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Biomedical subjects

Teresa M Darragh

Publications and source records attributed to Teresa M Darragh.

At least 19 recordsLinked to original sources
PubMed2006

A trial of SGN-00101 (HspE7) to treat high-grade anal intraepithelial neoplasia in HIV-positive individuals.

OBJECTIVES: To test a therapeutic vaccine consisting of a fusion of the human papillomavirus (HPV) 16 E7 protein and the Mycobacterium bovis heat shock protein 65 (SGN-00101) to treat high-grade anal intraepithelial neoplasia (HG-AIN) in HIV-positive individuals. DESIGN: A phase I/II trial with three cohorts of five participants each, sequentially assigned to receive 100, 500 or 1000 microg SGN-00101, injected three times subcutaneously in alternating thighs at 4-week intervals. Anal disease was assessed at baseline, 8, 12, 24 and 48 weeks and was classified as the more severe of anal cytology and anal biopsy. Anal HPV DNA was detected using L1 consensus primer-based PCR followed by type-specific probing and dot-blot hybridization (DBH). HPV16, 18 and 31 DNA copy numbers were measured using quantitative real-time PCR. SETTING: University-based research clinic. PARTICIPANTS: Thirteen HIV-positive men and two HIV-positive women with HG-AIN. RESULTS: There were no drug-related serious adverse events or significant changes in HIV viral load and CD4/CD8 ratio. At 48 weeks, two of five participants in both the 100 and 500 microg cohorts regressed to AIN 1 and one of five participants in the 1000 microg cohort regressed to atypical squamous cells of undetermined significance (ASC-US). All participants had at least one oncogenic HPV type at baseline. Three of five (60%) participants who regressed to AIN 1 or ASC-US became HPV-negative using DBH and real-time PCR, compared with none of 10 participants with no clinical response (P = 0.02). CONCLUSIONS: SGN-00101 was well tolerated in HIV-positive individuals, with preliminary evidence for clinical activity.

Adult↗
PubMed2006

Effect of Replens gel used with a diaphragm on tests for human papillomavirus and other lower genital tract infections.

OBJECTIVE: Little is known about effects of vaginal lubricants with barrier contraceptives on detection of sexually transmissible infections. We hypothesized that Replens gel used with a diaphragm would neither inhibit human papillomavirus (HPV) detection in cervical samples and chlamydia (CT) and gonorrhea (GC) detection in urine samples, nor affect cervical cytology quality. MATERIALS AND METHODS: After a clinician-collected cervical sample and a self-collected vaginal sample for HPV detection ("pregel" specimens), women placed a diaphragm containing Replens gel into the vagina. Participants (n = 77) removed the diaphragm after 6 hours and performed vaginal HPV self-sampling at several time points thereafter. Clinicians performed cervical cytology sampling and HPV testing ("postgel" specimens) 24 hours after diaphragm removal. Pregel and postgel specimens were analyzed with and without added SiHa cells (source of defined numbers of HPV16 genomes). HPV was detected by polymerase chain reaction using MY09/11 primers. Urine samples were obtained for CT and GC testing. Proportions of samples testing positive were compared using relative risk (RR) regression models. RESULTS: Proportions with detectable HPV in the clinician-collected cervical pregel and postgel samples were not statistically different for samples with added SiHa cells (88.3% vs 93.2%, RR = 1.06, 95% confidence interval = 0.96-1.14) or for native HPV infection (32.9% vs 28.2%, RR = 0.87, 95% confidence interval = 0.71-1.06). In self-collected vaginal postgel samples, there was no trend for decreased HPV detection after gel exposure. Gel affected neither urine tests for CT and GC nor cytological quality. CONCLUSIONS: Recent Replens gel use with a diaphragm does not inhibit cervical HPV testing, urine testing for CT and GC, or cervical cytology quality.

Adolescent↗
PubMed2005

Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men.

