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ABSTRACT: Background. The purpose of this study was to examine the rate of and risks for cervical 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. Sera was obtained at baseline and annually.Results. 1,543 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 2(nd) 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 CIN 2/3 was rare in women with redetection except for those with a prevalent HPV16.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 since it appears that this small subset reflects women with persistence already present at entry.
The Journal of Infectious Diseases 04/2013; · 6.41 Impact Factor
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ABSTRACT: 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 non-genital anatomic sites. Transmission rates for femalegenital to male genital ranged from 26.8-187.5 per 100 person-months and for male genital to female genital from 14.5-100 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.
The Journal of Infectious Diseases 01/2013; · 6.41 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
The Journal of Infectious Diseases 06/2012; 206(4):504-11. · 6.41 Impact Factor
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ABSTRACT: Higher rates of human papillomavirus (HPV) in adolescents and younger women have been attributed to their greater extent of "cervical ectopy," defined as columnar and metaplastic epithelia on the ectocervix. Our objective was to estimate associations between ectopy and incident HPV in healthy adolescents and young women.
Enrolled between October 2000 and October 2002, this prospective cohort included women aged 13-21 years who were sexually active, without previous cervical intraepithelial neoplasia, cervical procedures, or immunosuppression, with menarche within 6 years before enrollment, and negative for HPV DNA at baseline. Every 4 months, extent of ectopy was quantitatively measured using colpophotography and computerized planimetry. Cox proportional hazards models examined associations between ectopy and incident HPV, defined as the first positive HPV result during follow-up.
The 138 women attended 509 total visits. At baseline, mean age was 16.7 years and mean extent of ectopy was 25% of the total cervical face. Incident HPV of any type was detected in 42 (30%) women and was not significantly associated with baseline ectopy (hazard ratio 1.09, 95% confidence interval 0.96-1.25; P=.20; ectopy in units of 10%), or with ectopy measured 4 months before HPV detection (hazard ratio 1.09, confidence interval 0.94-1.26; P=.25). Our sample size had 80% power to detect a hazard ratio of 1.9 (with two-tailed α=0.05). Results were similarly insignificant for HPV subgroupings of incident high-risk, low-risk, α9, and α3/α15 types, and when adjusted for new sexual partners.
Extent of cervical ectopy was not associated with HPV acquisition in healthy adolescents and young women. Biological vulnerabilities may lie in immune function or other characteristics of the cervical epithelium.
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Obstetrics and Gynecology 06/2012; 119(6):1164-70. · 4.73 Impact Factor
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ABSTRACT: We analyzed the effects of the Colorado Medicaid Capitation Program on the duration and services of over 21,000 outpatient mental health episodes for young children. The study spanned a three year period before and after capitation was implemented, and compared episodes of outpatient care for children from 14 capitated Community Mental Health Centers (CMHCs) with those from three CMHCs that remained fee-for-service. Proportional hazards regressions revealed that capitation resulted in an increase in outpatient episode duration, over and above similar effects for the comparison fee-for-service episodes. The hypothesis that there were longer capitated episodes for children who were hospitalized was not supported. Children with behavioral and anxiety disorders had longer capitated episodes. Service intensity decreased over time in the managed care sites. Changes in case mix may have had an impact on changes in episode duration and service intensity. That outpatient episode duration increased over time while costs were lowered in the capitated agencies indicates some effects of capitation in changing patterns of care.
Journal of Child and Family Studies 04/2012; 15(1):13-26. · 1.12 Impact Factor
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ABSTRACT: Misunderstanding of prescription labels results in adverse drug events and non-adherence. We assessed the effect of limited English and other factors on prescription understanding among five ethnic groups in a controlled analysis.
Subjects were respondents to California's 2007 Health Interview Survey who received a prescription in the past year. In separate logistic regressions, limited English's effect on self-reported prescription understanding - controlling for bilingual doctor, education level, medications for chronic conditions, disability, years in USA, citizenship and socio-demographics - was estimated for Mexicans, Central Americans, Chinese, Koreans, and Vietnamese.
