Alliance for cervical cancer prevention: setting the record straight.
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Developing Countries↗
Biomedical subjects
Lynette Denny
Publications and source records attributed to Lynette Denny.
Recurrence of symptomatic bacterial vaginosis 12 months after oral metronidazole therapy in HIV-positive and -negative women.
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Administration, Oral↗
Prospective study of hormonal contraception and women's risk of HIV infection in South Africa.
BACKGROUND: Many women using hormonal contraceptives are also at risk of sexually transmitted HIV infection, but data are mixed on whether hormonal contraception increases women's risk of HIV. We investigated associations between HIV incidence and use of combined oral contraceptives (COC), norethindrone enanthate (NET-EN) or depot medroxyprogesterone acetate (DMPA) in a cohort of South African women. METHODS: Participants were 4200 HIV-negative women aged 35-49 years enrolled into a cervical cancer screening trial. At enrollment, women were tested for sexually transmitted infections and reported on their sexual behaviour and contraceptive use. During the 24 months of follow-up, women reported on their sexual behaviours and contraceptive use and underwent repeat HIV testing. RESULTS: During the 5010 person-years of follow-up, 111 incident HIV infections were observed (HIV incidence, 2.2 infections/100 person-years). At enrollment, 21% of women reported using hormonal contraception, primarily DMPA (14% of all women) or NET-EN (5%). After adjusting for sexual risk behaviours and sexually transmitted infections, the incidence of HIV was similar among women using COC, NET-EN or DMPA compared with women not using any hormonal method [incidence rate ratios and 95% confidence intervals, 0.65, 0.16-2.66; 0.79, 0.31-2.02 and 0.96, 0.58-1.59, respectively]. There was also no association between increased duration of DMPA use and HIV incidence (P-value for trend, 0.51). CONCLUSIONS: These findings contribute to the evidence from general population cohorts of women that hormonal contraceptive use is not associated with increased risk of HIV acquisition. Nonetheless, family planning services are an important venue for HIV prevention activities.
Adult↗
Chapter 8: Screening for cervical cancer in developing countries.
Organised and quality assured cytology-based screening programmes have substantially reduced cervical cancer incidence in many developed countries. However, there are considerable barriers to setting up cytology-based screening programs, particularly in developing countries. This has stimulated the search for novel and alternative approaches to cytology for cervical cancer prevention. These approaches generally perform as well as cytology, and sometimes better, although many of them have a lower specificity, resulting in higher false-positive rates. The possibility of linking screening to treatment in a one- or two-visit strategy appears to be safe, feasible and effective. Barriers to establishing screening programs and the pitfalls encountered differ from one country to the next. Country-specific solutions need to be found, while being cognizant of the criteria that have enabled successful screening programmes.
Developing Countries↗
More men than women make mucosal IgA antibodies to Human papillomavirus type 16 (HPV-16) and HPV-18: a study of oral HPV and oral HPV antibodies in a normal healthy population.
BACKGROUND: We have previously shown the high prevalence of oral anti-human papillomavirus type 16 (HPV-16) antibodies in women with HPV-associated cervical neoplasia. It was postulated that the HPV antibodies were initiated after HPV antigenic stimulation at the cervix via the common mucosal immune system. The present study aimed to further evaluate the effectiveness of oral fluid testing for detecting the mucosal humoral response to HPV infection and to advance our limited understanding of the immune response to HPV. METHODS: The prevalence of oral HPV infection and oral antibodies to HPV types 16, 18 and 11 was determined in a normal, healthy population of children, adolescents and adults, both male and female, attending a dental clinic. HPV types in buccal cells were determined by DNA sequencing. Oral fluid was collected from the gingival crevice of the mouth by the OraSure method. HPV-16, HPV-18 and HPV-11 antibodies in oral fluid were detected by virus-like particle-based enzyme-linked immunosorbent assay. As a reference group 44 women with cervical neoplasia were included in the study. RESULTS: Oral HPV infection was highest in children (9/114, 7.9%), followed by adolescents (4/78, 5.1%), and lowest in normal adults (4/116, 3.5%). The predominant HPV type found was HPV-13 (7/22, 31.8%) followed by HPV-32 (5/22, 22.7%). The prevalence of oral antibodies to HPV-16, HPV-18 and HPV-11 was low in children and increased substantially in adolescents and normal adults. Oral HPV-16 IgA was significantly more prevalent in women with cervical neoplasia (30/44, 68.2%) than the women from the dental clinic (18/69, 26.1% P = 0.0001). Significantly more adult men than women displayed oral HPV-16 IgA (30/47 compared with 18/69, OR 5.0, 95% CI 2.09-12.1, P < 0.001) and HPV-18 IgA (17/47 compared with 13/69, OR 2.4, 95% CI 0.97-6.2, P = 0.04). CONCLUSION: The increased prevalence of oral HPV antibodies in adolescent individuals compared with children was attributed to the onset of sexual activity. The increased prevalence of oral anti-HPV IgA in men compared with women was noteworthy considering reportedly fewer men than women make serum antibodies, and warrants further investigation.