OBJECTIVES: The incidence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of highly active antiretroviral therapy (HAART). The prevalence of the putative anal cancer precursor, anal intraepithelial neoplasia (AIN) was high among HIV-positive MSM prior to the availability of HAART but little is known about AIN since HAART was introduced. We characterized the prevalence of AIN among HIV-positive MSM and examined the association between AIN and various factors including use of HAART. DESIGN AND METHODS: A baseline point-prevalence analyses in a prospective cohort study of AIN was performed at a university-based research clinic. A total of 357 HIV-positive MSM with no history of anal cancer completed a questionnaire detailing behaviors and medical history, anal cytology and human papillomavirus (HPV) testing, and high-resolution anoscopy with biopsy for detection of AIN. RESULTS: Eighty-one percent of participants with available CD4+ cell counts at baseline had AIN of any grade; 52% had AIN 2 or 3; and 95% had anal HPV infection. In multivariate analysis, detection of > or = 6 HPV types [odds ratio (OR), 36; 95% confidence interval (CI), 7.4-171) and use of HAART (OR, 10; 95% CI, 2.6-38) were associated with AIN after adjustment for length of time participants were HIV-positive, CD4+ cell count and HIV viral load. CONCLUSIONS: The prevalence of AIN has remained high among HIV-positive MSM after the introduction of HAART. Our data indicate that HAART is not associated with a reduced prevalence of AIN and support measures to prevent anal cancer among HIV-positive MSM whether or not they are using HAART.

AIDS-Related Opportunistic Infections↗
PubMed2005

Home study course: summer 2005.

OBJECTIVE: The Home Study Course is intended for the practicing colposcopist or practitioner who is seeking to develop or enhance his or her colposcopic skills. The goal of the course is to present colposcopic cases that are unusual or instructive in terms of appearance, presentation, or management, or that demonstrate new and important knowledge in the area of colposcopy or pathology. Participants may benefit from reading and studying the material or from testing their knowledge by answering the questions. ACCME ACCREDITATION: The American Society for Colposcopy and Cervical Pathology (ASCCP) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. The ASCCP designates this continuing medical education activity for 1-hour Category I credit of the Physician's Recognition Award of the American Medical Association and 1-hour Category I credit of the ASCCP's Program for Continuing Professional Development. Credit is available for those who choose to apply. The Home Study Course is planned and produced in accordance with the ACCME's Essential Areas and Elements.

Adult↗
PubMed2004

Functional attributes of mucosal immunity in cervical intraepithelial neoplasia and effects of HIV infection.

The role of mucosal immunity in human papillomavirus (HPV)-related cervical diseases is poorly understood. To characterize the local immune microenvironment in cervical intraepithelial neoplasia (CIN) 2/3 and determine the effects of HIV infection, we compared samples from three groups: normal cervix, CIN 2/3 from immunocompetent women (HIV- CIN 2/3), and CIN 2/3 from HIV seropositive women (HIV+ CIN 2/3). CIN 2/3 lesions contained increased numbers of immune cells from both the acquired and innate arms of the immune response in stroma [CD4+ and CD8+ T cells, macrophages, mast cells, B cells, neutrophils, and natural killer (NK) cells] and dysplastic epithelium (CD4+ T cells, macrophages, and NK cells). Immune cells in CIN 2/3 expressed activation markers, as measured by interleukin-2 receptor (IL-2R) and transcription factor T bet. Interferon-gamma production was significantly up-regulated in CIN lesions and was expressed by CD4+ and CD8+ T cells and NK cells, indicating the activation of immune cells. Abundant presence of transforming growth factor-beta+ CD25+ cells in the infiltrates associated with CIN lesions, and of immature CD1a+ dendritic cells expressing IL-10 and transforming growth factor-beta, indicate that CIN is associated with an influx of immune cells that produce a mixture of proinflammatory and regulatory cytokines. In HIV+ CIN, immune cell densities (CD4+ T cells, macrophages, neutrophils, and NK cells) and expression of interferon-gamma were significantly decreased compared with HIV- CIN. Regulatory cytokines were also down-regulated in this group. Therefore, both pro- and anti-inflammatory responses present in CIN 2/3 lesions are suppressed in HIV-seropositive women.

Adult↗
PubMed2004

Risk of high-grade squamous intraepithelial lesion in HIV-infected adolescents.