Unweighted sample size was 48,968. Approximately 14% had limited English and 8% had difficulty in understanding prescriptions. In multivariate analysis, limited English increased odds of difficulty in understanding prescriptions by three times for Mexicans, Central Americans, and Koreans, and four times for Chinese; it was insignificant for Vietnamese. Generally, having a bilingual doctor reduced odds of difficulty while disability, low education, low income or recent immigration increased odds of difficulty. Effects varied according to the ethnic group. In controlled analysis, Chinese and Korean ethnicity increased odds of difficulty compared to Mexican or Central American ethnicity; Vietnamese ethnicity reduced odds of difficulty compared to others.
Limited English blocked prescription understanding for all groups except Vietnamese. Translated prescription labels and interpreted in-person pharmacy consultations are indicated. Education and ethnicity affected prescription understanding; prescription instructions must be compatible with patients' educational level and culture. Bilingual/bicultural providers and interpreters can help bridge linguistic/cultural gaps but efforts should be made to ensure that they are truly culturally and linguistically concordant. Linguistic, cultural or educational needs should be noted in the patient's record or on the prescription to alert pharmacy staff. Sub-populations needing extra support include chronically ill, disabled, recent immigrants, low-income or rural inhabitants. Community outreach workers may provide an effective strategy for assisting these sub-populations with prescriptions.
Ethnicity and Health 04/2011; 16(2):125-44. · 1.64 Impact Factor
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ABSTRACT: 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 after viral acquisition, in a cohort well characterized for HPV infections. Wilcoxon rank sum test was used to compare the change seen from preinfection 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 preincident 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.
International Journal of Cancer 02/2011; 128(4):879-86. · 5.44 Impact Factor
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ABSTRACT: To describe the natural history of cervical intraepithelial neoplasia (CIN) 2 in a prospective study of adolescents and young women, and to examine the behavioral and biologic factors associated with regression and progression.
Adolescents and women aged 13 to 24 years who were referred for abnormal cytology and were found to have CIN 2 on histology were evaluated at 4-month intervals. Risks for regression were defined as three consecutive negative cytology and histology visits, and progression to CIN 3 was estimated using Cox proportional hazards regression models.
Ninety-five patients with a mean age of 20.4 years (±2.3) were entered into the analysis. Thirty-eight percent resolved by year 1, 63% resolved by year 2, and 68% resolved by year 3. Multivariable analysis found that recent Neisseria gonorrhoeae infection (hazard ratio 25.27; 95% confidence interval [CI] 3.11-205.42) and medroxyprogesterone acetate use (per month) (hazard ratio 1.02; 95% CI 1.003-1.04) were associated with regression. Factors associated with nonregression included combined hormonal contraception use (per month) (hazard ratio 0.85; 95% CI 0.75-0.97) and persistence of human papillomavirus (HPV) of any type (hazard ratio 0.40; 95% CI 0.22-0.72). Fifteen percent of patients showed progression by year 3. HPV 16/18 persistence (hazard ratio 25.27; 95% CI 2.65-241.2; P=.005) and HPV 16/18 status at last visit (hazard ratio 7.25; 95% CI 1.07-49.36; P<.05) were associated with progression Because of the small sample size, other covariates were not examined.
The high regression rate of CIN 2 supports clinical observation of this lesion in adolescents and young women.
Obstetrics and Gynecology 12/2010; 116(6):1373-80. · 4.73 Impact Factor
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ABSTRACT: Young women aged 15-24 years have the highest rates of sexually transmitted infections (STIs). The vulnerability of adolescents is often attributed to risky sexual behaviors, whereas biological factors affecting mucosal immunity are poorly understood. The objective of this cross-sectional study was to examine associations between the type of cervical epithelium and protein levels of 11 cervicovaginal cytokines and chemokines in non-pregnant healthy young women. Cervical epithelial types were viewed on colpophotography and measured quantitatively using computerized planimetry. We selected 16 women with immature epithelium (predominantly columnar and early/mid squamous metaplasia), and 16 women with mature epithelium (predominantly squamous epithelium). Cytokine levels were measured in cervicovaginal lavage samples by MILLIPLEX™ MAP Human Cytokine/Chemokine multiplex immunoassay. Bivariate Box-Cox regression models compared cytokine levels between immature and mature groups. Multivariate Box-Cox models adjusted separately for age, years since menarche, days since last menses, years of sexual activity, number of lifetime sexual partners, HPV infection, hormonal contraceptive use, smoking, bacterial vaginosis by Nugent's criteria, and polymorphonuclear cells on wet prep. The mean age was 19.2 years. Women with immature epithelium demonstrated significantly higher levels of IL-1α, IL-1β, IL-6, IL-8, MIP-1α, RANTES, TNFα, IL-10, IL-12 and IFNγ (each p<0.01), compared to women with mature epithelium. Results remained highly significant in the multivariate models. Cytokine profiles in the healthy state may foreshadow differential responses to pathogens. Cervical epithelial type should be measured in clinical studies involving cervicovaginal immune markers.
