PubMed Health⌕ Search

Biomedical subjects

Catherine Hankins

Publications and source records attributed to Catherine Hankins.

At least 19 recordsLinked to original sources
PubMed2007

Polymorphism of the L1 capsid gene and persistence of human papillomavirus type 52 infection in women at high risk or infected by HIV.

HIV-seropositive women are at increased risk for human papillomavirus (HPV) infection, which causes high-grade squamous intraepithelial lesions (HSILs). HPV-52 is a frequent HPV type in Canadian HIV-seropositive women. Because variations of the capsid gene, designated the L1 gene, could elicit immune responses that result in different efficiencies in eliminating HPV, we described HPV-52 polymorphism and assessed whether it was associated with HPV-52 persistence in 114 women at risk or infected by HIV. Nonsynonymous variations were more frequent in the 5 putative hypervariable regions (exposed loops of L1 protein) (10 [3.2%] variations over 311 nucleotides) than in nonvariable regions (4 [0.3%] variations over 1278 nucleotides; P < 0.0001). Synonymous variations were distributed evenly between hypervariable regions (10 [3.2%] variations over 311 nucleotides) and nonvariable regions (46 [3.6%] variations over 1278 nucleotides; P = 0.88). Nonprototype (nonreference) L1 variants were detected more frequently in women of African descent (24 [60.0%] of 40 women) than in white women (23 [37.1%] of 62 women, odds ratio = 2.54, 95% confidence interval: 1.11 to 5.81; P = 0.03). In contrast to previous findings that polymorphism in the long control region (LCR) was associated with HPV-52 persistence, L1 capsid variations were not associated with persistence (P = 0.45). L1 variations are unlikely to predispose to HPV-52 persistence and thus do not help to identify women at greater risk for HSILs.

Adult↗
PubMed2006

The global impact of scaling up HIV/AIDS prevention programs in low- and middle-income countries.

A strong, global commitment to expanded prevention programs targeted at sexual transmission and transmission among injecting drug users, started now, could avert 28 million new HIV infections between 2005 and 2015. This figure is more than half of the new infections that might otherwise occur during that period in 125 low- and middle-income countries. Although preventing these new infections would require investing about U.S.$122 billion over this period, it would reduce future needs for treatment and care. Our analysis suggests that it will cost about U.S.$3900 to prevent each new infection, but that this will produce a savings of U.S.$4700 in forgone treatment and care costs. Thus, greater spending on prevention now would not only prevent more than half the new infections that would occur from 2005 to 2015 but would actually produce a net financial saving as future costs for treatment and care are averted.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Towards universal access to HIV prevention, treatment, care, and support: the role of tuberculosis/HIV collaboration.

Tuberculosis is the oldest of the world's current pandemics and causes 8.9 million new cases and 1.7 million deaths annually. The disease is among the most common causes of morbidity and mortality in people living with HIV. However, tuberculosis is more than just part of the global HIV problem; well-resourced tuberculosis programmes are an important part of the solution to scaling-up towards universal access to comprehensive HIV prevention, diagnosis, care, and support. This article reviews the impact of the interactions between tuberculosis and HIV in resource-limited settings; outlines the recommended programmatic and clinical responses to the dual epidemics, highlighting the role of tuberculosis/HIV collaboration in increasing access to prevention, diagnostic, and treatment services; and reviews progress in the global response to the epidemic of HIV-related tuberculosis.

AIDS-Related Opportunistic Infections↗
PubMed2006

Enhanced detection and typing of human papillomavirus (HPV) DNA in anogenital samples with PGMY primers and the Linear array HPV genotyping test.