BACKGROUND: The risk of developing the human papillomavirus (HPV)-associated precancer high-grade squamous intraepithelial lesion (HSIL) in human immunodeficiency virus (HIV)-infected adolescents is unknown. We examined the risk of developing HSIL among adolescents with and without HIV infection. METHODS: HIV-infected (n = 172) and -uninfected (n = 84) girls aged 13-18 years who were participating in a multicenter study of primarily horizontally acquired HIV infections in adolescents (Reaching for Excellence in Adolescent Health Care) and who did not have HSIL on cytologic examination at study entry or at the first follow-up visit were followed at 6-month intervals. HIV-uninfected girls were recruited for comparison in a 2:1 ratio (HIV infected:HIV uninfected). The primary outcome was cytologic diagnosis of HSIL confirmed by expert review. RESULTS: Incidence of HSIL by the end of follow-up was higher for HIV-infected girls than for HIV-uninfected girls (21.5% vs. 4.8%, respectively). In multivariate analysis, use of hormonal (either estrogen/progesterone oral combination or medroxyprogesterone acetate intramuscular) contraceptives, high cervical mucous concentrations of interleukin (IL)-12, a positive HPV test, and persistent low-grade squamous intraepithelial lesion (LSIL) were significantly associated with the development of HSIL. CONCLUSIONS: The incidence of HSIL was alarmingly high in HIV-infected adolescent girls. However, when other predictors were considered in multivariate analysis, HIV status was not retained in the model. The heightened risk for HSIL associated with persistent LSIL underscores the need to closely monitor HIV-infected adolescents with LSIL. The risk for HSIL associated with high concentrations of IL-12 may be suggestive of a local immune dysregulation. The role of hormonal contraception as a risk factor deserves further investigation.

Adolescent↗
PubMed2004

Self-collected versus clinician-collected anal cytology specimens to diagnose anal intraepithelial neoplasia in HIV-positive men.

BACKGROUND: Anal intraepithelial neoplasia (AIN) is common in men who have sex with men (MSM) and may be diagnosed by anal cytology screening. METHODS: One hundred two MSM with clinician-collected anal cytology and histopathology specimens were assessed from a cohort study of AIN at the University of California at San Francisco. The men were given a cytology self-collection kit with written instructions for use and requested to collect the sample 1 month after the clinic visit. RESULTS: Ninety-one percent of self-collected and 99% of clinician-collected anal cytology samples were adequate for interpretation. The sensitivity of abnormal anal cytology to detect AIN by histology was 68% in self-collected samples and 70% in clinician-collected samples, and the sensitivity to detect AIN 2 or AIN 3 was 71% and 74%, respectively. Cytologic results did not differ by grade between self-collected and clinician-collected samples. Among MSM diagnosed with AIN 2 or 3 by biopsy, 33% of self-collected and 39% of clinician-collected cytology samples were high-grade. The sensitivity of both self-collected and clinician-collected samples to detect AIN 2 or 3 was higher among HIV-positive MSM than among HIV-negative MSM. CONCLUSIONS: MSM with biopsy-proven AIN can self-collect anal cytology samples with sensitivity comparable with that of experienced clinicians. This may facilitate screening for AIN.

Adult↗
PubMed2004

High prevalence of anal squamous intraepithelial lesions in HIV-positive men despite the use of highly active antiretroviral therapy.

BACKGROUND: The impact of highly active antiretroviral therapy (HAART) on the natural history of HPV infection and anal squamous intraepithelial lesions (SIL) in HIV-infected men who have sex with men (MSM) is poorly documented. GOAL The goal of this study was to evaluate the prevalence of anal HPV infection and SIL inpatients under HAART. STUDY DESIGN: Forty-five HIV-infected protease inhibitor-experienced MSM were enrolled in a cross-sectional study. Each patient provided anal samples for anal cytology, histology, and human papillomavirus (HPV) DNA testing. RESULTS: The patients had previously received HAART for a median of 32 months. Anal cytology was abnormal in 32 of 45 (71%) patients, including high-grade SIL in 10 patients (22%), low-grade SIL in 19 patients (42%), and atypical squamous cells of undetermined significance in 3 patients (7%). HPV DNA was detected 36/45 men (80%). The prevalence of anal SIL and HPV infection were similar in patients exhibiting a significant increase in CD4+ cell count after HAART initiation compared with those who did not. CONCLUSION: Our results demonstrate a high prevalence of anal SIL, including high-grade SIL, and anal HPV infection in HIV-infected MSM despite immune restoration under HAART.

