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Biomedical subjects

L Denny

Publications and source records attributed to L Denny.

At least 19 recordsLinked to original sources

Media interventions to increase cervical screening uptake in South Africa: an evaluation study of effectiveness.

Successful cervical cancer prevention depends on reaching, screening and treating women with pre-invasive disease. We aimed to evaluate the effectiveness of two media interventions-a photo-comic and a radio-drama-in increasing cervical screening uptake. A randomized controlled trial compared a photo-comic on cervical cancer screening with a placebo comic. One month after the comics were distributed a radio-drama paralleling the photo-comic was broadcast on the community radio station and a retrospective evaluation was carried out. The trial was set in Khayelitsha, a peri-urban squatter community near Cape Town, South Africa. A random sample consisted of 658 women between the ages of 35 and 65 years, from a stratified sample of census areas. The main outcome measure was self-reported cervical screening uptake 6 months after distribution of the comics. Seven percent (18 of 269) of women who received the intervention photo-comic reported cervical screening during the 6 months follow-up, compared with 6% (25 of 389) of controls (P = 0.89). Women who recalled hearing the radio-drama were more likely to report attending screening (nine of 53, 17%) than those who did not (19 of 429, 4%; P < 0.001). We conclude that the photo-comic was ineffective in increasing cervical screening uptake in this population. The radio-drama may have had more impact, but only a minority of women recalled being exposed to it. Future research must concentrate not only on achieving high level of exposure to health messages, but also on investigating the links between exposure and action.

Adult↗

Limited Pap screening associated with reduced risk of cervical cancer in South Africa.

BACKGROUND: We investigated the effect of Pap smear screening on the incidence of invasive cancer of the cervix in the Western Cape, South Africa where screening is limited. METHODS: Data were derived from a case-control study of the association of hormonal contraceptives and invasive cervical cancer. Incident cases (n = 524) of invasive cervical cancer who presented at two tertiary hospitals and controls (n = 1540) series matched for age, race, and place of residence were interviewed. Information on a wide range of variables was collected including whether the women had previously had a Pap smear taken and the number and timing of smears. Odds ratios (OR) and 95% CI were calculated using multiple logistic regression. RESULTS: The OR of cervical cancer was reduced among women who had ever had a smear (OR = 0.3, 95% CI: 0.3-0.4). The OR declined with increasing number of smears to 0.2 for >/=>3 smears (trend P = 0.0003). Among women who had a smear <5 years previously the OR was 0.3, but even if the smear was taken >/=15 years previously the women remained at reduced risk (OR = 0.5). CONCLUSION: The data suggest that even limited Pap smear screening reduces the risk of cervical cancer. Should a screening programme be successfully implemented, the incidence of cervical cancer might be reduced by as much as 70%.

Adult↗

Policy analysis of cervical cancer screening strategies in low-resource settings: clinical benefits and cost-effectiveness.

CONTEXT: Cervical cancer is a leading cause of cancer-related death among women in developing countries. In such low-resource settings, cytology-based screening is difficult to implement, and less complex strategies may offer additional options. OBJECTIVE: To assess the cost-effectiveness of several cervical cancer screening strategies using population-specific data. DESIGN AND SETTING: Cost-effectiveness analysis using a mathematical model and a hypothetical cohort of previously unscreened 30-year-old black South African women. Screening tests included direct visual inspection (DVI) of the cervix, cytologic methods, and testing for high-risk types of human papillomavirus (HPV) DNA. Strategies differed by number of clinical visits, screening frequency, and response to a positive test result. Data sources included a South African screening study, national surveys and fee schedules, and published literature. MAIN OUTCOME MEASURES: Years of life saved (YLS), lifetime costs in US dollars, and incremental cost-effectiveness ratios (cost per YLS). RESULTS: When analyzing all strategies performed as a single lifetime screen at age 35 years compared with no screening, HPV testing followed by treatment of screen-positive women at a second visit, cost $39/YLS (27% cancer incidence reduction); DVI, coupled with immediate treatment of screen-positive women at the first visit was next most effective (26% cancer incidence reduction) and was cost saving; cytology, followed by treatment of screen-positive women at a second visit was least effective (19% cancer incidence reduction) at a cost of $81/YLS. For any given screening frequency, when strategies were compared incrementally, HPV DNA testing generally was more effective but also more costly than DVI, and always was more effective and less costly than cytology. When comparing all strategies simultaneously across screening frequencies, DVI was the nondominated strategy up to a frequency of every 3 years (incremental cost-effectiveness ratio, $460/YLS), and HPV testing every 3 years (incremental cost-effectiveness ratio, $11 500/YLS) was the most effective strategy. CONCLUSION: Cervical cancer screening strategies that incorporate DVI or HPV DNA testing and eliminate colposcopy may offer attractive alternatives to cytology-based screening programs in low-resource settings.