The Roche PGMY primer-based research prototype line blot assay (PGMY-LB) is a convenient tool in epidemiological studies for the detection and typing of human papillomavirus (HPV) DNA. This assay has been optimized and is being commercialized as the Linear Array HPV genotyping test (LA-HPV). We assessed the agreement between LA-HPV and PGMY-LB for detection and typing of 37 HPV genotypes in 528 anogenital samples (236 anal, 146 physician-collected cervical, and 146 self-collected cervicovaginal swabs) obtained from human immunodeficiency virus-seropositive individuals (236 men and 146 women). HPV DNA was detected in 433 (82.0%) and 458 (86.7%) samples with PGMY-LB and LA-HPV (P = 0.047), respectively, for an excellent agreement of 93.8% (kappa = 0.76). Of the 17,094 HPV typing results, 16,562 (1,743 positive and 14,819 negative results) were concordant between tests (agreement = 96.9%; kappa = 0.76). The mean agreement between tests for each type was 96.4% +/- 2.4% (95% confidence interval [CI], 95.6% to 97.2%; range, 86% to 100%), for an excellent mean kappa value of 0.85 +/- 0.10 (95% CI, 0.82 to 0.87). However, detection rates for most HPV types were greater with LA-HPV. The mean number of types per sample detected by LA-HPV (4.2 +/- 3.4; 95% CI, 3.9 to 4.5; median, 3.0) was greater than that for PGMY-LB (3.4 +/- 3.0; 95% CI, 3.1 to 3.6; median, 2.0) (P < 0.001). The number of types detected in excess by LA-HPV in anal samples correlated with the number of types per sample (r = 0.49 +/- 0.06; P = 0.001) but not with patient age (r = 0.03 +/- 0.06; P = 0.57), CD4 cell counts (r = 0.06 +/- 0.06; P = 0.13), or the grade of anal disease (r = -0.11 +/- 0.06; P = 0.07). LA-HPV compared favorably with PGMY-LB but yielded higher detection rates for newer and well-known HPV types.

Adolescent↗
PubMed2006

The potential impact of male circumcision on HIV in Sub-Saharan Africa.

BACKGROUND: A randomized controlled trial (RCT) has shown that male circumcision (MC) reduces sexual transmission of HIV from women to men by 60% (32%-76%; 95% CI) offering an intervention of proven efficacy for reducing the sexual spread of HIV. We explore the implications of this finding for the promotion of MC as a public health intervention to control HIV in sub-Saharan Africa. METHODS AND FINDINGS: Using dynamical simulation models we consider the impact of MC on the relative prevalence of HIV in men and women and in circumcised and uncircumcised men. Using country level data on HIV prevalence and MC, we estimate the impact of increasing MC coverage on HIV incidence, HIV prevalence, and HIV-related deaths over the next ten, twenty, and thirty years in sub-Saharan Africa. Assuming that full coverage of MC is achieved over the next ten years, we consider three scenarios in which the reduction in transmission is given by the best estimate and the upper and lower 95% confidence limits of the reduction in transmission observed in the RCT. MC could avert 2.0 (1.1-3.8) million new HIV infections and 0.3 (0.1-0.5) million deaths over the next ten years in sub-Saharan Africa. In the ten years after that, it could avert a further 3.7 (1.9-7.5) million new HIV infections and 2.7 (1.5-5.3) million deaths, with about one quarter of all the incident cases prevented and the deaths averted occurring in South Africa. We show that a) MC will increase the proportion of infected people who are women from about 52% to 58%; b) where there is homogenous mixing but not all men are circumcised, the prevalence of infection in circumcised men is likely to be about 80% of that in uncircumcised men; c) MC is equivalent to an intervention, such as a vaccine or increased condom use, that reduces transmission in both directions by 37%. CONCLUSIONS: This analysis is based on the result of just one RCT, but if the results of that trial are confirmed we suggest that MC could substantially reduce the burden of HIV in Africa, especially in southern Africa where the prevalence of MC is low and the prevalence of HIV is high. While the protective benefit to HIV-negative men will be immediate, the full impact of MC on HIV-related illness and death will only be apparent in ten to twenty years.