Antibodies, Viral↗
Direct comparison of liquid-based and conventional cytology in a South African screening trial.
Our study directly compares the performance of liquid-based (LBC) and conventional cytology for detecting high-grade cervical intraepithelial neoplasia and cancer (CIN 2+) in high-risk, previously unscreened women. As part of a larger randomized clinical trial assessing the efficacy and safety of a "screen and treat" program for cervical cancer prevention, 5,652 South African women, aged 35 to 65 years, were screened using either ThinPrep or conventional Papanicolaou cytology. The cytology method used (i.e., ThinPrep or conventional) was rotated on a 6-month basis for the duration of the study. Directly following collection of the cytology specimen, all women underwent colposcopy with endocervical curettage and biopsy of all colposcopic abnormalities. Assessment of cytology and histology results was blinded and results were compared using histology-confirmed CIN as the "gold standard." The accuracy of LBC and conventional cytology was statistically equivalent, although the sensitivity of conventional cytology was at least 5 percentage points higher at all cutoff levels. For example, at a cytology cutoff level of low-grade squamous intraepithelial lesion, the sensitivity of LBC was 60.3% for CIN2+ vs. 69.1% for conventional cytology and specificity was 94.1% and 94.5%, respectively. LBC specimens were significantly less likely to be "satisfactory-but-limited-by" (6.5% vs. 27.9%) but significantly more likely to be unsatisfactory (2.2% vs. 0.8%). Thus, in this high-risk population, the sensitivity of LBC is no greater than the sensitivity of conventional cytology. Because of the higher unit cost of LBC, low resource settings should carefully consider the potential benefits and drawbacks of LBC before adopting this new technology.
Adult↗
Distinguishing the temporal association between women's intravaginal practices and risk of human immunodeficiency virus infection: a prospective study of South African women.
Cross-sectional studies have suggested that intravaginal practices, such as douching or "dry sex," may increase women's susceptibility to infection with human immunodeficiency virus (HIV). The authors examined the temporal nature of this association in a cohort of South African women. At enrollment (2001-2002), 4,089 women were tested for HIV infection. Participants reported their intravaginal practices at a 6-month follow-up visit and were followed with repeat HIV testing for up to 24 months. Among the 3,570 women who were HIV-negative at enrollment, 26% reported some type of intravaginal practice, mostly washing inside the vagina with water and/or cloth as part of daily hygiene. During follow-up, 85 incident HIV infections were observed. Intravaginal practices were associated with prevalent HIV at enrollment (adjusted odds ratio = 1.50, 95% confidence interval: 1.22, 1.85), but during follow-up there was no association between intravaginal practices and incident HIV (adjusted hazard ratio = 1.04, 95% confidence interval: 0.65, 1.68). These findings may be explained by a reversal of the causal sequence assumed for this association, since intravaginal practices may be undertaken in response to vaginal infections that occur more commonly among HIV-infected women. Intravaginal practices appear unlikely to be a cofactor in the male-to-female transmission of HIV in this setting.
Adult↗
Nested case-control study of cervical mucosal lesions, ectopy, and incident HIV infection among women in Cape Town, South Africa.
OBJECTIVE: The objective of this study was to test whether cervical mucosal lesions and ectopy increase women's susceptibility to HIV infection. STUDY DESIGN: HIV-seronegative women ages 35 to 65 years (n = 5773) enrolled into a cervical cancer screening trial were followed for up to 36 months. All HIV seroconverters (n = 86) in the cohort were compared with randomly selected controls (n = 324) who did not seroconvert. Magnified photographs of the cervix taken during speculum examination at enrollment were evaluated for cervical mucosal lesions and ectopy using standard criteria. RESULTS: The presence of mucosal lesions (observed among 19% of controls) was associated with increased risk of HIV seroconversion (adjusted odds ratio [AOR] = 1.93; 95% confidence interval [CI] = 1.07-3.48). Ectopy extending over >20% of the cervix was also associated with HIV seroconversion (AOR = 2.18; 95% CI = 1.01-4.69). CONCLUSIONS: Visible lesions of cervical mucosa and cervical ectopy may be markers of increased susceptibility to HIV infection among women. Protection of the mucosa of the cervix may provide an important approach for new HIV prevention technologies.