Journal of Reproductive Immunology 11/2010; 88(1):66-71. · 2.97 Impact Factor
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Anna-Barbara Moscicki,
Lea Widdice, Yifei Ma,
Sepideh Farhat,
Susanna Miller-Benningfield,
Janet Jonte,
Julie Jay,
Cheryl Godwin de Medina,
Evelyn Hanson,
Lisa Clayton,
Stephen Shiboski
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ABSTRACT: New strategies for cervical cancer screening include human papillomavirus (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 4 low-risk (LR) 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.
International Journal of Cancer 10/2010; 127(8):1882-92. · 5.44 Impact Factor
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ABSTRACT: To determine whether 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 United States.
A cross-sectional study nested in a phase 1 microbicide trial.
Cervical cytobrushes were collected from 18 to 24-year-old women in San Francisco, California, USA (n = 18) and Kisumu, Kenya (n = 36) at enrollment into a phase 1 microbicide trial. All participants tested negative for HIV, herpes simplex virus 2, gonorrhea, chlamydia, and trichomonas, and had abstained from sex for at least 7 days prior to enrollment. Cryopreserved T-cell populations were assayed by flow cytometry in a central laboratory. Secretory leukocyte protease inhibitor 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 participants from 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 C-C chemokine receptor type 5, and a greater proportion of activated CD8(+) T cells. Median (interquartile range) genital levels of secretory leukocyte protease inhibitor were lower in participants from Kisumu compared with those from San Francisco [190 (96-519) vs. 474 (206 817) pg/ml, P < 0.03].
Activated mucosal T cells were increased in the genital tract of young, sexually transmitted infection/HIV-free Kenyan women, independent of common genital coinfections, and secretory leukocyte protease inhibitor 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.
AIDS (London, England) 08/2010; 24(13):2069-74. · 4.91 Impact Factor
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ABSTRACT: Although human papillomavirus (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 ages 12 to 22 years were eligible. Interviews on behaviors and HPV testing were done at 4-month intervals; sexually transmitted infection (STI) testing was annual or if symptomatic. Starting with first HPV detection, time to the next (second) visit (event) with detection of new HPV types, and then the second event to time to third event was calculated. Risks were determined using Cox proportional hazard model.
Sixty-nine percent of 1,125 women had a second event, and of those with a second event, 63% had a third event by 3 years, respectively. Women with HPV persistence from initial visit to second event [hazard ratio (HR) = 4.51 (3.78-5.37)], an STI [HR = 1.47 (1.00-2.17)], bacterial vaginosis [HR = 1.60 (1.07-2.39)], and number of new sex partners [HR = 1.10 (1.05-1.15 per partner/mo)] were independent associations for HPV. Risks for third 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.
Cancer Epidemiology Biomarkers & Prevention 08/2010; 19(8):2055-65. · 4.12 Impact Factor
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ABSTRACT: Few studies have examined the relationships between sexual or hygienic behaviors and human papillomavirus (HPV) transmission. Our objectives were to (1) describe HPV concordance between the anogenital, oral, and palmar areas of monogamous heterosexual couples; and (2) determine sexual behaviors, hygienic practices, sexual histories, and subject characteristics associated with HPV anogenital concordance.
Couples were recruited from women who developed an incident HPV infection while being enrolled in a longitudinal HPV natural history study that recruited from two family-planning clinics. Men were their monogamous partners of at least 3 months. Samples were tested for HPV-DNA of 37 high- and low-risk genotypes. Questionnaires completed privately assessed health, sexual, hygienic history, and behaviors.