Africa South of the Sahara↗
PubMed2005

Self-sampling is associated with increased detection of human papillomavirus DNA in the genital tract of HIV-seropositive women.

BACKGROUND: Analysis of self-collected swab samples from the genital tract could improve accrual and retention of women in studies of human papillomavirus (HPV) infection and precancerous cervical lesions. Self-collected vaginal swab specimens and physician-collected cervical swab specimens were compared for detection and typing of HPV DNA in 158 HIV-seropositive women. METHODS: Paired samples were collected for 157 participants. Beta-globin was not detected in 6 (3.3%) physician-collected specimens and 8 (4.3%) self-obtained specimens collected from 11 women, leaving 146 paired samples suitable for PCR analysis. HPV DNA was amplified with the HPV primers PGMY09 and PGMY11 and typed using the line blot assay. RESULTS: HPV DNA was detected more frequently in self-collected samples (95 [65.1%] of 146), compared with physician-collected samples (78 [53.4%] of 146) (P = .04). Self-collected samples contained a greater number of types (mean +/- SD, 1.60 +/- 1.80 types; 95% confidence interval [CI], 1.31-1.90), compared with physician-collected samples (mean +/- SD, 1.25 +/- 1.66 types; 95% CI, 0.98-1.52) (P = .04). A good agreement between sampling methods was achieved for detection of any HPV DNA (kappa = 0.73; 95% CI, 0.58-0.89), high-risk types (kappa = 0.84; 95% CI, 0.68-0.99), and low-risk types (kappa = 0.71; 95% CI, 0.67-0.75). Agreement between sampling methods for detection of HPV DNA was found for 24 (88.8%) of 27 follow-up samples collected from a total of 20 women. A comparison of samples collected at consecutive visits revealed agreements for detection of any HPV DNA, detection of high-risk HPV, and HPV typing results between visits of 88.9% (24 of 27 samples), 81.5% (22 of 27), and 55.5% (15 of 27), respectively, for physician-collected samples, and 96.3% (26 of 27 samples), 92.6% (25 of 27), and 55.5% (15 of 27), respectively, for self-collected samples. CONCLUSION: Analysis of self-collected vaginal swab samples improved the detection rate of HPV, suggesting that such samples might be of greater value than physician-obtained samples in studies of HPV transmission.

Adolescent↗
PubMed2005

High levels of HPV-16 DNA are associated with high-grade cervical lesions in women at risk or infected with HIV.

OBJECTIVE: To examine associations between levels of episomal and integrated human papillomavirus (HPV) 16 DNA and the grade of cervical disease. DESIGN: Cross-sectional data were obtained from a cohort of women with and without HIV infection and with high-risk sexual behaviour. METHODS: Episomal and integrated HPV-16 DNA loads were measured in cervicovaginal lavages collected from 75 women (58 HIV seropositive, 17 HIV seronegative) using real-time polymerase chain reaction assays, controlling for cell content and the presence of inhibitors. RESULTS: HPV-16 viral loads were significantly higher in women with high-grade squamous intraepithelial lesions (n = 6) than in women with normal cytology (n = 44), whether total (10(8.28) versus 10(5.10) HPV-16 DNA copies/microg DNA), episomal (10(7.99) versus 10(4.61)) or integrated (10(7.95) versus 10(4.77)) HPV-16 viral loads were measured (P < 0.02 for each comparison). Thirty-nine women had colposcopy [11 normal cervix, 16 cervical intraepithelial neoplasia (CIN) 1, six CIN 2, six CIN 3] and 24 additional women had three consecutive normal cytology smears. Controlling for age, race, CD4 cell count and HIV status, total (OR 3.5, 95% CI 1.2-10.4; P = 0.02), episomal (OR 2.9, 95% CI 1.2-7.4; P = 0.02,) and integrated (OR 1.6, 95% CI 1-2.6; P = 0.05) HPV-16 DNA loads were significantly associated with CIN 2,3, but the differences between CIN 1 and CIN 2,3 were not significant (P > 0.06). A greater amount of cellular DNA was collected from women with CIN 2,3 (P = 0.007). CONCLUSION: Higher HPV-16 DNA loads are associated with cervical lesions detected by either histology or cytology. No additional information is gained by measuring integrated or episomal over total HPV-16 DNA loads.

