Biomedical subjects

Teresa Darragh

Publications and source records attributed to Teresa Darragh.

9 recordsLinked to original sources

PubMed2005

Age-related prevalence of anal cancer precursors in homosexual men: the EXPLORE study.

BACKGROUND: Infection with human papillomavirus (HPV) is causally linked to the development of anal and cervical cancer. In the United States, the incidence of anal cancer among men who have sex with men (MSM) is higher than the incidence of cervical cancer among women. Anal squamous intraepithelial lesions (ASILs) are anal cancer precursors comprising low-grade squamous intraepithelial lesions (LSILs) and high-grade squamous intraepithelial lesions (HSILs). The prevalence of cervical cancer precursor lesions peaks at around 30 years of age. The age-related prevalence of ASILs in HIV-negative MSM is unknown. METHODS: We conducted a cross-sectional analysis of the prevalence and determinants of ASILs in 1262 HIV-negative MSM aged 18-89 years recruited from four U.S. cities. Anal cytology and behavioral data were obtained. Anal HPV infection status was assessed by polymerase chain reaction. Independent predictors of ASILs were identified using logistic regression. All statistical tests were two-sided. RESULTS: The prevalences of LSILs and HSILs were 15% and 5%, respectively, and did not change with age. In a multivariable analysis, the risk of LSILs was associated with having more than five male receptive anal sex partners (P = .03), any use of poppers (alkyl nitrites) in the previous 6 months [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.1 to 2.5; P = .03] or use of injection drugs two or more times per month during the previous 6 months [OR = 19, 95% CI = 1.3 to 277; P = .03], older age at first receptive anal intercourse (P = .004), and infection with a greater number of HPV types (P < .001 for linear trend). The risk of HSILs was associated with any anal HPV infection (OR = 3.2, 95% CI = 1.1 to 9.4; P = .039) and infection with an increasing number of HPV types (P < .001 for linear trend). CONCLUSIONS: Sexually active HIV-negative MSM in all age groups have a high prevalence of ASILs, possibly reflecting their ongoing sexual exposure to HPV.

Adult↗

PubMed2005

Interobserver agreement in the interpretation of anal intraepithelial neoplasia.

BACKGROUND: Anal carcinoma incidence is increasing, and is highest among men with human immunodeficiency virus (HIV) infection who have sex with men. Anal carcinoma and anal intraepithelial neoplasia (AIN) are ascertained on tissue histology, but requires invasive procedures. Screening for AIN using anal cytology was suggested. The authors evaluated agreement on cytologic and biopsy specimens from HIV-positive men undergoing anal carcinoma screening. METHODS: One hundred twenty-nine HIV-positive men with a history of anal-receptive intercourse underwent anal cytology, anoscopy, and biopsy. Four pathologists independently assessed cytology and biopsy specimens and reached consensus for discordant cases. RESULTS: Each pathologist evaluated 120 cytology and 155 biopsy specimens. The weighted kappa value for overall agreement was 0.54 (95% confidence interval [CI], 0.49-0.59) for cytology specimens and 0.59 (95%CI, 0.55-0.63) for biopsy specimens. The median kappa values for pairwise agreement among pathologists and for agreement with consensus were, respectively, 0.69 and 0.77 for cytology and 0.66 and 0.75 for biopsy. At least 3 pathologists were in agreement for 92 (76.7%) cytology and 134 (86.5%) biopsy specimens. Reliability for the Bethesda classification system was at least moderate, except for the cytologic category of atypical squamous cells of undetermined significance (kappa = 0.12). Fourteen of 29 (48.3%) cytology specimens and 36 of 47 (76.6%) biopsy specimens with consensus interpretation of high-grade squamous intraepithelial lesions (HSIL) were interpreted originally as HSIL by > or = 3 pathologists. The kappa value for agreement with consensus distinguishing HSIL from non-HSIL ranged from 0.55 to 0.88 for cytology specimens and from 0.76 to 0.94 for biopsy specimens. CONCLUSIONS: Agreement for cytologic and biopsy interpretations was generally at least moderate. Nevertheless, these results supported the need for disease indicators with greater reliability.