Adult↗

Oral antibodies to human papillomavirus type 16 in women with cervical neoplasia.

This study investigated the relationship between human papillomavirus type 16 (HPV-16) antibodies detected in oral fluid from women with cervical neoplasia, their HPV-16 antibody seroprevalence, and their cervical HPV-16 DNA presence. Cervical HPV-16 DNA was detected by polymerase chain reaction in 43.2% (35/81) of these women. The prevalence of IgG and IgA antibodies to HPV-16 virus-like particles (VLP-16) in oral fluid and was investigated by enzyme-linked immunosorbent assay. Anti-VLP-16 IgA antibodies were detected in oral fluid from 54.3% (44/81) of women with cervical neoplasia, compared with 8% (3/36) in controls (P = 0.000002). Anti-VLP-16 IgG was detected in oral fluid from 43.2.9% (25/72) and 13.3% (4/30; P = 0.029), respectively. Women who were HPV-16 DNA positive at their cervical lesion, displayed an oral fluid anti-VLP-16 IgA prevalence of 60.7% (17/28) and HPV-16 DNA negative women an oral fluid anti-VLP-16 IgA prevalence of 50% (20/40; P = 0.38). Oral fluid anti-VLP-16 IgG prevalence in HPV-16 DNA positive women was 28.6% (8/28) compared with 40% (16/40) in oral fluid from HPV-16 DNA negative women (P = 0.3). Amongst HPV-16 DNA positive women, the anti-VLP-16 IgG seroprevalence was 75% (21/28) and IgA seroprevalence 35.7% (10/28) and for the HPV-16 DNA negative women these values were 60% (24/40) and 32.5% (13/40), respectively. Oral IgA antibody testing proved no more sensitive than serum antibody detection for the determination of HPV infection but could be useful as a non-invasive screening method for women with cervical neoplasia and for estimating the mucosal antibody response to HPV vaccines.

Adolescent↗

Evaluation of alternative methods of cervical cancer screening for resource-poor settings.

BACKGROUND: Noncytologic methods of screening for cervical carcinoma and its precursor lesions are needed for resource-poor settings in which cervical carcinoma continues to be an important cause of morbidity and mortality. METHODS: Two thousand nine hundred forty-four women ages 35-65 years were recruited from Cape Town, South Africa and screened using a combination of a Papanicolaou (Pap) smear, human papillomavirus (HPV) DNA testing, direct visual inspection after the application of a 5% acetic acid solution (DVI), and cervicography. Cervicography was considered primarily as a method with which to quality control the DVI examinations. Women with squamous intraepithelial lesions (SIL) or carcinoma on Pap smear, positive DVI examination (acetowhite lesion or cervical ulcer/growth), high levels of high risk HPV DNA (relative light units [RLU] > 10x positive control), or positive Cervigramtrade mark were referred for colposcopy and cervical biopsy. RESULTS: Pap smears were positive in 8.1% of all women screened and identified 65 (78%) of all cases of biopsy confirmed high grade disease (high grade SIL or invasive carcinoma). DVI and cervicography were classified as positive in 18.1% and 10.5%, respectively, of women screened and identified 58 (67%) and 46 (58%) of all cases of high grade disease, respectively. The results of HPV DNA testing varied depending on the cutoff value used to define a positive result. At the standard cutoff level (RLU > 1x positive control), 16.2% of women screened were classified as high risk HPV DNA positive, as were 63 women with high grade disease (73%). CONCLUSIONS: DVI and HPV DNA testing identified similar numbers of high grade SIL (cervical intraepithelial neoplasia Grade 2,3) and invasive carcinoma cases as Pap smears. However, both classify considerably more women without cervical disease as being test positive.