A total of 25 couples enrolled between February 2006 and July 2007; none had received HPV vaccine. The average age was 25 years (SD, 6) for men and 23 years (SD, 3) for women. HPV-84 was the most commonly shared HPV type in the anogenital and palmar areas. HPV-16 was the only shared oral-HPV type. Sixty-eight percent of couples had type-specific anogenital concordance. Receiving finger-anal sex (p = .05), sharing towels (p = .04), longer time since last intercourse (women: p = .03, men: p = .02 men), and men washing their genitals after sex (p = .03) were associated with decreased likelihood of concordance. Persistence of incident HPV types in women was associated with HPV in men (p = .002).
Our findings show that certain hygienic and sexual behaviors are associated with anogenital concordance between healthy, monogamous, heterosexual couples. Future studies are needed to see whether these detections reflect contamination, transient, or established infections.
Journal of Adolescent Health 08/2010; 47(2):151-9. · 3.33 Impact Factor
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Karen K Smith-McCune,
Stephen Shiboski,
Mike Z Chirenje,
Tsitsi Magure,
Jennifer Tuveson, Yifei Ma,
Maria Da Costa,
Anna-Barbara Moscicki,
Joel M Palefsky,
Rudo Makunike-Mutasa,
Tsungai Chipato,
Ariane van der Straten,
George F Sawaya
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ABSTRACT: Sexually transmitted infections (STIs) such as herpes simplex virus (HSV)-2 are associated with an increased risk of HIV infection. Human papillomavirus (HPV) is a common STI, but little is know about its role in HIV transmission. The objective of this study was to determine whether cervico-vaginal HPV infection increases the risk of HIV acquisition in women independent of other common STIs.
This prospective cohort study followed 2040 HIV-negative Zimbabwean women (average age 27 years, range 18-49 years) for a median of 21 months. Participants were tested quarterly for 29 HPV types (with L1 PCR primers) and HIV (antibody testing on blood samples with DNA or RNA PCR confirmation). HIV incidence was 2.7 per 100 woman-years. Baseline HPV prevalence was 24.5%, and the most prevalent HPV types were 58 (5.0%), 16 (4.7%), 70 (2.4%), and 18 (2.3%). In separate regression models adjusting for baseline variables (including age, high risk partner, positive test for STIs, positive HSV-2 serology and condom use), HIV acquisition was associated with having baseline prevalent infection with HPV 58 (aHR 2.13; 95% CI 1.09-4.15) or HPV 70 (aHR 2.68; 95% CI 1.08-6.66). In separate regression models adjusting for both baseline variables and time-dependent variables (including HSV-2 status, incident STIs, new sexual partner and condom use), HIV acquisition was associated with concurrent infection with any non-oncogenic HPV type (aHR 1.70; 95% CI 1.02-2.85), any oncogenic HPV type (aHR 1.96; 95% CI 1.16-3.30), HPV 31 (aHR 4.25; 95% CI 1.81-9.97) or HPV 70 (aHR 3.30; 95% CI 1.50-7.20). Detection of any oncogenic HPV type within the previous 6 months was an independent predictor of HIV acquisition, regardless of whether HPV status at the HIV acquisition visit was included (aHR 1.95; 95% CI 1.19-3.21) or excluded (aHR 1.96; 95% CI 1.02-2.85) from the analysis.
Cervico-vaginal HPV infection was associated with an increased risk of HIV acquisition in women, and specific HPV types were implicated in this association. The observational nature of our study precludes establishment of causation between HPV infection and HIV acquisition. However, given the high prevalence of HPV infection in women, further investigation of the role of HPV in HIV transmission is warranted.
PLoS ONE 01/2010; 5(4):e10094. · 4.09 Impact Factor
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ABSTRACT: To examine the longitudinal changes in the epithelial topography of the cervix in healthy young women; and to determine the sociodemographic, behavioral, and biological factors associated with the rate of cervical epithelial maturation.
Healthy young women were enrolled from October 2000 to September 2002 as part of a larger study of human papillomavirus (HPV). At interval visits, interviews, infection testing, and colpophotography (3% acetic acid; 10x, 16x magnifications) were performed. Areas of total cervical face and cervical immaturity, defined as columnar and early squamous metaplasia, were quantitatively measured using computerized planimetry. Cervical immaturity was expressed as percentage of total cervical face. This analysis includes the first consecutive 145 women with greater than 10% immaturity at baseline. The rate of cervical maturation was defined as change in percent-immaturity. Predictors included sociodemographics, sexual behaviors, and infections. Data analyses included multivariate generalized linear models with repeated measures.