Adult↗
The agreement between cervical abnormalities identified by cytology and detection of high-risk types of human papillomavirus.
OBJECTIVES AND DESIGN: Human papillomavirus (HPV) is causally associated with cervical cancer. Using the Digene Hybrid Capture 2 high-risk HPV test (HC2), we investigated the prevalence of high-risk HPV in cervical specimens, and compared results with those of Papanicolaou (Pap) smears taken concurrently. SUBJECTS AND SETTING: Cervical specimens were obtained from women attending hospitals / community health centres in the Western Cape province of South Africa. They were participating in a case-control study of the association of hormonal contraceptives and invasive cervical cancer. RESULTS: Of 1 491 women tested, 254 (17%) were HPV DNA positive. The age-specific prevalence of HPV was 36/97 (37.1%) in those aged < 30 years, 78/369 (21.1%) in those aged 30 - 39 years, 78/603 (12.9%) in those aged 40 - 49 years and 62/422 (14.7%) in those aged 50 - 59 years. In women with normal cytology the prevalence of HPV was 10.9% (138/1 264); in those with abnormal squamous cells of unknown significance (AS-CUS) it was 30.8% (36/117); in those with low-grade squamous intraepithelial lesions (LSIL) it was 63.2% (36/57), and in those with high-grade squamous intraepithelial lesions (HSIL) it was 83% (44/53). The odds ratio between HPV and HSIL in women aged 40 - 59 years was 57.1 (confidence interval 22.4 - 170.7). CONCLUSIONS: HC2 detected a high prevalence of HPV (17%) in this population. Most women with HSIL (83%) were positive, indicating that HPV testing of AS-CUS women may aid in management. When costs decrease, HC2 could be introduced as an adjunct to Pap smears in identifying women at risk for high-grade cervical disease and could be useful in the maintenance of cervical health in those who remain Pap smear negative.
Adult↗
Screen-and-treat approaches for cervical cancer prevention in low-resource settings: a randomized controlled trial.
CONTEXT: Non-cytology-based screen-and-treat approaches for cervical cancer prevention have been developed for low-resource settings, but few have directly addressed efficacy. OBJECTIVE: To determine the safety and efficacy of 2 screen-and-treat approaches for cervical cancer prevention that were designed to be more resource-appropriate than conventional cytology-based screening programs. DESIGN, SETTING, AND PATIENTS: Randomized clinical trial of 6555 nonpregnant women, aged 35 to 65 years, recruited through community outreach and conducted between June 2000 and December 2002 at ambulatory women's health clinics in Khayelitsha, South Africa. INTERVENTIONS: All patients were screened using human papillomavirus (HPV) DNA testing and visual inspection with acetic acid (VIA). Women were subsequently randomized to 1 of 3 groups: cryotherapy if she had a positive HPV DNA test result; cryotherapy if she had a positive VIA test result; or to delayed evaluation. MAIN OUTCOME MEASURES: Biopsy-confirmed high-grade cervical cancer precursor lesions and cancer at 6 and 12 months in the HPV DNA and VIA groups compared with the delayed evaluation (control) group; complications after cryotherapy. RESULTS: The prevalence of high-grade cervical intraepithelial neoplasia and cancer (CIN 2+) was significantly lower in the 2 screen-and-treat groups at 6 months after randomization than in the delayed evaluation group. At 6 months, CIN 2+ was diagnosed in 0.80% (95% confidence interval [CI], 0.40%-1.20%) of the women in the HPV DNA group and 2.23% (95% CI, 1.57%-2.89%) in the VIA group compared with 3.55% (95% CI, 2.71%-4.39%) in the delayed evaluation group (P<.001 and P = .02 for the HPV DNA and VIA groups, respectively). A subset of women underwent a second colposcopy 12 months after enrollment. At 12 months the cumulative detection of CIN 2+ among women in the HPV DNA group was 1.42% (95% CI, 0.88%-1.97%), 2.91% (95% CI, 2.12%-3.69%) in the VIA group, and 5.41% (95% CI, 4.32%-6.50%) in the delayed evaluation group. Although minor complaints, such as discharge and bleeding, were common after cryotherapy, major complications were rare. CONCLUSION: Both screen-and-treat approaches are safe and result in a lower prevalence of high-grade cervical cancer precursor lesions compared with delayed evaluation at both 6 and 12 months. Trial Registration http://clinicaltrials.gov Identifier: NCT00233727.
Acetic Acid↗
Bacterial vaginosis and susceptibility to HIV infection in South African women: a nested case-control study.
