Lynne Gaffikin

A critical assessment of screening methods for cervical neoplasia

The objective of cervical cancer screening is to reduce cervical cancer incidence and mortality by detecting and treating precancerous lesions. Conventional cytology is the most widely used cervical cancer screening test. Although cytology has been effective in reducing the incidence of and mortality from cervical cancer in developed countries in both opportunistic and—more dramatically—organized national programs, it has been less successful and largely ineffective in reducing disease burden in low‐resource settings where it has been implemented. Liquid‐based cytology, testing for infection with oncogenic types of human papillomaviruses, visual inspection with 3–5% acetic acid, magnified visual inspection with acetic acid, and visual inspection with Lugols iodine have been evaluated as alternative tests. Their test characteristics, and the applications and limitations in screening, are discussed with an emphasis on the work of the Alliance for Cervical Cancer Prevention over the past 5 years.

Safety, acceptability, and feasibility of a single-visit approach to cervical-cancer prevention in rural Thailand: A demonstration project

BACKGROUND To increase screening and treatment coverage, innovative approaches to cervical-cancer prevention are being investigated in rural Thailand. We assessed the value of a single-visit approach combining visual inspection of the cervix with acetic acid wash (VIA) and cryotherapy. METHODS 12 trained nurses provided services in mobile (village health centre-based) and static (hospital-based) teams in four districts of Roi-et Province, Thailand. Over 7 months, 5999 women were tested by VIA. If they tested positive, after counselling about the benefits, potential risks, and probable side-effects they were offered cryotherapy. Data measuring safety, acceptability, feasibility, and effort to implement the programme were gathered. FINDINGS The VIA test-positive rate was 13.3% (798/5999), and 98.5% (609/618) of those eligible accepted immediate treatment. Overall, 756 women received cryotherapy, 629 (83.2%) of whom returned for their first follow-up visit. No major complications were recorded, and 33 (4.4%) of those treated returned for a perceived problem. Only 17 (2.2%) of the treated women needed clinical management other than reassurance about side-effects. Both VIA and cryotherapy were highly acceptable to the patients (over 95% expressed satisfaction with their experience). At their 1-year visit, the squamocolumnar junction was visible to the nurses, and the VIA test-negative rate was 94.3%. INTERPRETATION A single-visit approach with VIA and cryotherapy seems to be safe, acceptable, and feasible in rural Thailand, and is a potentially efficient method of cervical-cancer prevention in such settings.

Adjunctive testing for cervical cancer in low resource settings with visual inspection, HPV, and the Pap smear

Objective: To test whether the performance of visual inspection using acetic acid (VIA) could be improved through adjunctive testing and to determine whether the combination of visual inspection of the cervix and HPV testing could prove useful for identifying those at highest risk of cervical precancer. Methods: Between October 1995 and August 1997, 2199 women willing to be screened for cervical cancer in peri‐urban clinics in Harare, Zimbabwe received VIA, Pap smear and HPV as screening tests. The presence or absence of (pre)cancer was confirmed via colposcopy with biopsy as indicated for >97% of all women. Computerized simulations of sequential testing scenarios provided estimates of the joint (net) test qualities of different paired combinations of the three tests and allowed for comparisons with the individual test qualities. Results: Using HGSIL/CIN II‐III as the reference threshold of disease, the net sensitivity and specificity of VIA and HPV when used sequentially were 63.6 and 81.9%, respectively, compared to 43.3 and 91%, respectively, when Pap smears were followed by HPV testing. VIA followed by the Pap smear yielded a net sensitivity of 37.5% and net specificity of 94.3%. Conclusions: For programs with limited resources but with the capacity for HPV testing, sequential testing involving the use of VIA followed by HPV could yield fewer false positives than the use of VIA alone at a cost of relatively few additional false negatives.

HPV-based cervical cancer screening in a population at high risk for HIV infection.