Adult↗
PubMed2005

Polymorphism of human papillomavirus type 31 isolates infecting the genital tract of HIV-seropositive and HIV-seronegative women at risk for HIV infection.

The genomic polymorphism of high-risk human papillomavirus (HPV) for types other than 16 has not been extensively described. We describe here the genomic polymorphism of high-risk HPV type 31 in 79 women (62 HIV-seropositive, 17 HIV-seronegative) by PCR-sequencing of the long control region (LCR), E6 and E7. LCR polymorphism was generated by 25 (6.4%) single-nucleotide variations over 391 bases. Each variant compared to the prototype contained from 2 to 13 variations (mean of 9.4 +/- 3.3, median of 10). Considering the number of variation sites in each region of HPV genome, the LCR was more variable than E6 (13 over 496 nucleotide (nt), P=0.03) and E7 (9 over 296 nt, P=0.03). Non-synonymous nucleotide variations were found in 31 (75.6%) of 41 isolates and were observed at six positions in E6. Each of the 8 HPV-31 E7 variants contained from 2 to 5 mutations (mean of 4.29 +/- 1.11, median of 5) compared to the prototype. Three non-synonymous E6 and E7 variations were within cysteine arrays. The LCR prototype was significantly over-represented in Caucasian women (14 (25%) of 56) compared to women of African descent (0 (0%) of 15 women, P=0.03). Four (23.5%) of 17 women with persistent versus 6 (25.0%) of 24 women with transient infections were infected by the prototype (P=1.00). HPV-31 LCR was more polymorphic than oncogenes and was associated with ethnicity.

Base Sequence↗
PubMed2005

High level of correlation of human papillomavirus-16 DNA viral load estimates generated by three real-time PCR assays applied on genital specimens.

Human papillomavirus-16 (HPV-16) viral load could be a biomarker predictive of the presence of high-grade cervical lesions. Recently, several real-time PCR assays have been developed to accurately measure HPV-16 viral load. However, results from various reports using these assays cannot be compared because interassay test correlation has not been documented. The variability of HPV-16 DNA quantitation was assessed by comparing three real-time PCR assays (HPV-16 L1, HPV-16 E6, and HPV-16 E6 PG) applied on 144 genital samples (125 cervicovaginal lavages and 19 specimens collected using vaginal tampons) obtained from 84 women (66 HIV seropositive and 18 HIV seronegative). Correlation was greater between the HPV-16 E6 assays [correlation coefficient (rho) = 0.92] than between each E6 assay and HPV-16 L1 assay (rho = 0.83 and 0.84, respectively). The median HPV-16 copies measured by HPV-16 E6 PG (14,609 HPV-16 copies/2 muL sample) and HPV-16 E6 (18,846 HPV-16 copies/2 muL) were similar (P = 0.27) but were both greater than the median HPV-16 copies measured with the L1 assay (4,124 HPV-16 copies/2 muL; P < 0.001). Correlations between HPV-16 E6 assays were similar for samples containing non-European (rho = 0.93) or European (rho = 0.95) variants. However, the correlation between HPV-16 L1 and HPV-16 E6 PG or HPV-16 E6 was lower for specimens containing non-European variants (rho = 0.80 and 0.76, respectively) compared with specimens containing European variants (rho > 0.85). HPV-16 DNA quantity estimated with the three assays was comparable although lower with the HPV-16 L1 assay. The level of correlation depended on viral polymorphism, viral load, and cervical disease status.

