV16 DNA was observed in 18% of women. Most are associated with sexual exposure and appear benign. Interpretation of the studies is more complex in women with prevalent infections as it appears that this small subset reflects women with persistence already present at entry.
redetection of HPV16; reactivation; risk for acquisition; risk for clearance
Serum microRNAs hold great promise as easily accessible and measurable biomarkers of disease. In prostate cancer, serum miRNA signatures have been associated with the presence of disease as well as correlated with previously validated risk models. However, it is unclear whether miRNAs can provide independent prognostic information beyond current risk models. Here, we focus on a group of low-risk prostate cancer patients who were eligible for active surveillance, but chose surgery. A major criteria for the low risk category is a Gleason score of 6 or lower based on pre-surgical biopsy. However, a third of these patients are upgraded to Gleason 7 on post surgical pathological analysis. Both in a discovery and a validation cohort, we find that pre-surgical serum levels of miR-19, miR-345 and miR-519c-5p can help identify these patients independent of their pre-surgical age, PSA, stage, and percent biopsy involvement. A combination of the three miRNAs increased the area under a receiver operator characteristics curve from 0.77 to 0.94 (p<0.01). Also, when combined with the CAPRA risk model the miRNA signature significantly enhanced prediction of patients with Gleason 7 disease. In-situ hybridizations of matching tumors showed miR-19 upregulation in transformed versus normal-appearing tumor epithelial, but independent of tumor grade suggesting an alternative source for the increase in serum miR-19a/b levels or the release of pre-existing intracellular miR-19a/b upon progression. Together, these data show that serum miRNAs can predict relatively small steps in tumor progression improving the capacity to predict disease risk and, therefore, potentially drive clinical decisions in prostate cancer patients. It will be important to validate these findings in a larger multi-institutional study as well as with independent methodologies.
Background. Because many human papillomavirus (HPV) infections are transient, rates of transmission may be miscalculated if the interval between testing spans several months. We examined rates of concordance and transmission in heterosexual couples over short intervals.
Methods. Twenty-five adult couples were enrolled and sampled for HPV DNA from the genitals, hand, and mouth 5 times over a 6-week period, including 24 hours after sexual intercourse and after 48 hours of abstinence. Concordance and transmission patterns were described.
Results. Concordance between the couple's genital sites ranged from 64% to 95% for at least 1 HPV type. The highest rates of concordance were observed 24 hours after sexual intercourse. A similar peak in concordance was not seen between genital and nongenital anatomic sites. Transmission rates for female genital to male genital ranged from 26.8 to 187.5 per 100 person-months and for male genital to female genital from 14.5 to 100 per 100 person-months.
Conclusions. High rates of concordance shortly after intercourse suggest that some DNA detections in the genital area are contaminants from a partner and not established HPV infections. Female-to-male transmission appeared more common than male-to-female transmission.
heterosexual transmission; HPV
In the US, the peak hepatitis C (HCV) antibody prevalence of 4% occurred in persons born in calendar years 1940 to 1965.
To examine observed and projected age-specific trends in the demand for liver transplantation (LTx) among patients with HCV-associated liver disease stratified by concurrent hepatocellular carcinoma (HCC).
All new adult LTx candidates registered with the Organ Procurement and Transplantation Network for LTx between 1995 and 2010 were identified. Patients who had primary, secondary, or text field diagnoses of HCV with or without HCC, were identified.
There were 126,862 new, primary registrants for LTx, 52,540 (41%) with HCV. The number of new registrants with HCV was dramatically different by age at calendar year, suggesting a birth cohort effect. When stratified by birth year in 5-year intervals, the birth cohorts with the highest frequency of HCV in decreasing order were those born 1951-1955, 1956-1960, 1946-1950, and 1941-1945. These four birth cohorts, spanning 1941 to 1960 accounted for 81% of all new registrants with HCV. A 4-fold increase in new registrants with HCV and HCC occurred between calendar years 2000 to 2010 in the 1941-1960 birth cohorts. By 2015, we anticipate an increasing proportion of new registrants with HCV will have HCC and be over the age of 60 (born on or before 1955).
The greatest demand for LTx due to HCV-associated liver disease is occurring among individuals born between 1941 and 1960. This demand appears to be driven by the development of HCC in patients with HCV. Over the coming decade, the projected increase in demand for LTx from an aging HCV infected population will challenge the transplant community to reconsider current treatment paradigms.