The baseline mean age was 17.8 years. Colpophotographs were available from 815 total visits, representing 2.7 years mean follow-up per woman and 5.9-month mean intervals. Women began the study with a median of 39% immaturity and ended with 8% immaturity. After adjusting for time and baseline percent-immaturity, an increased rate of cervical maturation was associated with oral contraceptive pill use (parameter estimate -.023, p =.04) and smoking (-.039, p =.01).
Cervical maturation was documented during relatively short time periods for the vast majority of these women. Oral contraceptive pills and smoking may accelerate the maturational process, representing increased cell proliferation and thus a possible greater vulnerability to HPV.
Journal of Adolescent Health 03/2009; 44(2):103-10. · 3.33 Impact Factor
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ABSTRACT: To estimate the risks of cervical intraepithelial neoplasia (CIN) 3 among girls and women aged 13 to 24 years who were referred for abnormal cytology while receiving care in a large health maintenance organization.
At the time of referral, patients had a colposcopic examination and biopsy if needed. Histology was sent to a centralized laboratory. Patients were interviewed for risk behaviors. Data analysis included multinomial logistic regression analysis to compare three groups: CIN 3 to CIN 1 or less, CIN 3 to CIN 2, and CIN 2 to CIN 1 or benign.
Cervical intraepithelial neoplasia-3 was found in 6.6% (95% confidence interval [CI] 4.6-8.6%) of the 622 girls and women referred and no cancers were detected. Risk for CIN 3 compared to CIN 1 or less included human papillomavirus 16 or 18 (odds ratio [OR] 30.93, 95% CI 6.95-137.65), high-risk, non-16/18 human papillomavirus (OR 6.3, 95% CI 1.3-29.4), and time on oral contraceptives (OR 1.36 per year of use, 95% CI 1.08-1.71).
Our data support conservative care for adolescents and young women with abnormal cytology since CIN 3 was rare and cervical cancer was never found. Human papillomavirus 16 or 18 was strongly associated with for CIN 3, and testing for these types may be warranted for triage of abnormal cytology in this age group.
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Obstetrics and Gynecology 01/2009; 112(6):1335-42. · 4.73 Impact Factor
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George F Sawaya,
Mike Zvavahera Chirenje,
Mildred Tsitsi Magure,
Jennifer L Tuveson, Yifei Ma,
Stephen C Shiboski,
Maria M Da Costa,
Joel M Palefsky,
Anna-Barbara Moscicki,
Rudo Makunike Mutasa,
Tsungai Chipato,
Karen K Smith-McCune
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ABSTRACT: To estimate the effect of providing women with a latex diaphragm, lubricant gel, and male condoms (intervention) compared with condoms alone (control) on human papillomavirus (HPV) incidence and clearance.
Participants were 2,040 human immunodeficiency virus (HIV)-negative Zimbabwean women enrolled in a randomized trial estimating the effect of the intervention on HIV acquisition. Clinicians collected cervical samples for HPV testing at baseline, 12 months, and exit. L1 consensus polymerase chain reaction primers were used to determine HPV presence and type.
We found no differences in the following outcomes: HPV prevalence at the time of the first postenrollment HPV test (intention-to-treat analysis, relative risk [RR] 1.02, 95% confidence interval [CI] 0.90-1.16); HPV incidence at 12 months among women HPV-negative at baseline (RR 0.95, 95% CI 0.80-1.14); and HPV clearance at 12 months among women HPV-positive at baseline (RR 0.80, 95% CI 0.61-1.05). Clearance of HPV type 58 was lower in the intervention group at 12 months (RR 0.67, 95% CI 0.48-0.92), but not at exit (RR 0.93, 95% CI 0.75-1.16); clearance of HPV type 18 was lower in the intervention group at exit (RR 0.55, 95% CI 0.33-0.89), but not at 12 months (RR 0.55, 95% CI 0.29-1.05). Women reporting diaphragm/gel use at 100% of prior sex acts had a lower likelihood of having one or more new HPV types detected at 12 months (RR 0.75, 95% CI 0.58-0.96) and exit (RR 0.77, 95% CI 0.59-0.99).