Adolescent↗

PubMed2005

Outcome after negative colposcopy among human immunodeficiency virus-infected women with borderline cytologic abnormalities.

OBJECTIVE: To estimate the risk of and risk factors for progression among human immunodeficiency virus (HIV)-seropositive women with abnormal cervical cytology but negative colposcopy. METHODS: In a prospective cohort study, 391 HIV-seropositive and 103 seronegative women with cervical cytology read as atypical squamous cells (ASC) or low-grade squamous intraepithelial lesion (LSIL) but negative colposcopy were followed up for a mean of 4.0 years with cytology at 6-month intervals. Colposcopy was prescribed for any epithelial abnormality. RESULTS: Progression to CIN2, CIN3, high-grade SIL/severe dysplasia, or cancer occurred in 47 (12%) HIV-seropositive women and 4 (4%) HIV-seronegative women (P = .02). Progression to CIN1 was seen in an additional 12 HIV-seropositive women and 1 seronegative woman. In multivariate analysis, high-risk but not low-risk HPV detection (hazard ratio [HR] 2.46-95% confidence interval [CI] 1.18-5.12, P = .02 for high risk, HR 1.41, 95% CI 0.62-3.21, P = .42 for low risk), satisfactory colposcopy (HR 2.01, 95% CI 1.11-3.65, P = .02), and non-Hispanic African-American ethnicity (HR 5.08, 95% CI 1.72-14.98, P = .003) were the only factors associated with progression, while HIV serostatus was marginally significant (HR 2.53, 95% CI 0.85-7.50, P = .09). CONCLUSION: Human immunodeficiency virus-seropositive women with negative colposcopy after borderline cytology face a higher risk of progression than seronegative women, but the absolute risk is low and becomes nonsignificant after controlling for HPV risk type, ethnicity, and colposcopic findings. Observation is appropriate. LEVEL OF EVIDENCE: II-2.

Adult↗

PubMed2005

Assisted primary screening using the automated ThinPrep Imaging System.

We report the clinical trial studies for the ThinPrep Imaging System (TIS; Cytyc, Boxborough, MA). Between December 2000 and July 2001, 10,742 ThinPrep specimens were collected at 4 US clinical sites representative of the normal clinical population of the laboratories, including screening patients and referred patients. After nonstudy screening diagnoses were completed, the vials were relabeled and randomized, and study slides were prepared and stained. TIS-trained cytotechnologists and pathologists screened the slides twice, first manually, then TIS-assisted after an appropriate interval. Afterward, 3 independent pathologists performed an adjudication study to determine definitive diagnoses for the nonnegative slides and 5% of the negative slides; the adjudicated diagnoses served as the "gold standard" for subsequent sensitivity and specificity analyses. TIS-assisted screening was statistically more sensitive than manual screening for atypical squamous cells of undetermined significance (ASCUS) or higher (+) and statistically equivalent for low- (LSIL)+ and high-grade squamous intraepithelial lesion (HSIL)+ diagnoses. TIS-assisted screening had equivalent specificity for ASCUS+ and LSIL+ and significantly higher specificity for HSIL+. Average cytologists' daily screening rates doubled with TIS-assisted screening. The sensitivity of the TIS-assisted screening system equals or exceeds the sensitivity of manual primary screening without adversely affecting specificity, and TIS-assisted screening can improve cervical cancer screening productivity. Cost issues require further study.

Female↗

PubMed2004

Age-Specific prevalence of anal human papillomavirus infection in HIV-negative sexually active men who have sex with men: the EXPLORE study.