Hepatitis C; Hepatocellular carcinoma; liver transplantation
papillomavirus infections; HIV; meta-analysis; human papillomavirus; risk factors
Background. Vulnerability of younger women to human papillomavirus 16 (HPV16) infection has been attributed to the predominance of ectocervical columnar epithelia in this age group. However, squamous metaplastic tissue may be more influential. We examined the extent of ectopy and metaplastic activity as risks for HPV16 acquisition in a prospective cohort.
Methods. Participants were HPV16 negative at the first two visits. Follow-up occurred every 4 months. Ectopy was quantitatively measured on colpophotographs. We calculated metaplastic rate as the difference in ectopy between visits. Cox proportional hazards models were constructed, adjusting for several covariates.
Results. Analyses included 198 women (mean baseline age 17 years) for 1734 visits. Mean follow-up was 4.4 years. Incident HPV16 was detected in 36 (18%) women. Metaplastic rate between the two visits before HPV16 detection was significantly associated with incident infection (hazard ratio [HR], 1.17; confidence interval [CI], 1.02–1.33; P = .02). However, ectopy was not significant, whether measured before or concurrent to HPV16 detection (HR range, 0.99–1.00; CI range, .97–1.02; P range, .47–.65).
Conclusions. Dynamic metaplasia rather than the sheer extent of ectopy appears to increase risk for incident HPV16 in healthy young women. This in vivo observation is consistent with the HPV life cycle, during which host cell replication and differentiation supports viral replication.
To study the prevalence of extra-glandular manifestations (EGM) in primary Sjögren’s Syndrome (pSS) among participants enrolled in the Sjögren’s International Collaborative Clinical Alliance (SICCA) registry.
1927 participants in the SICCA registry were studied, including 886 participants who met the 2002 American-European consensus group (AECG) criteria for pSS, 830 “intermediate” cases who had some objective findings of pSS but did not meet AECG criteria, and 211 control individuals. We studied the prevalence of immunologic and hematologic laboratory abnormalities; specific rheumatologic examination findings; and physician confirmed thyroid, liver, kidney disease and lymphoma among SICCA participants.
Laboratory abnormalities, including hematologic abnormalities, hypergammaglobulinemia and hypocomplementemia, frequently occurred among pSS cases, and were more common among the intermediate cases than among control participants. Cutaneous vasculitis and lymphadenopathy were also more common among pSS cases. In contrast, the frequency of physician confirmed diagnoses of thyroid, liver and kidney disease, and lymphoma was low and only primary biliary cirrhosis was associated with pSS cases status. Rheumatologic and neurologic symptoms were common among all SICCA participants, regardless of case status.
Data from the international SICCA registry support the systemic nature of pSS, manifest primarily in terms of specific immunologic and hematologic abnormalities. The occurrence of other systemic disorders among this cohort is relatively uncommon. Previously reported associations may be more specific to select patient subgroups, such as those referred for evaluation of certain neurologic, rheumatologic or other systemic manifestations.
Alcohol is heavily consumed in sub-Saharan Africa and affects HIV transmission and treatment but is difficult to measure. Our goal was to examine the test characteristics of a direct metabolite of alcohol consumption, phosphatidylethanol (PEth).
Persons infected with HIV were recruited from a large HIV clinic in southwestern Uganda. We conducted surveys and breath alcohol concentration (BRAC) testing at 21 daily home or drinking establishment visits and blood was collected on day 21 (n=77). PEth in whole blood was compared to prior 7-, 14-, and 21-day alcohol consumption.
1) The receiver operator characteristic area under the curve (ROC-AUC) was highest for PEth versus any consumption over the prior 21 days (0.92; 95% CI: 0.86-0.97). The sensitivity for any detectable PEth was 88.0% (95% CI: 76.0-95.6%) and the specificity was 88.5% (95% CI: 69.8-97.6%). 2) The ROC-AUC of PEth versus any 21-day alcohol consumption did not vary by age, body mass index, CD4 cell count, hepatitis B virus infection and antiretroviral therapy status, but was higher for men compared to women (p=0.03). 3) PEth measurements were correlated with several measures of alcohol consumption, including number of drinking days in the prior 21 (Spearman r=0.74, p<0.001) and BRAC (r=0.75, p<0.001).
