Use of an expanded gold standard to estimate the accuracy of colposcopy and visual inspection with acetic acid.

We estimate the accuracy of colposcopy and visual inspection with acetic acid (VIA) while minimizing the effects of misclassification bias, and maximizing ascertainment of disease. VIA was performed by experienced physicians on a population-based sample of women aged 30 to 49 years in rural Shanxi province, China. Each woman received VIA, liquid-based cytology (LBC) and hybrid capture 2 (hc2, QIAGEN, Gaithersburg, MD; formerly Digene Corporation). Any woman who tested positive on any test had colposcopy, endocervical curettage (ECC) with directed biopsies as necessary and 4-quadrant random biopsies from normal-appearing areas of the cervix. A standard diagnosis based on colposcopy and directed biopsy, and an expanded diagnosis including ECC and 4-quadrant random biopsy were generated for each woman. In 1,839 women, use of the expanded versus the standard diagnostic criteria increased the prevalence of histologically confirmed high-grade cervical intraepithelial neoplasia and cancer (CIN2+) from 3.2% (59/1,839) to 4.2% (77/1,839) and decreased the sensitivity of VIA for CIN2+ from 69.5% (95% CI: 56.8-79.8) to 58.4% (95% CI: 47.3-68.8%) with little change in specificity of approximately 89%. Compared with the expanded diagnostic criterion, the sensitivity of a visual diagnosis of high-grade CIN or cancer by a colposcopist was 49.4% (95% CI: 38.2-60.5). The use of an expanded diagnostic criterion in this study yielded more conservative estimates of the sensitivity of VIA and colposcopy.

Colposcopists' agreement on cervical biopsy site.

OBJECTIVE: To determine the inter-observer agreement among colposcopists on the most abnormal area of the cervix from which a biopsy would be obtained and whether any attributes predict agreement. MATERIAL AND METHODS: Fifty cervigrams were reviewed and 72 colposcopists from five countries indicated the site to biopsy and whether an ECC should be obtained. Prior to the study, six Canadian colposcopists met to achieve consensus on the most diseased area for biopsy. Consensus was also reached on whether an ECC was indicated. For each cervigram, percent agreement was determined between each study colposcopist and the consensus. Data were analyzed to determine the attributes associated with the consensus response. RESULTS: The percent overall agreement of the colposcopists with the consensus diagnoses had a mean of 0.70 (95% CI, 0.65-0.75). The use of ECC was most common in Canada (15% of cases). The following factors were assessed by multivariate analysis to determine their influence on individual agreement with the consensus recommendation for the site to biopsy: country, duration of practice (less than or greater than 1 year), professional group (nurse, family doctor, pathologist, gynecologist, gynecologic oncologist), expert status (recognized national/international expert vs colposcopist), and gender. No factor was significantly associated. CONCLUSION: This international study was feasible and the level of inter-observer agreement among colposcopists on the location of the most severe lesions in cervical images is good.

Effectiveness and efficiency of selective vs universal screening for chlamydial infection in sexually active young women.

BACKGROUND: Since chlamydial cervicitis is not associated with specific complaints, screening asymptomatic women is an important initiative to prevent pelvic inflammatory disease and its sequelae. Compared with universal screening, selective screening is less costly but less effective so the cost savings vs the consequences of missing infected women need to be weighed carefully. METHODS: In two family planning clinics, 1002 women were surveyed for chlamydial infection (prevalence, 7%) and its predictors to determine whether universal or selective screening is the most efficient strategy. Two rules for the selection of patients were determined by logistic regression modeling and their relative efficiencies were compared by incremental cost-effectiveness and sensitivity analysis. The validity of the screening rules was tested in 191 students attending a university health clinic. RESULTS: If those with cervical friability, suspicious discharge, urinary frequency, or intermenstrual bleeding had been tested, 55.3% of all women would have been screened and 83.3% of all cases would have been detected. If those reporting a new sex partner in the preceding year had also been tested, 75.4% would have been screened, identifying 93.3% of all cases. The predictive power and practicality of the selection rules were validated in the university health clinic sample. Sensitivity analyses showed selective screening using cervical enzyme immunoassay with blocking confirmation was efficient if the prevalence of chlamydial infection was 16% or less, 11% or less, or 5% or less depending on whether base analyses, overestimated costs, or worst performance scenarios, respectively, were used. CONCLUSIONS: Selective screening based on four or five predictors and confirmed cervical enzyme immunoassay is an effective and efficient strategy in low prevalence settings.