BACKGROUND: In the United States, anal cancer in men who have sex with men (MSM) is more common than cervical cancer in women. Human papillomavirus (HPV) is causally linked to the development of anal and cervical cancer. In women, cervical HPV infection peaks early and decreases after the age of 30. Little is known about the age-specific prevalence of anal HPV infection in human immunodeficiency virus (HIV)-negative MSM. METHODS: We studied the prevalence and determinants of anal HPV infection in 1218 HIV-negative MSM, 18-89 years old, who were recruited from 4 US cities. We assessed anal HPV infection status by polymerase chain reaction. RESULTS: HPV DNA was found in the anal canal of 57% of study participants. The prevalence of anal HPV infection did not change with age or geographic location. Anal HPV infection was independently associated with receptive anal intercourse (odds ratio [OR], 2.0; P<.0001) during the preceding 6 months and with >5 sex partners during the preceding 6 months (OR, 1.5; P<.0001). CONCLUSIONS: Urban, HIV-negative MSM have a stable, high prevalence of anal HPV infection across all age groups. These results differ substantially from the epidemiologic profile of cervical HPV infection in women. This may reflect differences between these populations with respect to the number of new sex partners after the age of 30 and may explain the high incidence of anal cancer in MSM.

Adult↗

PubMed2004

Natural history of grade 1 cervical intraepithelial neoplasia in women with human immunodeficiency virus.

OBJECTIVE: We sought to estimate rates of progression and regression of grade 1 cervical intraepithelial neoplasia (CIN 1) among women with human immunodeficiency virus (HIV). METHODS: In a multicenter prospective cohort study, HIV-seropositive and HIV-seronegative women were evaluated colposcopically after receiving an abnormal cytology test result between November 1994 and September 2002. Women with CIN 1 were included, except those who had undergone hysterectomy, cervical therapy, or had CIN 2-3 or cervical cancer. Those women who were included were followed cytologically twice yearly, with colposcopy repeated for atypia or worse. RESULTS: We followed 223 women with CIN 1 (202 HIV seropositive and 21 HIV seronegative) for a mean of 3.3 person-years. Progression occurred in 8 HIV-seropositive women (incidence density, 1.2/100 person-years; 95% confidence interval [CI] 0.5-2.4/100 person-years) and in no HIV seronegative women. Regression occurred in 66 (33%) HIV-seropositive women (13/100 person-years, 95% CI 10-16/100 person-years) versus 14 (67%) seronegative women (32/100 person-years, relative risk 0.40, 95% CI 0.25-0.66; P < .001). In multivariate analysis, regression was associated with human papillomavirus (HPV) detection (hazard ratio [HR] for low risk 0.28, 95% CI 0.13-0.61, P = .001; and for high-risk 0.34, 95% CI 0.20-0.55, P < .001 versus no HPV detected) and Hispanic ethnicity (HR 0.48, 95% CI 0.230.98; P = .04); HIV serostatus was only marginally linked to regression (HR 0.52, 95% CI 0.27-1.03; P = .06), but seropositive women were less likely to regress when analysis was limited to 146 women with HPV detected at CIN 1 diagnosis (HR 0.18, 95% CI 0.05-0.62; P = .006). CONCLUSION: Grade 1 cervical intraepithelial neoplasia infrequently progresses in women with HIV. Thus, observation appears safe absent other indications for treatment. LEVEL OF EVIDENCE: II-1.

Adult↗

PubMed2003

Utility of cervicography in HIV-infected and uninfected adolescents.

PURPOSE: To compare cytology with cervicography in HIV-infected and uninfected adolescent females. METHODS: At the time of analysis, 334 girls aged 13-19 years from 13 U.S. cities were participating in a prospective study of HIV infection. All subjects had cytology and a Cervigram (cervicography) performed at two consecutive visits 6 months apart, referred to as visit (V) 1 and 2. Cervigrams were sent to the parent company for diagnosis and were categorized as: "negative" or "positive" (compatible with low-grade or high-grade squamous intraepithelial lesions [SIL]). Cytology was considered abnormal if the subject had SIL at either V1 or V2. Sensitivity, specificity, and positive predictive value (PPV) of the Cervigram were calculated compared with repeat Papanicolaou (Pap) smears. RESULTS: Two consecutive adequate Pap smears were available for analysis in 200 adolescents; 51% (95% CI, 43-59) of the 142 HIV-positive youth and 19% (95% CI, 9-29) of the 58 HIV-negative youth had SIL on at least one Pap smear (p < .001). A positive Cervigram was observed in 44% (95% CI, 36-53) of the HIV-infected group and 29% (95% CI, 17-41) of the HIV-uninfected group (p =.06). For the HIV-infected group, the sensitivity, specificity, and PPV of the Cervigram to detect SIL were 58% (95% CI, 45-71), 69% (95%CI, 57-80), and 64% (95%CI, 52-77), respectively. For the HIV-uninfected group, the sensitivity, specificity, and PPV were 64% (95% CI, 31-89), 80% (95% CI, 65-90), and 44% (95% CI, 19-68), respectively. The combined sensitivity, using both the Pap smear and Cervigram result from V1 to detect SIL, was 82% (95% CI, 71-91 for HIV+ and 48-98 for HIV-) in both groups. However, the PPV based the performance of the Cervigram in Pap smear-negative women as 33% (95% CI, 17-53) and 15% (95% CI, 2-45) for the HIV-infected and uninfected group, respectively (p = not significant [ns]). CONCLUSIONS: Although the sensitivity of a single Pap smear increased significantly when the Cervigram was used as an adjunct, the low PPV in both HIV-infected and uninfected groups, suggests that cervicography has a limited utility for precancer and cervical cancer screening in high-risk adolescent populations.