The data add support to the body of evidence for PEth as a useful marker of alcohol consumption with high ROC-AUC, sensitivity, and specificity. Future studies should further address the period and level of alcohol consumption for which PEth is detectable.
Alcohol; biomarker; phosphatidylethanol; HIV; Africa
As gene expression profile (GEP) testing for breast cancer may provide additional prognostic information to guide the use of adjuvant chemotherapy, we examined the association between GEP testing and use of chemotherapy, serious chemotherapy-related adverse effects, and total charges during the 12 months following diagnosis.
Medical record review was conducted for women age 30 to 64 years, with incident, non-metastatic, invasive breast cancer diagnosed 2006–2008 in a large, national health plan.
Of 534 patients, 25.8% received GEP testing, 68.2% received chemotherapy, and 10.5% experienced a serious chemotherapy-related adverse effect. GEP testing was most commonly used in women at moderate clinical risk of recurrence (52.0% vs. 25.0% of low-risk women and 5.5% of high-risk). Controlling for the propensity to receive GEP testing, women who had GEP were less likely to receive chemotherapy (propensity adjusted odds ratio, 95% confidence interval 0.62, 0.39 – 0.99). Use of GEP was associated with more chemotherapy use among women at low risk based on clinical characteristics (OR = 42.19; CI 2.50 – 711.82), but less use among women with a high risk based on clinical characteristics (OR = 0.12 CI 0.03 – 0.47). Use of GEP was not associated with chemotherapy for the moderate risk group. There was no significant relationship between GEP use and either serious chemotherapy-associated adverse effects or total charges.
While GEP testing was associated with an overall decrease in adjuvant chemotherapy, we did not find differences in serious chemotherapy-associated adverse events or charges during the 12 months following diagnosis.
breast cancer; utilization; genomics
The aim of this study was to examine the effect of the 3% SPL 7013 gel (VivaGel®) on mucosal immune markers hypothesized to be associated with HIV-1 acquisition.
Phase 1, placebo-controlled, randomized, double-blind clinical trial was performed in 54 young women in the U.S. and Kenya. Participants used carbopol gel with and without (placebo) SPL 7013 twice daily over 14 days. Cervical specimens were collected for cytokines, chemokines, T-cells, and dendritic cells at day (D) 0, 7, 14, and 21. A negative binomial regression model was used to assess differences between study arms.
Several mucosal immune parameters were increased in the VivaGel® arm compared to placebo. For cytokines: D 7, IL-6 (p=0.05); D 14, IFN-γ (p=0.03), IL-2 (p=0.04), IL-5 (p=0.003) and IL-10 (p=0.001) were increased. On D 7, CD8+/CD69+ T-cells tended to be increased (p<0.08); limiting analysis to visits without blood or bacterial vaginosis, these findings were stronger: at D7, CD8+/CD69+ T-cells were increased in the VivaGel® arm (p<0.005), as were CD4+/CD69+ cells (p=0.001) and CD4+/CCR5+ T-cells (p=0.01). The changes described for D7 and 14 were no longer seen at D21.
Markers associated with inflammation and epithelial damage were reversibly elevated in the VivaGel® arm compared to the placebo arm after 7–14 days of twice daily product use.
Vaginal microbicide; mucosal immune markers
Several fastidious bacteria have been associated with bacterial vaginosis (BV), but their role in lactobacilli recolonization failure is unknown. We studied the effect of seven BV-associated bacterial species and two Lactobacillus species on vaginal colonization with L. crispatus CTV-05 (LACTIN-V).
Twenty four women with BV were given a 5-day course of metronidazole vaginal gel and then randomized 3:1 to receive either LACTIN-V or placebo applied vaginally once daily for 5 initial consecutive days, followed by a weekly application over 2 weeks. Vaginal swabs for L. crispatus CTV-05 culture and 9-bacterium specific 16S rRNA gene quantitative PCR assays were analyzed on several study visits for the 18 women receiving LACTIN-V.