Adolescent↗
PubMed2004

Viral polymorphism in human papillomavirus types 33 and 35 and persistent and transient infection in the genital tract of women.

BACKGROUND: Genetic polymorphism in human papillomavirus (HPV)-33 and -35 was investigated in 1055 sexually active women (732 human immunodeficiency virus [HIV] seropositive and 323 HIV seronegative). METHODS: Consecutive genital specimens obtained at 6-month intervals were screened for HPV-33 and -35 by use of MY09-MY11. HPV-33 and -35 isolates from 95 women were analyzed by polymerase chain reaction sequencing of the long control region (LCR), E6, and E7. RESULTS: For HPV-33, 101 (20%) of 506 nucleotides in the LCR were variable, compared with 10 (2.1%) of 483 nucleotides in E6 (P<.001) and 6 (1.9%) of 324 nucleotides in E7 (P<.001). For HPV-35, the proportion of variable nucleotide sites was similar between the LCR and both E6 (P=.54) and E7 (P=.33). The presence of a 78-base pair deletion in HPV-33 (relative risk [RR], 1.8 [95% confidence interval [CI], 1.2-2.7]) and the presence of nonsynonymous E7 variations in HPV-35 (RR, 2.6 [95% CI, 1.4-4.6]) were associated with persistence. When the data for HPV-33 and -35 were combined, infection by HPV isolates with nonsynonymous E7 variations (RR, 2.3 [95% CI, 1.6-3.4]; P=.001) and ethnicity (P=.04) were associated with persistence, whereas age (P = .14) and HIV infection/CD4 cell count status (P=.12) were not significantly associated with persistence, by logistic regression analysis. CONCLUSION: HPV-33 and -35 polymorphism was different between types and was associated with persistence of HPV infection.

Adult↗
PubMed2004

Genomic polymorphism of human papillomavirus type 52 predisposes toward persistent infection in sexually active women.

We investigated the role of human papillomavirus (HPV) type 52 polymorphism in the persistence of HPV infection, which is a predictor for cervical lesions. Cervical samples obtained at 6-month intervals were tested for HPV-52 in 1055 women; 41, 12, and 58 women had persistent, transient, and unclassified HPV-52 infections, respectively. HPV-52 isolates were analyzed by polymerase chain-reaction sequencing of the long control region (LCR), E6, and E7 genes. Although age (odds ratio [OR], 0.90 [95% confidence interval [CI], 0.81-0.99]), nonprototypic LCR (OR, 9.26 [95% CI, 2.1-41.7]), and E6 variant (OR, 7.04 [95% CI, 1.4-37]) were associated, in univariate analysis, with the persistence of HPV-52 infection, a nonprototypic LCR variant was the only independent predictor of it (OR, 14.1 [95% CI, 1.1-200]). In the latter variants, the loss of a binding site for a repressor of HPV expression was associated with the persistence of HPV infection (OR, 7.25 [95% CI, 1.67-31.25]).

Adult↗
PubMed2004

Transmission of HIV-1 infection in sub-Saharan Africa and effect of elimination of unsafe injections.

During the past year, a group has argued that unsafe injections are a major if not the main mode of HIV-1 transmission in sub-Saharan Africa. We review the main arguments used to question the epidemiological interpretations on the lead role of unsafe sex in HIV-1 transmission, and conclude there is no compelling evidence that unsafe injections are a predominant mode of HIV-1 transmission in sub-Saharan Africa. Conversely, though there is a clear need to eliminate all unsafe injections, epidemiological evidence indicates that sexual transmission continues to be by far the major mode of spread of HIV-1 in the region. Increased efforts are needed to reduce sexual transmission of HIV-1.

Adolescent↗
PubMed2004

Prevalence of selective inhibition of HPV-16 DNA amplification in cervicovaginal lavages.