We determined the utility of an assay for 13 cancer‐associated HPV types in primary cervical cancer screening of Zimbabwe women at high risk of HIV infection. HIV antibody status was determined by ELISA of oral mucosal specimens, and HPV DNA in the genital tract was identified by hybridization of cervical scrapes with probe B of Hybrid Capture II. Among the 466 women investigated, the prevalence of HPV, low‐grade squamous intraepithelial lesions (LGSIL) and high‐grade SIL (HGSIL) were 47.2%, 13.9% and 12%. Fifty‐three and one‐half percent of the women were HIV‐seropositive. As compared with HIV‐seronegative women, HIV‐infected women had a greater than 2‐fold HPV prevalence (64.3% vs. 27.6%), a greater than 7‐fold amount of HPV DNA (RLU of 82.6 vs. 10.7) in HPV+ women assessed as normal on the reference standard, and a nearly 3‐fold greater HGSIL prevalence (17.3% vs. 5.9%). The strong link between HGSIL and HPV DNA positivity was seen in both HIV‐infected and HIV‐seronegative women. The amount of HPV DNA increased with disease severity in both HIV‐seronegative and HIV‐infected women. The sensitivity and specificity of the HPV test for HGSIL were, respectively, 90.7% (95% confidence limit 77.9–97.4%) and 41.3% (34.5–48.3%) in HIV‐infected women and 61.5% (31.6–86.1%) and 74.5% (68.0–80.3%), respectively, in HIV− women. The usefulness of the HPV test as a screening test for cervical cancer in areas of high HPV prevalence will depend upon local health resource availability, disease priorities and policies regarding clinical case management. Int. J. Cancer 85:206–210, 2000. ©2000 Wiley‐Liss, Inc.

Performance of visual inspection with acetic acid for cervical cancer screening: a qualitative summary of evidence to date.

Developing countries often lack the necessary resources to use the Papanicolaou (Pap) smear as a screening tool for cervical abnormalities. Because the burden of cervical cancer is highest in such low-resource settings, alternative techniques have been sought. Recently, interest in visual inspection with acetic acid (VIA) has increased. Numerous studies have been conducted on its accuracy and its ability to detect cervical lesions when compared with other techniques, both conventional and nonconventional. This review summarizes key findings from the literature to provide researchers and policymakers with an up-to-date summary on VIA. PubMed was used to identify relevant journal articles published between 1982 and 2002. Key words were cervical cancer screening, visual inspection, VIA (visual inspection with acetic acid), DVI (direct visual inspection), AAT (acetic acid test), and cervicoscopy. Studies were eligible for review only if they involved analysis of primary VIA data (ie, not review articles); studies involving magnification devices were excluded. Fifteen studies were reviewed in total; key results were extracted and a summary analysis was performed for sensitivity and specificity parameters. When reported, sensitivity ranged between 66% and 96% and specificity between 64% and 98%. Authors comparing VIA with cytology noted that the overall usefulness of VIA compares favorably with that of the Pap test. The reported findings reviewed here suggest that VIA has the potential to be a cervical cancer screening tool, especially in low resource settings. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this article, the reader will be able to describe how visual inspection of the cervix for cervical cancer screening (VIA) is performed, to summarize the current literature on VIA, and to list potential advantages of VIA.

Uso de contracepção por adolescentes de escolas públicas na Bahia

OBJETIVO: O interesse sobre o comportamento contraceptivo de adolescentes vem crescendo, especialmente pela relevância social conferida a gravidez nessa faixa etaria. Assim, realizou-se estudo para investigar fatores associados ao uso de metodos anticoncepcionais entre adolescentes escolares. METODOS: Estudo transversal que utilizou um questionario auto-aplicado em 4.774 alunos de ambos os sexos, entre 11 e 19 anos. Calcularam-se as prevalencias de uso de contraceptivos na primeira e na ultima relacao sexual e em ambas as situacoes (uso consistente). A regressao logistica foi utilizada para a analise simultânea dos fatores e calculo de medidas ajustadas. RESULTADOS: Entre 1.664 estudantes com iniciacao sexual, os fatores associados positivamente ao uso consistente de contraceptivos pelos rapazes incluiram a iniciacao sexual mais tardia, com parceria estavel, contar com a familia como fonte potencial de contraceptivos e acesso a servicos de saude; entre as mocas, ter iniciado a vida sexual ha pouco tempo e ter o pai como fonte de informacao sobre sexualidade, contracepcao e prevencao DST/Aids. A gravidez foi relatada por 6,4% dos rapazes e 18,1% das mocas, sendo sua ausencia associada ao uso consistente de contraceptivos por elas (OR=3,83; 2,06-7,15). CONCLUSOES: Os resultados confirmam a complexidade da determinacao do comportamento contraceptivo entre adolescentes e a necessidade de que os programas educativos incorporem as multiplas dimensoes da questao para que tenham efetividade.