Adolescent↗

PubMed2002

Lymphoid follicles are generated in high-grade cervical dysplasia and have differing characteristics depending on HIV status.

The exact role of the mucosal immune response in the pathogenesis of human papillomavirus (HPV)-related premalignant and malignant diseases of the genital tract is poorly understood. We used immunohistochemical analysis to characterize immune cells in normal cervix (N = 21), HIV-negative high-grade dysplasia (N = 21), and HIV-positive high-grade dysplasia (N = 30). Classical germinal centers were present in 4.7% of normal cervix, 33% of high-grade lesions from HIV-negative women, and 3.3% of high-grade lesions from HIV-positive women (P = 0.003). HPV16 E7 antigen was detected in a subset of germinal centers, indicating that the secondary immune response was directed in part against HPV. Lymphoid follicles were present in 9.5% of normal cervix, 57% of HIV-negative high-grade dysplasia, and 50% of HIV-positive high-grade dysplasia (P = 0.001 normal versus high-grade). A novel type of lymphoid aggregate, consisting predominantly of CD8(+) T cells, was detected in 4.8% of normal cervix, 0% of HIV-negative high-grade dysplasia, and 40% of HIV-positive high-grade dysplasia (P < 0.001). The recurrence rate of high-grade dysplasia within one year was significantly higher in women with such CD8(+) T cell-dominant aggregates (P = 0.02). In summary, the types of lymphoid follicle in lesions from HIV-positive women were significantly different from those from HIV-negative women, and these differences are associated with the worse clinical outcome in HIV-positive women.

Adult↗

PubMed2002

Encapsulated plasmid DNA treatment for human papillomavirus 16-associated anal dysplasia: a Phase I study of ZYC101.

High-grade dysplasia induced by high-risk types of human papillomavirus (HPV) precedes invasive cancer in anal squamous epithelium just as it does in the cervix. A therapeutic HPV vaccine strategy as a potential treatment for anal dysplasia was tested in a standard Phase I dose escalation trial. The primary objective was to evaluate the safety of the agent; additional study aims were to evaluate the histological response, immune response, and effect on anal HPV-16 infection. Each subject was treated with four i.m. injections of 50-400 microg of ZYC101 at 3-week intervals. ZYC101 is composed of plasmid DNA encapsulated in biodegradable polymer microparticles. The plasmid DNA encodes for multiple HLA-A2-restricted epitopes derived from the HPV-16 E7 protein, one of two HPV oncoproteins consistently expressed in neoplastic cells. Fifty-six potential anal dysplasia subjects were screened to identify 12 eligible subjects with HPV-16 anal infection and a HLA-A2 haplotype. The investigational agent was well tolerated in all subjects at all dose levels tested. Three subjects experienced partial histological responses, including one of three subjects receiving the 200-microg dose and two subjects at the 400-microg dose level. Using a direct Elispot, 10 of 12 subjects demonstrated increased immune response to the peptide epitopes encoded within ZYC101; each continued to show elevated immune responses 6 months after the initiation of therapy. These results support the continued investigation of a therapeutic vaccination strategy for anal dysplasia.

Adult↗