Adult↗

Human papillomavirus DNA testing for cervical cancer screening in low-resource settings.

BACKGROUND: In many low-resource settings, there are barriers to cytologic screening for cervical cancer. This study evaluates human papillomavirus (HPV) DNA testing as an alternative screening method. METHODS: Cervical samples from 2944 previously unscreened South African women aged 35-65 years were tested for high-risk types of HPV with the use of the Hybrid Capture I (HCI) assay. Women also had a Pap smear, direct visual inspection of the cervix, and Cervicography(TM). Women positive on any screening test were referred for colposcopy. Samples from women with biopsy-confirmed, low-grade squamous intraepithelial lesions (SILs) (n = 95), high-grade SILs (n = 74), or invasive cervical cancer (n = 12) and a random sample of women with no cervical disease (n = 243) were retested for HPV DNA with the use of the more sensitive Hybrid Capture II (HCII) assay. All P values are two-sided. RESULTS: High-risk HPV DNA was detected in 73.3% and 88.4% of 86 women with high-grade SIL or invasive cancer and in 12.2% of 2680 and 18.1% of 243 women without evidence of cervical disease, with the use of the HCI and HCII assays, respectively. HPV DNA testing with the HCII assay was more sensitive than cytology for detecting high-grade SIL and invasive cancer (McNemar's test, P =.04), and testing with the HCI assay was of equivalent sensitivity (P =.61). Cytology had a statistically significantly better specificity (96.8%) than either the HCI assay (87.8%) or the HCII assay (81.9%) (P<.01). Receiver operating characteristic curves identified test cutoff values that allow HPV DNA testing to identify 57% of women with high-grade SIL or cancer, while classifying less than 5% of women with no cervical disease as HPV DNA positive. CONCLUSIONS: HPV DNA testing has a sensitivity equivalent to, or better than, that of cytology. Since HPV DNA testing programs may be easier to implement than cytologic screening, HPV testing should be considered for primary cervical cancer screening in low-resource settings.

Adult↗

HPV DNA testing of self-collected vaginal samples compared with cytologic screening to detect cervical cancer.

CONTEXT: More than half of the women diagnosed as having cervical cancer in the United States have not been screened within the last 3 years, despite many having had contact with the health care system. In many other regions of the world, there is only limited access to cervical cancer screening. OBJECTIVE: To determine whether testing of self-collected vaginal swabs for human papillomavirus (HPV) DNA can be used to screen for cervical disease in women aged 35 years and older. DESIGN: Cross-sectional observational study comparing Papanicolaou smears with HPV DNA testing of self-collected vaginal swabs. SETTING: Outpatient clinics in a periurban settlement outside of Cape Town, South Africa, between January 1998 and April 1999. PARTICIPANTS: Screening was performed on 1415 previously unscreened black South African women aged 35 to 65 years. INTERVENTION: Women self-collected a vaginal swab for HPV testing in the clinic and were then screened using 4 different tests: Papanicolaou smear, direct visual inspection of the cervix after the application of 5% acetic acid, cervicography, and HPV DNA testing of a clinician-obtained cervical sample. Women with abnormal results on any of the screening tests were referred for colposcopy. MAIN OUTCOME MEASURE: Biopsy-confirmed high-grade cervical squamous intraepithelial lesions or invasive cancer. RESULTS: High-grade squamous intraepithelial lesions were identified in 47 (3.4%) of 1365 women adequately assessed, and there were 9 cases of invasive cancer. Of women with high-grade disease, 66.1% (95% confidence interval [CI], 52.1%-77.8%) had high risk for HPV detected in self-collected vaginal samples, and 67.9% (95% CI, 53.9%-79.4%) had an abnormal Papanicolaou smear (P = .78). The false-positive rates for HPV DNA testing of self-collected vaginal samples and Papanicolaou smears were 17.1% (95% CI, 15.1%-19.3%) and 12.3% (95% CI, 10.5%-14.2%), respectively (P<.001). A high-risk type of HPV DNA was detected in 83.9% (95% CI, 71.2%-91.9%) of women with high-grade disease and 15.5% (95% CI, 13.6%-17.7%) of women with no evidence of cervical disease using a clinician-obtained cervical sample. CONCLUSIONS: These results indicate that HPV testing of self-collected vaginal swabs is less specific than but as sensitive as Papanicolaou smears for detecting high-grade cervical disease in women aged 35 years and older, and HPV testing offers an important new way to increase screening in settings where cytology is not readily performed.