Vaginal colonization with CTV-05 was achieved in 61% of the participants receiving LACTIN-V at either the day 10 or the 28 visit and 44% at day 28. Participants not colonized with CTV-05 had generally higher median concentrations of BV-associated bacteria compared to those who colonized. Between enrollment and day 28, the median concentration of Gardnerella vaginalis minimally reduced from 104.5 to 104.3 16S rRNA gene copies per swab in women who colonized with CTV-05 but increased from 105.7 to 107.3 in those who failed to colonize (p=0.19). Similarly, the median concentration of Atopobium spp. reduced from 102.7 16S rRNA gene copies per swab to below limit of detection in women who colonized with CTV-05 but increased from 102.7 to 106.6 in those who failed to colonize (p=0.04). The presence of endogenous L. crispatus at enrollment was found to be significantly associated with a reduced odds of colonization with CTV-05 on day 28 (p=0.003) and vaginal intercourse during the study significantly impaired successful CTV-05 colonization (p=0.018).
Vaginal concentration of certain BV-associated bacteria, vaginal intercourse during treatment and presence of endogenous L. crispatus at enrollment predict colonization with probiotic lactobacilli.
Bacterial vaginosis; BV-associated bacteria; Lactobacillus probiotics; Lactobacillus crispatus CTV-05
Background. Bacterial vaginosis (BV) has been linked to female HIV acquisition and transmission. We investigated the effect of providing a latex diaphragm with Replens and condoms compared to condom only on BV prevalence among participants enrolled in an HIV prevention trial. Methods. We enrolled HIV-seronegative women and obtained a vaginal swab for diagnosis of BV using Nugent's criteria; women with BV (score 7–10) were compared to those with intermediate (score 4–6) and normal flora (score 0–3). During quarterly follow-up visits over 12–24 months a vaginal Gram stain was obtained. The primary outcome was serial point prevalence of BV during followup. Results. 528 participants were enrolled; 213 (40%) had BV at enrollment. Overall, BV prevalence declined after enrollment in women with BV at baseline (OR = 0.4, 95% CI 0.29–.56) but did not differ by intervention group. In the intention-to-treat analysis BV prevalence did not differ between the intervention and control groups for women who had BV (OR = 1.01, 95% CI 0.52–1.94) or for those who did not have BV (OR = 1.21, 95% CI 0.65–2.27) at enrollment. Only 2.1% of participants were treated for symptomatic BV and few women (5–16%) were reported using anything else but water to cleanse the vagina over the course of the trial. Conclusions. Provision of the diaphragm, Replens, and condoms did not change the risk of BV in comparison to the provision of condoms alone.
The mechanisms involved in mucosal immune control of cervical human papillomavirus (HPV) infection remain ill-defined. Because Toll-like receptors (TLRs) are key players in innate immune responses, we investigated the association between TLR expression and viral persistence or clearance in young women with incident infections with oncogenic HPV types 16 or 51. Messenger RNA expression of TLR1, TLR2, TLR3, TLR4, TLR6, TLR7, TLR8, and TLR9 was measured by quantitative reverse transcription-PCR using human endocervical specimens, collected before and following viral acquisition, in a cohort well characterized for HPV infections. Wilcoxon rank sum test was used to compare the change seen from pre-infection to incident infection between women who subsequently cleared infection with those who did not. HPV 16 infections that cleared were significantly (P < 0.05) associated with an increase in expression of the four viral nucleic acid-sensing TLRs (TLR3, TLR7, TLR8 and TLR9) as well as TLR2 upon viral acquisition. Similar associations were not observed for HPV 51. In women who subsequently cleared their HPV 16 infection, changes in TLR1, TLR3, TLR7, and TLR8 expression levels between pre-incident and incident visits were significantly correlated with parallel changes in the levels of interferon-α2, measured by immunoassay in cervical lavage specimens. This study suggests that dampened TLR expression in the cervical mucosa is a type-specific mechanism by which HPV 16 interferes with innate immune responses, contributing to viral persistence, and that TLR upregulation and resultant cytokine induction is important in subsequent viral clearance.
toll-like receptors; human papillomavirus; persistence
Latent class analysis allows the estimation of test sensitivities and specificities in the absence of a gold standard. PCR outperformed clinical examination and intense trachomatous inflammation (TI) appeared much more specific than follicular trachomatous inflammation (TF).
Tests for ocular Chlamydia trachomatis have not been well characterized, because there is no gold standard test. Latent class analysis (LCA) was performed to estimate the sensitivity and specificity of laboratory and clinical tests for trachoma in the absence of a gold standard.