Adult↗
PubMed2003

High prevalence of anal human papillomavirus infection and anal cancer precursors among HIV-infected persons in the absence of anal intercourse.

BACKGROUND: Anal cancer and its precursor lesion, anal squamous intraepithelial lesions (SILs), are associated with human papillomavirus (HPV) infection. Anal HPV infection and anal SIL are common in HIV-positive men who have sex with men; receptive anal intercourse is presumed to be the mode of acquisition of HPV. OBJECTIVE: To assess the prevalence and risk factors for anal HPV infection and anal SIL in HIV-positive men with no history of anal intercourse. DESIGN: Cross-sectional study. SETTING: Hôpital Européen Georges Pompidou outpatient clinic, Paris, France. PATIENTS: 118 HIV-infected men. MEASUREMENTS: 50 HIV-positive heterosexual male injection drug users with no history of anal intercourse and 67 HIV-infected men who had sex with men were evaluated by using anal cytologic, anal histologic, and anal HPV DNA testing. RESULTS: 23 of the 50 heterosexual injection drug users (46%) had anal HPV infection. Low-grade SIL (LSIL) was found in 8 patients (16%) and high-grade SIL (HSIL) in 9 patients (18%). Among the 67 men who had sex with men, anal HPV infection was found in 57 patients (85%), LSIL in 33 patients (49%), and HSIL in 12 patients (18%). In univariate analysis, risk factors for abnormal anal cytologic or histologic findings in injection drug users included CD4+ cell counts less than 250 x 10(6) cells/L (odds ratio, 5.7 [95% CI, 1.6 to 20.4]), plasma HIV RNA viral load greater than 1.7 log copies/mL (odds ratio, 8.9 [CI, 1.1 to 76.0]), previous AIDS-defining event (odds ratio, 4.3 [CI, 1.2 to 15.6]), and anal HPV detection (odds ratio, 5.7 [CI, 1.6 to 20.4]). Risk factors among men who had sex with men included having more than 10 lifetime receptive anal intercourse episodes (odds ratio, 5.6 [CI, 1.6 to 19.8]) and anal HPV detection (odds ratio, 8.7 [CI, 1.9 to 39.0]). CONCLUSIONS: Anal HPV infection and anal SIL may be acquired in the absence of anal intercourse in HIV-positive men. The prevalence of HSIL is high among HIV-positive injection drug users. All HIV-positive men with CD4+ cell counts less than 500 x 10(6) cells/L, regardless of history of anal intercourse, should be considered for anal cytologic screening; however, additional studies are needed to determine the efficacy of this procedure to prevent anal cancer in these populations.

Adult↗
PubMed2003

Human papillomavirus infection and abnormal cytology of the anus in HIV-infected and uninfected adolescents.

OBJECTIVE: To examine the prevalence of and risk for anal human papillomavirus (HPV) infection and abnormal anal cytology in sexually active adolescents. DESIGN: Prevalence data from adolescents aged 13-18 years with and without HIV infection and with a history of high-risk sexual behavior. METHODS: HPV DNA was detected using amplification techniques. Abnormal anal cytology was defined as atypical squamous cell of undetermined significance or worse. RESULTS: Prevalence of anal HPV infection was similar in HIV-infected [28/58 (48%)] and uninfected [9/25 (36%)] boys (P = 0.3). but greater in HIV-infected [59/183 (59%)] than in uninfected [11/82 (13%)] girls (P < 0.001). Perianal warts were a risk for anal HPV in both boys [odds ratio (OR), 15.5; 95% confidence interval (CI), 1.6-149] and girls (OR, 9.9; 95% CI, 1.9-51.3). In subjects without anal warts, HIV infection was significant for girls (OR, 2.3; 95% CI, 1.1-4.9) and homosexual/bisexual orientation was significant for boys (OR, 5.2; 95% CI, 1.3-20.6). Abnormal anal cytology was more common among boys [32/77 (41.6%)] than girls [38/230 (16.5%)] (P < 0.001) and in addition to anal HPV, independent risk factors were positive HIV status in boys (OR, 6.5; 95% CI, 1.5-11.9) and number of partners within the past 3 months in girls (OR, 4.2; 95% CI, 1.5-11.9). CONCLUSIONS: Strong risk factors for abnormal anal cytology were HIV infection and anal HPV in boys and anal HPV and higher number of sexual partners for girls. The results suggest that anal cytology screening should be considered in HIV infected homosexual/bisexual males.