Adult↗

Seroresponses to human papillomavirus types 16, 18, 31, 33, and 45 virus-like particles in South African women with cervical cancer and cervical intraepithelial neoplasia.

The aim of the study was to determine the prevalence of antibodies to human papillomavirus (HPV) types 16, 18, 31, 33, and 45 in woman in Cape Town with cervical intraepithelial neoplasia (CIN) (n = 95), cervical cancer (n = 40), female blood donors (n = 95) and children (n = 110). The enzyme-linked immunosorbent assay (ELISA) made use of baculovirus synthesised HPV virus like particles (VLPs) as antigen. Antibodies to at least one HPV type were detected in sera from 75% of cancer patients, 71.6% of CIN patients, 44.2% of blood donors and 27.3% of children. Sera from 95 women with CIN were compared with age-matched female blood donors. There was a significant association of seropositivity to VLP-16 (P = 0.006) and VLP-45 (P = 0.008) with CIN compared with the blood donors. There was also a significant difference in the seropositivity of women with CIN to any of the five virus-like particle (VLP) types compared to the blood donors (P = 0.0002: OR = 3.2). Thirty-nine of sixty-nine (56.5%) women with CIN were found to be HPV-16 DNA positive. The average age of women in this group that were VLP-16 seropositive was 34 years and those found to be VLP-16 seronegative was 52 years of age. Antibodies to all five VLP types were detected in these populations, thus an ideal vaccine should induce protection from infection by a wide range of HPV types.

Adult↗

Two-stage cervical cancer screening: an alternative for resource-poor settings.

OBJECTIVE: We sought to introduce 2-stage cervical cancer screening in which 2 screening tests are performed sequentially (the second test is performed only if the first result is positive), followed by treatment if both test results are abnormal. STUDY DESIGN: A total of 1423 women from Cape Town, South Africa, were screened by direct visual inspection, human papillomavirus deoxyribonucleic acid testing, cytologic testing, and cervicography. If an abnormality was identified with any test, women were referred for colposcopy. RESULTS: Direct visual inspection, cytologic testing, human papillomavirus deoxyribonucleic acid testing, and cervicography, when used alone, identified 24, 26, 23, and 23 cases of disease (high-grade squamous intraepithelial lesion or cancer) per 1000 women, respectively, and would classify 182, 71, 137, and 112 women without disease as having abnormal results. Two-stage screening with direct visual inspection first, followed by cytologic testing, human papillomavirus deoxyribonucleic acid testing, or cervicography, would detect 18, 16, and 18 cases per 1000 women, respectively, and would substantially reduce the number of women without disease who were classified as having abnormal results. CONCLUSION: Two-stage screening for cervical cancer provides an attractive alternative to conventional screening for low-resource settings.

Adult↗

Prevalence of visible disruption of cervical epithelium and cervical ectopy in African women using Depo-Provera.