Individual data from pretreatment, hyperendemic areas in Ethiopia were used. A clustered LCA was performed for three diagnostic tests: PCR and WHO simplified criteria grades of follicular trachoma (TF) and intense trachomatous inflammation (TI).
Data from 2111 subjects in 40 villages were available. TF was estimated to be 87.3% (95% CI, 83.3–90.1) sensitive and 36.6% (95% CI, 23.6–40.3) specific; TI was estimated to be 53.6% (95% CI, 46.1–88.0) sensitive and 88.3% (95% CI, 83.3–92.0) specific, and PCR was estimated to be 87.5% (95% CI, 79.9–97.2) sensitive and 100% (95% CI 69.3–100) specific.
LCA allows for an estimate of test characteristics without prior assumption of their performance. TF and TI were found to act in a complementary manner: TF is a sensitive test and TI is a specific test. PCR is highly specific but lacks sensitivity. The performance of these tests may be due to the time course of ocular chlamydial infection, and for this reason, results may differ in areas of low prevalence or recent mass treatment (ClinicalTrials.gov number, NCT00221364).
Fetal microchimerism (F-MC), the persistence of fetal cells in the mother, is frequently encountered following pregnancy. The high prevalence of F-MC in autoimmune disease prompts consideration of the role for immune tolerance and regulation. This study examines the association between F-MC and multiple sclerosis (MS), an autoimmune disorder, of undetermined etiology.
21 out of 51 MS-positive subjects (41%) were classified as positive for F-MC; 4 of 22 (18%) of MS-negative sibling controls, were also positive for MC (p = 0.066). Unanticipated F-MC in controls lead to re-evaluation using 30 female singleton cord blood units (CBUs) as a biological control. Four CBUs were low-level positive.
Study Design and Methods:
Seventy-three female subjects were assigned to three groups according to disease status and pregnancy history: (1) MS positive (+) women with a history of one male pregnancy before symptom onset (n = 27); (2) MS negative (−) female siblings of MS+ women with a history of one male pregnancy (n = 22); and (3) MS+ women that reported never having been pregnant (n = 24). Ten micrograms of genomic DNA obtained from peripheral blood leukocytes of each subject were analyzed for F-MC using allele-specific real-time PCR targeting the SR-Y sequence on the Y-chromosome. MC classification was dichotomous (positive vs. negative) based on PCR results.
The association between F-MC and MS warrants further study to define this relationship. F-MC in women self-reporting as nulligravid, supports previous findings that a significant proportion of pregnancies go undetected. This lead to re-validation of a Y-chromosome based assay for F-MC detection.
multiple sclerosis; microchimerism; fetal cells; autoimmune disease; twinning; pregnancy
Objective. Cervical human papillomavirus (HPV) infection has been associated with human immunodeficiency virus (HIV) acquisition in populations with a high prevalence of both infections. Procedures performed in the management of cervical dysplasia may facilitate HIV entry via mechanical injury. We sought to investigate the association between cervical procedures and incident HIV. Methods. Data on cervical cancer screening and procedures were collected in a cohort study evaluating the diaphragm for HIV prevention in 2040 women. In this secondary analysis, we investigated the association between cervical procedures and HIV acquisition. Results. Out of 2027 HIV-negative women at baseline, 199 underwent cervical procedures. Cumulative risk of HIV was 4.3% over 21 months of median followup (n = 88). Compared with women without cervical procedures, we observed no difference in HIV incidence after a cervical biopsy (RR 0.92, 95% CI 0.39–2.16), endocervical curettage (RR 0.29, 95% CI 0.07–1.22), or loop electrosurgical excision procedure (RR 1.00, 95% CI 0.30–3.30). Conclusions. In this cohort, cervical procedures were not associated with HIV incidence. This lack of association could be due to the small number of events.