Training for cervical cancer prevention programs in low-resource settings: focus on visual inspection with acetic acid and cryotherapy.

The modern approach to cervical cancer prevention, characterized by use of cytology and multiple visits for diagnosis and treatment, has frequently proven challenging and unworkable in low-resource settings. Because of this, the Alliance for Cervical Cancer Prevention (ACCP) has made it a priority to investigate and assess alternative approaches, particularly the use of visual screening methods, such as visual inspection with acetic acid (VIA) and visual inspection with Lugol's iodine (VILI), for precancer and cancer detection and the use of cryotherapy as a precancer treatment method. As a result of ACCP experience in providing training to nurses and doctors in these techniques, it is now widely agreed that training should be competency based, combining both didactic and hands-on approaches, and should be done in a clinical setting that resembles the service-delivery conditions at the program site. This article reviews ACCP experiences and perceptions about the essentials of training in visual inspection and cryotherapy and presents some lessons learned with regard to training in these techniques in low-resource settings.

Observer variability in the scoring of colpophotographs.

Colposcopy and cervicography are accepted tools for assessing the cervix for an atypical transformation zone. We studied the validity of the colpophotograph as a measurement tool by determining the agreement of experienced colposcopists using colpophotographs of 50 women. Interobserver agreement was generally fair to good (kappa greater than or equal to 0.40) for the presence of the squamocolumnar junction and the area of ectopia but it was poor (kappa less than 0.40) for the area, border, and color characteristics of an atypical transformation zone. Intra-observer agreement was fair to good for the color characteristics of an atypical transformation zone, but it was poor for the area and border characteristics. We conclude that observer agreement studies should play a role in the validation of methods used in the visual diagnosis of cervical intraepithelial neoplasia. Considerable lack of agreement in reporting cytologic findings is a well-known problem, and lack of agreement might be an even bigger problem in reporting colposcopic findings.

Assessment of the cervix after acetic acid wash: inter-rater agreement using photographs.

OBJECTIVE: To estimate the inter-rater agreement on the assessment of cervical photographs after acetic acid wash, using visual inspection with acetic acid categories. METHODS: Three raters individually assessed 144 photographs as negative, positive, or suspicious for cancer. The inter-rater agreement was analyzed using the unweighted and weighted kappa coefficient. To explore the reasons for concordancy and discordancy, photographs were compared on histologic evidence of cervical intraepithelial neoplasia and on testing for oncogenic types of human papillomavirus. RESULTS: Overall raw agreement among the three raters was 66.7% (96 of 144) with a kappa of 0.57 (95% confidence interval 0.48, 0.66). Pair-wise agreement using unweighted and weighted kappa was moderate to substantial: 0.54-0.60 and 0.56-0.63, respectively. There was concordance on negative in 25.7% (37 of 144) and on positive or suspicious for cancer in 41.0% (59 of 144). Cervical intraepithelial neoplasia II or III was not present on biopsy if photographs were concordant-negative, and the human papillomavirus test was less likely to be positive (relative risk 0.3; 95% confidence interval 0.2, 0.6) in concordant-negatives compared with concordant-positives, including suspicious for cancer. Cervical intraepithelial neoplasia II or III was more common in photographs that were concordant-positive, including suspicious for cancer, compared with discordants (relative risk 3.4, 95% confidence interval 1.5, 7.6). CONCLUSION: Based on photographs of the cervix taken after acetic acid wash, the level of agreement among raters using visual inspection with acetic acid categories was moderate to substantial, consistent with other commonly used tests.

Tubal factor infertility: an association with prior chlamydial infection and asymptomatic salpingitis.