HPV-16 viral load has been assessed with real-time PCR assays by measuring HPV-16 DNA and a human gene in genital samples. HPV-16 viral load measurements are thus based on the inference that inhibitors contained in samples will equally impede amplification of DNA sequences from HPV-16 and human DNA. We have previously shown that sample lysates can inhibit amplification of HPV-16 but not beta-globin DNA. In the current study, cervicovaginal lavages lysates considered adequate for PCR analysis by a qualitative beta-globin PCR test, were screened for the presence of inhibitors using internal controls (IC) for HPV-16 DNA and beta-globin in real-time PCR assays. Of 150 lysates screened with both ICs, 12 (8%) contained inhibitors. Inhibition of amplification of both ICs was demonstrated in four of these specimens. In eight lysates, amplification of HPV-16 IC only was impeded. Six (50%) of these 12 lysates tested positive for HPV-16 DNA despite the presence of PCR inhibitors. The HPV-16 viral load increased significantly after dilution of 11 of 12 lysates, demonstrating the presence of inhibitors in the undiluted lysate. Nine (90%) of 10 samples with inhibitors that were tested after dilution did not demonstrate inhibitory activity. The use of internal controls in real-time PCR is clearly essential to determine HPV viral loads since the effect of inhibitors on primer-driven genomic amplification is variable.

Cervix Uteri↗
PubMed2004

Human papillomavirus type 16 viral load is higher in human immunodeficiency virus-seropositive women with high-grade squamous intraepithelial lesions than in those with normal cytology smears.

Human papillomavirus type 16 (HPV-16) viral load in cervicovaginal lavage samples collected from 66 human immunodeficiency virus-seropositive women was inversely correlated with blood CD4 count (P = 0.002). HPV-16 viral load was 81-fold higher in women with cervical smears suggestive of high-grade lesions (median, 4,425,883 copies/ micro g of DNA) than in women with normal smears (median, 54,576), controlling for age (P = 0.006).

Base Sequence↗
PubMed2003

Molecular analysis of human papillomavirus type 52 isolates detected in the genital tract of human immunodeficiency virus-seropositive and -seronegative women.

Human papillomavirus (HPV) type 52 DNA was detected in cervicovaginal lavage samples from 91 (12.4%) of 732 human immunodeficiency virus (HIV)-seropositive women and 23 (7.1%) of 323 HIV-seronegative women (P=.0004). HIV infection was an independent predictor for HPV-52 infection when controlling for age and sexual activity (odds ratio, 2.21; 95% confidence interval, 1.30-3.75: P=.003). We describe the genomic polymorphism of 114 HPV-52 isolates. Long control region (LCR) mutations defined 27 HPV-52 variants. Nearly 32% of HPV-52 isolates carried deletions in the LCR. E6 and E7 mutations defined 17 and 9 variants, respectively. Five nonsynonymous E6 mutations were clustered from amino acids 92 to 94, near the putative p53 binding area. White women were more frequently infected by the prototype strain than were women of African descent (P=.0001). The genetic diversity of HPV-52 should facilitate the investigation of the role of genomic variations in cervical disease.

Adult↗
PubMed2003

Human papillomavirus and HIV coinfection and the risk of neoplasias of the lower genital tract: a review of recent developments.

One of the risk factors for human papillomavirus (HPV) infection and subsequent lower genital tract neoplasias and cancers is impaired cell-mediated immunity. HIV-positive women with severe immunosuppression are 5 times more likely than HIV-negative women to have lower genital tract neoplasias. A corresponding increase in the risk of invasive vulvar and anal cancers, but not of cervical cancer, has also been observed among HIV-positive women. Treatment failure and recurrence of neoplasia occur much more frequently among HIV-positive than among HIV-negative women. In this review, we discuss recent advances in the understanding of the relation between HIV and HPV coinfection and the development of lower genital tract neoplasias and cancers in women. In addition, we present strategies for monitoring and treating noninvasive and invasive neoplasias of the lower genital tract in HIV-positive women.

Anus Neoplasms↗