New strategies for cervical cancer screening include HPV DNA testing. Using self-testing methods would increase access to testing in both developed and developing countries. The purpose of this study was to compare time-to-clearance of specific HPV types between clinician-collected-lavage (CC-L) and self-collected (SC) sampling in a single cohort. CC-L and SC samples were obtained every 4 months at alternate 2-month windows from 537 women. Eighteen high-risk (HR) HPV and 4low-risk HPV were examined. Proportional hazards model was used to compare time-to-clearance between methods for combined HR and for 13 specific HPV types. Prentice-Wilcoxon test was used for within-subject paired comparison. In the independent analysis for combined HR and LR types, no differences were found. For specific types, time-to-clearance for all HPV types examined between CC-L and SC samples was similar except for HPV 66 which showed a trend to clear slower by SC (p=0.09). When comparing methods in the same woman, time-to-clearance was similar for all types except for HPV 16 which showed a trend to clear slower by CC-L means (p=0.08). When we examined pattern of clearance among the CC-L samples, the fastest types to clear were HPV 6, 18, 66, 84 and 39 and the slowest were HPV 62, 68, 59 and 16. These patterns of fast and slow were similar for SC samples. Our findings suggest using SC vaginal swabs would observe similar natural histories of HPV compared to studies using CC-L specimens making self-testing feasible for repeated HPV DNA detection.
HPV natural history; self-sampling; clinician-sampling
To determine if healthy, young women in sub-Saharan Africa have a more activated immune milieu in the genital tract (i.e. activated CD4+ T-cells) than a similar population in the US.
Cross-sectional study nested in a phase 1 microbicide trial.
Cervical cytobrushes were collected from 18–24 year old women in San Francisco, CA (n=18) and Kisumu, Kenya (n=36) at enrollment into a phase 1 microbicide trial. All participants tested negative for HIV, HSV-2, gonorrhea, chlamydia and trichomonas, and had abstained from sex for at least seven days prior to enrollment. Cryopreserved T-cell populations were assayed by flow cytometry in a central laboratory. SLPI levels were assayed in cervicovaginal lavage samples. The Wilcoxon rank-sum test was used to compare immune parameters between sites.
The total number of endocervical CD4+ T-cells was slightly higher in San Francisco, but participants from Kisumu had a substantially higher number and proportion of CD4+ T-cells expressing the early activation marker CD69, with and without the HIV-coreceptor CCR5, and a greater proportion of activated CD8+ T-cells. Median [interquartile] genital levels of SLPI were lower in participants from Kisumu compared to those from San Francisco (190 pg/mL [96, 519] vs. 474 pg/mL [206, 817]; p<0.03).
Activated mucosal T-cells were increased in the genital tract of young, STI/HIV-free Kenyan women, independent of common genital co-infections, and SLPI levels were reduced. The cause of these mucosal immune differences is not known, but could partly explain the high HIV incidence in young women from sub-Saharan Africa.
HIV transmission; mucosal immunology; female genital tract; sub-Saharan Africa; CD4+ T-cells; SLPI
Although HPV infections are common in young women, the rate of and risk for repeated new infections are not well documented. We examined the rate of and risks for new HPV detection in young women.
We used data from an ongoing study of HPV, initiated in 1990. Sexually active women aged 12–22 years were eligible. Interviews on behaviors and HPV testing were performed at 4-month intervals; sexually transmitted infection (STI) testing was annual or if symptomatic. Starting with 1st HPV detection, time to the next (2nd) visit (event) with detection of new HPV types and then the 2nd event to time to 3rd event was calculated. Risks were determined using Cox Proportional hazard model.
Sixty-nine percent of 1,125 women had a 2nd event and of those with a 2nd event, 63% had a 3rd event by 3 years, respectively. Women with HPV persistence from initial visit to 2nd event [Hazard ratio (H.R.) = 4.51 (3.78 – 5.37)], an STI (H.R. = 1.47 (1.00 – 2.17), bacterial vaginosis (H.R. = 1.60 (1.07 – 2.39), and number of new sex partners (H.R. = 1.10 (1.05 – 1.15 per partner/month) were independent associations for HPV. Risks for 3rd event were similar.
This study documents the repeated nature of HPV infections in young women and their association with sexual risk behaviors.
This finding underscores the lack of clinical utility of HPV testing in young women. Further studies are needed to examine host factors that lead to HPV acquisition and persistence.
HPV infections; adolescents; risk behavior; sexually transmitted infections
To describe the natural history of CIN-2 in a prospective study of young women and to examine the behavioral and biologic factors associated with regression and progression.
Women aged 13 to 24 years referred for abnormal cytology and were found to have CIN-2 on histology were followed at 4-month intervals. Risks for regression defined as 3 consecutive negative cytology and histology visits and progression to CIN-3 were estimated using Cox proportional hazards regression models.