Evaluation of a human papillomavirus assay in cervical screening in Zimbabwe.

Objective To determine the utility of an assay for high risk genital human papillomavirus (HPV) in cervical screening in Zimbabwe, Africa.

Visual inspection with acetic acid as a cervical cancer test: accuracy validated using latent class analysis

BackgroundThe purpose of this study was to validate the accuracy of an alternative cervical cancer test – visual inspection with acetic acid (VIA) – by addressing possible imperfections in the gold standard through latent class analysis (LCA). The data were originally collected at peri-urban health clinics in Zimbabwe.MethodsConventional accuracy (sensitivity/specificity) estimates for VIA and two other screening tests using colposcopy/biopsy as the reference standard were compared to LCA estimates based on results from all four tests. For conventional analysis, negative colposcopy was accepted as a negative outcome when biopsy was not available as the reference standard. With LCA, local dependencies between tests were handled through adding direct effect parameters or additional latent classes to the model.ResultsTwo models yielded good fit to the data, a 2-class model with two adjustments and a 3-class model with one adjustment. The definition of latent disease associated with the latter was more stringent, backed by three of the four tests. Under that model, sensitivity for VIA (abnormal+) was 0.74 compared to 0.78 with conventional analyses. Specificity was 0.639 versus 0.568, respectively. By contrast, the LCA-derived sensitivity for colposcopy/biopsy was 0.63.ConclusionVIA sensitivity and specificity with the 3-class LCA model were within the range of published data and relatively consistent with conventional analyses, thus validating the original assessment of test accuracy. LCA probably yielded more likely estimates of the true accuracy than did conventional analysis with in-country colposcopy/biopsy as the reference standard. Colpscopy with biopsy can be problematic as a study reference standard and LCA offers the possibility of obtaining estimates adjusted for referent imperfections.

Screening test accuracy studies: how valid are our conclusions? Application to visual inspection methods for cervical screening

While the basic concepts associated with screening are simple, studying the value of new tests requires a very strict methodology. This paper summarizes lessons learned regarding appropriate methodologies to assess the value of new screening approaches using visual inspection with acetic acid (VIA), a screening test for cervical pre-cancerous lesions, as an example. In addition to being convenient to, safe for and acceptable by target community members, a screening test should be reliable and have good test characteristics (i.e. be able to discriminate well between early disease and non disease). Test reliability assesses the degree to which repeated measurements of the test yields the same result. To ensure reproducibility of study findings, test reliability should be assessed before any evaluation of test accuracy. The accuracy of a test (specificity and sensitivity) is measured using cross-sectional studies with adequate sample size. Several basic features are necessary to ensure internal validity for such studies: (a) final disease status data should be obtained for all subjects, (b) all tests results must be determined independently of previous results, (c) the reference standard used to determine the disease status should be accurate, (d) the full “spectrum” of the disease should be included in the study. The study results should also have external validity to be applicable to other populations to which the test will be applied. All these consideration are exemplified by 17 very heterogeneous studies published to date assessing VIA test accuracy. The assessment of a new screening test is the first step in researching a new cancer prevention strategy. For this reason, this step should be carefully addressed through rigorous studies.

Human papillomavirus genotype prevalence in high-grade squamous intraepithelial lesions and colposcopically normal women from Zimbabwe

Patti E. GRAVITT*, Anant M. KAMATH, Lynne GAFFIKIN, Z. Michael CHIRENJE, Sharita WOMACK and Keerti V. SHAH Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA JHPIEGO Corporation, Baltimore, MD, USA Department of Obstetrics and Gynecology, University of Zimbabwe, Harare, Zimbabwe