Associations between Depo-Provera (injectable, progesterone-only contraceptive) use and visible disruption of cervical epithelium and cervical ectopy were investigated using data collected as part of a cervical cancer screening study in periurban Cape Town, South Africa. Women were interviewed about their contraceptive use, and underwent a gynecologic examination that included two 35-mm photographs of the cervix after application of 5% acetic acid. Photographs of 723 subjects were reviewed (blind to clinical information and using systematic criteria developed before review) for evidence of atrophy and epithelial disruption, including inflammation and ulceration. The percentage of the cervix covered with columnar epithelium (ectopy) was also estimated from the photographs. A random sample of 85 photographs was reviewed again for reliability. A total of 121 current users of Depo-Provera were no more likely to have evidence of epithelial disruption (38%) than 574 nonusers (39%), odds ratio (OR) = 1.37, 95% CI: 0.89-2.11 adjusting for age and parity. The prevalence of significant ectopy (columnar epithelium covering > 10% of the cervix) was also no different among current Depo-Provera users (OR = 1.22, 95% CI: 0.80-1.86 adjusting for age and parity). Reliability of visual scoring of epithelial disruption and ectopy was excellent (kappa = 0.8). Although the underlying prevalence of visible disruption of cervical epithelium was very high, current use of Depo-Provera was not associated with increased prevalence of visible disruption of the cervical epithelium or with ectopy in this sample of African women.

Adult↗

Effects of morphine and tramadol on somatic and visceral sensory function and gastrointestinal motility after abdominal surgery.

BACKGROUND: Chronic nociceptive input induces sensitization and changes in regulatory reflexes in animal models. In humans, postoperative somatic and visceral sensitization and the secondary effects on reflex gut motility are unclear. METHODS: Somatic and visceral sensation and gastrointestinal motility were evaluated after abdominal hysterectomies in 50 patients who were randomized to receive double-blinded postoperative 48-h infusions of morphine or tramadol. Pain scores, rectal distension, skin electric sensation and pain tolerance thresholds, and gastrointestinal transit were assessed before and after operation, during and after analgesic infusions. RESULTS: Pain intensity scores decreased similarly with morphine and tramadol infusions (total doses, 66.8+/-20 mg and 732.4+/-152 mg [mean +/- SD], respectively). Skin pain tolerance thresholds in the incisional dermatome remained similar with morphine and tramadol throughout the study. During morphine infusions, pain tolerance thresholds on the shoulder increased (P<0.05) and then decreased after discontinuation on day 4 (P<0.02) compared with before operation. Rectal distension pain tolerance pressure thresholds increased after operation during morphine infusions (P<0.05). Similar but nonsignificant trends occurred with tramadol. Orocecal and colonic transit times increased after operation with both morphine and tramadol (P<0.005), but gastric emptying was prolonged only with morphine (P = 0.03). AU motility and sensory parameters had returned to preoperative levels by 1 month after operation. CONCLUSIONS: Pain control was equally effective with morphine and tramadol infusions. No somatic or visceral sensitization was evident during morphine and tramadol infusions, but pain tolerance thresholds as markers of antinociception were increased more during morphine infusions. The significant sensitization seen only after morphine discontinuation may be due to convergent visceral input. Gut motility was prolonged significantly by visceral surgery itself and also by morphine.

Adult↗

Acetic acid visualization of the cervix: an alternative to cytologic screening.

OBJECTIVE: To investigate the value of acetic acid visualization of the cervix as an alternative to cytologic screening. METHODS: A prospective study was conducted in a squatter area in Cape Town, South Africa, on 2426 women who underwent speculum examination, naked-eye inspection of the cervix after application of acetic acid, and cytologic smear. The smears were stained and processed at the screening site. Patients with a positive reading after acetic acid or a smear indicating a high-grade squamous intraepithelial lesion (SIL) were referred for immediate colposcopy, biopsy, and when indicated, treatment by large loop excision of the transformation zone. Therefore, histology was obtained on all patients with a positive acetic acid test or a positive cytology. RESULTS: Seventy-six women with positive reactions to acetic acid. Among the 2350 women with negative reactions, 254 had positive cervical smears; only 11 of these had histologic high-grade SIL. In contrast, 20 of the 61 women with positive cytology and positive acetic acid test had high-grade SIL on histology. Therefore, the acetic acid reaction enabled the observer to detect 20 of the 31 women (64%) who exhibited a high-grade SIL both on cytology and histology. CONCLUSION: In locations where access to cytopathology is limited, naked-eye visualization of the cervix after application of diluted acetic acid warrants consideration as an alternative in the detection of cervical premalignant lesions.

Acetates↗