BACKGROUND: Bacterial vaginosis (BV) may increase women's susceptibility to HIV infection, but there are few prospective data. METHODS: During follow-up for up to 36 months, 86 new HIV seroconverters (case patients) were identified among 5110 women enrolled in a cervical cancer screening trial. Nonseroconverting control subjects (n=324) were frequency matched to case patients by age and duration of follow-up. At enrollment, case patients and control subjects were evaluated for clinical signs of BV, and Gram stains of vaginal fluid were scored using Nugent criteria. RESULTS: BV was diagnosed on the basis of clinical criteria at enrollment in 20% of seroconverters and 16% of control subjects (summary odds ratio [OR], 1.31 [95% confidence interval {CI}, 0.71-2.41]). Nugent criteria for BV were met by 74% of seroconverters and 62% of control subjects. Diagnosis of BV on the basis of Nugent criteria was significantly associated with an increased risk of HIV seroconversion, after adjustment for demographic characteristics, other sexually transmitted infections, and sexual behaviors (adjusted OR, 2.01 [95% CI, 1.12-3.62]). CONCLUSIONS: BV may account for a substantial fraction of new HIV infections in this setting. Treatment of BV and other interventions to promote normal vaginal flora warrant attention for HIV prevention.
Adult↗
Detection of HPV 16 and HPV 18 DNA in the blood of patients with cervical cancer.
Persistent infection of the uterine cervix with high-risk human papillomaviruses (HPV) is causally associated with cancer of the cervix. A few studies have reported the presence of HPV DNA in the blood of women with cervical neoplasia. The aim of this study was to determine if HPV DNA could be detected in whole blood of women with a range of cervical pathologies and with HPV 16 or 18 cervical infections and if there is a correlation between cervical lesion grade and the appearance of HPV DNA in the circulatory system. Forty-five women with histologically graded cervical cancer were confirmed to have cervical HPV 16 or 18 infections. Eleven (24.4%) of these women had detectable HPV 16 or 18 in their blood. The HPV types detected in the blood matched those detected at the cervix. No HPV 16 or 18 DNA was detected in the blood of 32 women with pre-cursor cervical lesions or normal cervical pathology but who had cervical HPV 16 or 18 infections. One of 77 women with normal cervical pathology and no cervical HPV infection was positive for HPV 16 DNA in her blood. The results indicate that HPV DNA can be detected in the blood of women with more advanced cervical carcinomas but not in the blood of women with pre-cursor cervical lesions. The results of our study indicate that the role of HPV DNA in the circulatory system appears not be of diagnostic significance and HPV DNA is only detectable in women with more advanced cervical cancers.
Adult↗
Management of cervical disease in HIV-infected women.
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Adolescent↗
Intravaginal practices, bacterial vaginosis, and women's susceptibility to HIV infection: epidemiological evidence and biological mechanisms.
Intravaginal practices such as "dry sex" and douching have been suggested as a risk factor that may increase women's susceptibility to HIV infection. These behaviours appear common in different populations across sub-Saharan Africa, where practices include the use of antiseptic preparations, traditional medicines, or the insertion of fingers or cloths into the vagina. We systematically review the evidence for the association between women's intravaginal practices and HIV infection. Although a number of cross-sectional studies have shown that prevalent HIV infection is more common among women reporting intravaginal practices, the temporal nature of this association is unclear. Current evidence suggests that bacterial vaginosis, which is a likely risk factor for HIV infection, may be a mediator of the association between intravaginal practices and HIV. Although biologically plausible mechanisms exist, there is currently little epidemiological evidence suggesting that intravaginal practices increase women's susceptibility to HIV infection. Further research into factors that increase women's susceptibility to HIV will help to inform the design of vaginal microbicides and other HIV prevention interventions.
Disease Susceptibility↗
The prevention of cervical cancer in developing countries.
Cervical cancer remains the commonest cancer cause of death among women in developing countries, largely due to the failure to establish cytologically based cervical cancer screening programmes. There are many barriers to the establishment of screening programmes in poor countries ranging from limited financial, human and health resources to the complex infrastructural requirements of traditional screening programmes. Alternative approaches to cervical cancer prevention are currently being investigated, including primary prevention with prophylactic vaccines against human papillomavirus to alternative screening tests and protocols. These will be explored in this review.
Adult↗
Widening the cervical cancer screening net in a South African township: who are the underserved?