AIDS-Related Opportunistic Infections↗
PubMed2003

The predictive value of cytologic testing in women with the human immunodeficiency virus who have low-grade squamous cervical lesions: a substudy of a randomized, phase III chemoprevention trial.

OBJECTIVE: The purpose of this study was to determine whether the progression of low-grade squamous intraepithelial lesions of the cervix in women with the human immunodeficiency virus can be predicted reliably by standard cytologic testing. STUDY DESIGN: As part of a previously reported trial, 288 biopsy specimens were collected from 117 women with the human immunodeficiency virus. These specimens underwent central and local interpretation, which were compared and correlated with cytologic results. Ninety-two subjects had matched cytologic/histologic pairs at study termination, which were compared to determine whether cytologic testing was predictive of progression. RESULTS: Of the central histologic interpretations, 26 of 288 interpretations (9%) differed from local results, 97 of 246 cytologic/histologic pairs (39%) were discordant, and 21 subjects had progression to high-grade squamous intraepithelial lesions by histologic evidence. Cytologic testing showed high-grade squamous intraepithelial lesions in 4 of 21 specimens (sensitivity, 19%). The remaining cytologic specimens were either low-grade squamous intraepithelial lesions or were normal. CONCLUSION: This substudy of pathologic results from a randomized clinical trial suggests that, although the risk of progression of low-grade squamous intraepithelial lesions is low, follow-up cytologic testing is unreliable. Colposcopic evaluation with directed biopsies should be continued.

Antineoplastic Agents↗
PubMed2003

Incidence of anal cytological abnormalities in a cohort of human immunodeficiency virus-infected women.

Little is known about the natural history of anal human papillomavirus (HPV) infection in HIV-infected women because, to date, no longitudinal studies have been reported in the scientific literature. This article estimates the incidence of anal cytological abnormalities in a cohort of HIV-infected women. It also examines potential risk factors for the development of an anal cytological abnormality. A cohort of HIV-infected women underwent interview, anal cytology, and anogenital HPV DNA testing. Women with a normal baseline anal cytology were followed for the development of an anal cytological abnormality. The incidence of an abnormality was calculated. Survival analyses were performed to examine risk factors for the development of an abnormality. Fourteen of 100 HIV-infected women had an abnormal anal cytology at baseline. Among the 86 women with a normal baseline cytology, the incidence of an abnormality was 22 [95% confidence interval (CI), 14-33] per 100 person-years. In a multivariate analysis, women were at increased risk if, at baseline, they had a CD4+ T-cell count of <500 cells/mm(3) [relative hazard (RH) = 4.11; 95% CI, 1.18-14.25], high-risk type anal HPV infection (RH = 2.54; 95% CI, 0.91-7.14) or were cigarette smokers (RH = 3.88; 95% CI, 1.12-13.42). The incidence of anal cytological abnormalities was high among this cohort of HIV-infected women, indicating that they are at high risk of anal squamous intraepithelial lesions. HIV-infected women are likely to be at higher risk than their HIV-uninfected counterparts because immune suppression conferred substantially increased risk. Continued research on the association between smoking and the development of squamous intraepithelial lesions in HIV-infected women is warranted.

AIDS-Related Opportunistic Infections↗
PubMed2002

Isotretinoin for low-grade cervical dysplasia in human immunodeficiency virus-infected women.