Ninety-five women with a mean age of 20.4 years (± 2.3) were entered into the analysis. Thirty-eight percent cleared by year 1, 63% by year 2 and 68% by year 3. Multivariable analysis found that recent N. gonorrhoeae infection (H.R. = 25.27 [95% C.I. 3.11, 205.42]) and medroxyprogesterone acetate use (per month) (H.R. = 1.02 [95% C.I. 1.003, 1.04]) were associated with regression. Factors associated with non-regression included combined hormonal contraception use (per month) (H.R. = 0.85 [95% C.I. 0.75, 0.97]) and persistence of HPV of any type (H.R. = 0.40 [95% C.I. 0.22, 0.72]). Fifteen percent of women showed progression by year 3. HPV 16/18 persistence (H.R. = 25.27 [95% C.I.2.65, 241.2, p = 0.005]) and HPV 16/18 status at last visit (H.R. = 7.25 [95% C.I. 1.07, 49.36); p < 0.05]) was associated with progression Because of the small sample size, other co-variates were not examined.
The high regression rate of CIN-2 supports clinical observation of this lesion in young women.
Latino children are at increased risk for mirconutrient deficiencies and problems of overweight and obesity. Exposures in pregnancy and early postpartum may impact future growth trajectories.
To evaluate the relationship between prenatal and postnatal maternal depressive symptoms experienced in pregnancy and infant growth from birth to 2 years of age in a cohort of Latino infants.
We recruited pregnant Latina mothers at two San Francisco hospitals and followed their healthy infants to 24 months of age. At 6, 12 and 24 months of age, infants were weighed and measured. Maternal depressive symptoms were assessed prenatally and at 4-6 weeks postpartum. Women who had high depressive symptoms at both time periods were defined as having chronic depression. Logistic mixed models were applied to compare growth curves and risk for overweight and underweight based on exposure to maternal depression.
We followed 181 infants to 24 months. At 12 and 24 months, respectively, 27.4% and 40.5% were overweight, and 5.6% and 2.2% were underweight. Exposure to chronic maternal depression was associated with underweight (OR = 12.12, 95%CI 1.86-78.78) and with reduced weight gain in the first 2 years of life (Coef = -0.48, 95% CI -0.94—0.01) compared with unexposed infants or infants exposed to episodic depression (depression at one time point). Exposure to chronic depression was also associated with reduced risk for overweight in the first 2 years of life (OR 0.28, 95%CI 0.03-0.92).
Exposure to chronic maternal depression in the pre- and postnatal period was associated with reduced weight gain in the first two years of life and greater risk for failure to thrive, in comparison with unexposed infants or those exposed episodically. The infants of mothers with chronic depression may need additional nutritional monitoring and intervention.
To assess the safety of VivaGel® used vaginally twice daily for 14 days among healthy, sexually-abstinent women, aged 18–24 years in the USA and Kenya.
Randomized placebo controlled trial.
Participants were randomized 2∶1, VivaGel to placebo. Safety was assessed by comparing genitourinary (GU) adverse events (AEs), colposcopy findings, vaginal lactobacilli and laboratory abnormalities by arm.
Fifty-four women were enrolled; 35 in the VivaGel arm and 19 in the placebo arm. Twenty-six (74%) and 10 (53%) women reported taking all doses of VivaGel and placebo, respectively. No grade 3 or 4 AEs, or serious AEs occurred. Twenty-five (71%) participants in the VivaGel arm compared to 10 (53%) participants in the placebo arm had at least one grade 1 or 2 GU AE associated with product use (RR = 1.4, 95% CI 0.8-2.2). All seven grade 2 GU AEs associated with product use occurred among four women in the VivaGel arm. Vulvar and cervical erythema, cervical lesions, symptomatic BV, urinary frequency and metrorrhagia were more common in the VivaGel arm than the placebo arm. Twenty-nine (83%) participants in the VivaGel arm had a colposcopic finding compared to 10 (53%) participants in the placebo arm (RR = 1.6, 95%CI = 1.0-2.5). Two women in the VivaGel arm prematurely discontinued product use themselves due to a reported GU AE. Persistence of H2O2-producing and non-producing lactobacilli did not differ by study arm.
GU AEs and colposcopic findings consistent with mild epithelial irritation and inflammation occurred more commonly among women in the VivaGel arm.