Cervical cancer screening services in South Africa have failed to reach the majority of the population and to significantly reduce mortality. A household survey in a predominantly Black African population living in a low-income township on the outskirts of Cape Town was undertaken to ascertain the characteristics of women reporting never having been screened. In our group of 664 representatively sampled women. 45% of women reported having had a cervical screening test. However, in what at first glance appears to be a fairly homogeneous population, there were significant differences in the types of women who access and who do not access cervical smear services. The underserved tend to be the older, poorer, less educated, and unemployed (or working in the informal sector) women. They tend to live in nonpermanent dwellings without a partner, they do not know anyone else who has had a cervical smear, and they have not recently sought care for other ailments, or used contraception. Cervical cancer is a slow-to-develop, eminently preventable disease, and yet opportunistic screening through antenatal and family planning services has failed to reach the women most at risk. Efforts in the future must include targeting older women in health centres where they present for other curative services (diabetes, hypertension). Most importantly, areas of the community with the greatest concentration of marginalized women need to be targeted through peer education and other innovative programs. As the underserved tend to be the poorer and less educated women in the community, we must ensure that messages are culturally relevant and appropriate and have a holistic focus on women's physical, mental, and emotional health.
Adult↗
Intravaginal practices, HIV and other sexually transmitted diseases among South African women.
BACKGROUND AND OBJECTIVES: Intravaginal practices, including wiping, douching, or inserting substances into the vagina, have been hypothesized to increase women's risk of HIV infection. However, data on the prevalence of these practices, and associations with HIV and other sexually transmitted diseases (STD), are limited. STUDY DESIGN: We interviewed 2,897 women participating in a gynecologic screening study in Cape Town, South Africa, about their intravaginal practices. After clinical examination, cervical and blood samples were collected and tested for HIV and other STD [corrected]. RESULTS: Of the 831 (29%) women reporting some type of intravaginal practice, 48% reported using only water and cloth to clean inside the vagina, whereas 17% reported using antiseptics or detergents. Most women (53%) reported practices as part of regular hygiene. Intravaginal practices were strongly associated with behavioral risk factors, and recent multiple sexual partners [corrected]. Intravaginal practices were associated with prevalent HIV infection (adjusted odds ratio, 1.74; 95% confidence interval, 1.37-2.20), but were not associated with other STDs. CONCLUSION: Prospective studies that include detailed measurements of correlated sexual risk behaviors are required to discern whether this association is causal in nature; if so, these behaviors could represent an important area for future HIV prevention interventions.
Adult↗
High prevalence of HPV 16 in South African women with cancer of the cervix and cervical intraepithelial neoplasia.
Despite the high prevalence of cervical cancer and cervical neoplasias in South Africa, few studies have been performed in this region to establish which human papillomavirus (HPV) types are associated with the development of high-grade cervical intraepithelial neoplasia lesions and cervical cancer. To investigate these prevalence rates, punch biopsies were obtained from 56 women with cervical cancer and 141 women with histologically diagnosed cervical intraepithelial neoplasia 2 or 3 lesions. Nested polymerase chain reaction (PCR) using consensus degenerate PCR primers was performed for the detection of HPV DNA and HPV typing was done by restriction fragment length polymorphism. Forty-seven (94%) of the cervical cancer and 114 (88%) of the cervical intraepithelial neoplasia 2/3 biopsies were positive for HPV DNA. The prevalence rates of the HPV types detected in the cervical cancer biopsies were HPV 16 (82%), HPV 18, (10%), HPV 33 (10%), HPV 31 (2%), HPV 58 (2%), HPV 35 (2%), and HPV 59 (2%). The cervical intraepithelial neoplasia lesions contained HPV 16 (56.6%), HPV 33 (14%), HPV 31 (10.9%), HPV X (7%), HPV 52 (3.9), HPV 58 (3.1%), HPV 35 (2.3%), HPV 18 (1.6%), HPV 11 (0.8%). Five of the nine fragments that were not typed by the RFLP, designated HPV-X, were sequenced to give HPV6 (1/5), HPV 26 (2/5), HPV 68 (1/5), and candHPV 87 (1/5). HPV 58 was detected in one cervical cancer biopsy and four biopsies from cervical intraepithelial neoplasia grade 3 lesions and was shown to be a previously described variant [Williamson and Rybicki (1991) J. Med. Virol. 33:165-171]. In addition, a cervical intraepithelial neoplasia grade 2 lesion was shown to harbour HPV type HAN2294 (cand HPV 87). The results of this study indicate that cervical cancer and cervical intraepithelial neoplasia 2/3 are largely associated with HPV 16 infection in this group of South African women and, therefore, an effective HPV 16 based vaccine should prevent the development of cervical cancer in a large proportion of women from this region of South Africa.
Adult↗