Among women receiving risk reduction counseling and condoms in an HIV prevention program, diaphragm plus lubricant gel provision did not affect HPV incidence or clearance.
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00211459
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Obstetrics and Gynecology 12/2008; 112(5):990-7. · 4.73 Impact Factor
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ABSTRACT: Cervical mucosal expression of cytokines involved in mediating cellular immunity is believed to influence the persistence of human papillomavirus (HPV) infection, a necessary prerequisite for the development of cervical intraepithelial neoplasia (CIN). Additionally, regulatory T (Treg) cells are increasingly understood to be important modulators of cellular immunity. Using quantitative RT-PCR, we measured, in cross-sectional design, the cervical mRNA expression of IFN-gamma, IL-10, and IL-12, as well as the Treg transcription factor Forkhead box P3 (Foxp3), in a cohort of young women representing CIN 1, 2, and 3, as well as benign histology. Higher levels of IFN-gamma and IL-10 were significantly (p <or= 0.05) associated with decreased odds of having high-grade cervical disease (CIN 2 or 3) in multivariate logistic regression models. In contrast, higher levels of mucosal Foxp3 expression were associated with increased odds of having CIN 2 or 3 (p = 0.004). In a multivariate model including cervical infection with HPV16 and/or another high-risk HPV type, Foxp3 remained higher in the CIN 2/3 group, but the difference was notably less significant (p = 0.05). These findings support a model in which diminished cellular immunity in the cervical mucosa and mucosal enrichment of Treg cells both contribute to the development of high-grade lesions.
International Journal of Cancer 10/2008; 124(6):1379-83. · 5.44 Impact Factor
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ABSTRACT: Cytokines in cervical mucus are likely to play important roles in controlling pathogens. The cervical mucosal environment is complex, however, with many endogenous and exogenous factors that may affect cytokine levels. We used a multiplex, suspension-array-based immunoassay method to measure 10 proinflammatory (interleukin-1beta [IL-1beta], IL-6, and IL-8) and immunoregulatory (gamma interferon [IFN-gamma], IL-2, IL-4, IL-5, IL-10, IL-12, and IL-13) cytokines in cervical mucus specimens collected via ophthalmic sponge from 72 healthy, nonpregnant women and correlate their levels with biologic and behavioral covariates in a cross-sectional design. Proinflammatory and immunoregulatory cytokines were readily detected, although proinflammatory cytokines were present at markedly higher levels than were immunoregulatory cytokines. Among the covariates examined, the most striking finding was the significant (P < or = 0.05) association between depressed levels of the cytokines IFN-gamma, IL-1beta, IL-6, and IL-10 and cigarette smoking. Also, nonsignificant trends toward lower cytokine levels were found in the settings of incident and persistent human papillomavirus infection. The ready detection of proinflammatory cytokines may be reflective of the female genital tract as an anatomic site that is constantly exposed to immunogenic stimulation. Cigarette smoking appears to downregulate cytokine responses in the cervical mucosa, which may help explain the implicated role of tobacco use as a cofactor for cervical cancer development.
Clinical and vaccine immunology: CVI 01/2008; 15(1):49-54. · 2.37 Impact Factor
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ABSTRACT: Measurements of mucosal immune parameters in the uterine cervix are potentially influenced by numerous factors, including infections, endogenous and exogenous hormones, semen, and nicotine and its metabolites in cervical mucus. The objective of this study was to examine correlates of immunoregulatory cytokine mRNA expression in cervical cytology samples in a cross-sectional design. Samples, collected at study entry by cervical cytology brush from 368 women aged 13-21 enrolled in a longitudinal study of the natural history of human papillomavirus (HPV) infection, were tested by quantitative RT-PCR for expression of IFN-gamma, IL-4, IL-10, and IL-12. In a multivariate analysis, elevated levels of IFN-gamma, IL-10, and IL-12 were significantly (p < 0.05) associated with several variables, including current C. trachomatis infection, recent intercourse, and current oral contraceptive pill use. Suppressed IL-4 and IL-10 levels were associated with cigarette smoking within the last 24 h. Time since last menstrual period did not affect any of the cytokines; in a substudy of weekly cytokine variability, however, IL-10 showed a non-significant trend toward higher levels around the time of menstruation.
Journal of Clinical Immunology 05/2006; 26(3):222-32. · 3.08 Impact Factor