OBJECTIVE: To estimate the efficacy of isotretinoin for prevention of progression of low-grade squamous intraepithelial lesions (SIL) of the cervix to high-grade lesions or invasive cervical cancer; to estimate the regression rate of low-grade SIL with isotretinoin and the toxicity of isotretinoin in this setting; and to correlate serum CD4 levels with progression of low-grade SIL. METHODS: A randomized, phase III, observation-controlled, multicenter trial was performed in which 117 human immunodeficiency virus (HIV)-positive women with low-grade SIL of the cervix received either oral isotretinoin at 0.5 mg/kg per day for 6 months or observation. Papanicolaou smears and colposcopy/biopsy were done at regular intervals during follow-up. The primary endpoint was progression to high-grade SIL or cervical cancer. RESULTS: Twenty-one of 102 women (20.6%) completing follow-up experienced progression to high-grade SIL, 13 in the observation group and eight in the isotretinoin group. This difference was not significant (P =.29). No cases of invasive cancer were seen. Baseline CD4 levels were lower than anticipated (median 329 cells/mm(3)), but not associated with time to progression (P =.36). Most subjects (63 of 102, 61.7%) used highly active antiretroviral therapy. Subjects under age 30 were more likely to progress than those older than 30 (P =.046). CONCLUSION: Isotretinoin was not associated with longer time to progression of low-grade SIL. This appears to be a chronic condition in HIV-positive women, with a low risk of progression and significant rate of resolution. As in the general population, observation without excisional therapy may be appropriate for HIV-positive women with low-grade SIL.

Adult↗
PubMed2002

ASCCP Patient Management Guidelines: Pap Test Specimen Adequacy and Quality Indicators.

OBJECTIVES: To provide management guidelines according to Pap test specimen adequacy based on literature review and expert opinion. METHODS: A task force named by the American Society for Colposcopy and Cervical Pathology conducted a literature review and discussed appropriate management. The steering committee of the American Society for Colposcopy and Cervical Pathology and other experts reviewed the guidelines. RESULTS: The guidelines recommend a repeat Pap test in 12 months for most women who are undergoing routine annual/biennial screening if the current Pap test is negative but either lacks an endocervical/transformation zone component or is partially obscured. Indications for considering an earlier repeat are also provided. The preferred management for unsatisfactory Pap tests is a repeat Pap test within a short interval of 2 to 4 months. CONCLUSIONS: The management guidelines will help promote optimal and uniform follow-up of women's Pap tests, according to Pap test specimen adequacy.

Journal Article↗
PubMed2002

ASCCP patient management guidelines: Pap test specimen adequacy and quality indicators.

Our objective was to provide management guidelines according to Papanicolaou (Pap) test specimen adequacy based on literature review and expert opinion. A task force named by the American Society for Colposcopy and Cervical Pathology (ASCCP) conducted a literature review and discussed appropriate management. The Steering Committee of the ASCCP and other experts reviewed the guidelines. The guidelines recommend a repeated Pap test in 12 months for most women undergoing routine annual/biennial screening if the current Pap test is negative but either lacks an endocervical/ transformation zone component or is partially obscured. Indications for considering an earlier repeat are also provided. The preferred managementfor unsatisfactory Pap tests is a repeated Pap test within a short interval of 2 to 4 months. The management guidelines will help promote optimal and uniform follow-up of women according to Pap test specimen adequacy.

Female↗
PubMed2002

Atypical glandular cells of undetermined significance (AGUS): Interobserver reproducibility in cervical smears and corresponding thin-layer preparations.

Five panelists independently reviewed 135 consecutive conventional cervical smears (CPs) originally classified as atypical glandular cells of undetermined significance (AGUS). A thin-layer slide (TP), prepared from the residual material, also was reviewed in each case. All patients underwent colposcopy that yielded at least 1 histologic specimen. Three or more of 5 reviewers retained the AGUS interpretation for 29% of CPs and 12% of the corresponding TPs. Interobserver variability infrequency of use of AGUS was marked, and interobserver agreement was poor. Agreement was improved for cases cytologically interpreted as a high-grade lesion, especially in TPs. Four of 5 reviewers retained the AGUS classification in CPs for all 7 biopsy-proven neoplastic glandular lesions. Of 95 CP interpretations made by 5 reviewers in the 19 histologically diagnosed high-grade lesions, 8 were "negative/reactive" and 6 were AGUS "favor reactive." AGUS is a poorly reproducible cytologic interpretation. Although most neoplastic glandular lesions may be distinguished by cytopathologists experienced in this area from mimics originally considered AGUS, attempts to increase the diagnostic specificity of AGUS may diminish sensitivity for an underlying high-grade precursor. Interobserver agreement was better for TPs than for the corresponding CPs. However, the split-sample TP slides may not have been fully comparable to the CPs.

Adenocarcinoma↗