In 265 Canadian women, with and without tubal factor infertility (TFI), we compared Chlamydia trachomatis cultures of endocervical swabs, endotubal swabs and biopsies, serology, and past history. A history of pelvic inflammatory disease (PID) was absent in 69.2% of TFI women, despite visual evidence of tubal damage. C. trachomatis was not isolated in any of 52 patients with TFI (TFI group), 114 having tubal ligation (STER group), or 99 patients having hysterectomy (HYST group). However, chlamydial antigen was detected with an immunochemical method in 1 of 16 tubal biopsy specimens from TFI women. The prevalence of chlamydial IgM or IgG antibody in serum was significantly higher (P less than 0.0001) in the TFI group (79.1%) than in the other two groups (relative odds, 6.3; 95% confidence interval: 2.5, 16.8). In seropositive (IgG or IgM) subjects, there was a significant (P = 0.003) and strong (relative odds, 5.1; 95% confidence interval: 1.5, 18.1) association between chlamydial IgA antibody and TFI. In women with TFI, there was no significant association between IgM or IgG seropositivity (P = 0.56). or IgA seropositivity (P = 0.53), and a negative history for PID. These findings are consistent with the hypothesis that C. trachomatis is a major cause of TFI following PID, which may or may not be asymptomatic.

Imiquimod 5% cream is a safe and effective self-applied treatment for anogenital warts--results of an open-label, multicentre Phase IIIB trial.

Our objective was to determine the efficacy and safety of imiquimod 5% cream in the treatment of external genital/perianal warts in an open-label Phase IIIB trial. Patients applied imiquimod 5% cream 3 times per week, for up to 16 weeks. Those who cleared their warts were monitored during a 6-month follow-up period. If their warts recurred, or new warts developed during this time, patients could be re-treated for up to 16 additional weeks. Patients who experienced partial clearance during the initial treatment period entered an extended treatment period of up to an additional 16 weeks. A total of 943 patients from 114 clinic sites in 20 countries participated in this study. Complete clinical clearance was observed in 451/943 (47.8%) patients (intent-to-treat (ITT) analysis) during the initial treatment period, with clearance in an additional 52 (5.5%) patients during the extended treatment period beyond 16 weeks. The overall clearance rate for the combined treatment periods was 53.3%. In a treatment failure analysis, the overall clearance rate was 65.5%; a greater proportion of female patients (75.5%) experienced complete clearance than male patients (56.9%). Low recurrence rates, of 8.8% and 23.0%, were observed at the end of the 3- and 6-month follow-up periods, respectively. The sustained clearance rates (patients who cleared during treatment and remained clear at the end of the follow-up period) after 3 and 6 months were 41.6% and 33.0% (ITT analysis), respectively. Local erythema occurred in 67% of patients. In the majority of patients local skin reactions were of mild to moderate severity. In conclusion, imiquimod 5% cream is an effective self-applied treatment for external genital/perianal warts when applied for up to 16 weeks and is well tolerated for up to 32 weeks.

Screening seniors for risk of functional decline: results of a survey in family practice.

OBJECTIVE: To measure functional status, determine risk of functional decline and assess consistency between responses and standardized instruments. DESIGN: A mailed survey which measured functional impairment, recent hospitalization and bereavement. A positive response on at least one of these factors indicated that the individual was "at risk" for functional decline. A random sample (n = 73) of "at risk" subjects (specifically, family practice patients aged 70 and older) were assessed by a nurse. RESULTS: The response rate was 89% (369/415), 59% of seniors were female and the mean age was 77.1 (SD = 5.5) years. Self-reported risk, based on activities of daily living (ADLs), was associated with impairment in at least one basic ADL (p < 0.0005) using a standardized instrument. The positive predictive value of the survey for ADL impairment was 65%. CONCLUSION: Response to a mailed survey was high and self-reported ADL risks were consistent with findings from standardized assessment tools.

Partner notification for sexually transmitted diseases: an overview of the evidence.

OBJECTIVE: To compare the effectiveness of alternative partner notification strategies for gonorrhea, chlamydia, syphilis, HIV and hepatitis B. DATA SOURCES: Studies were identified using MEDLINE, EMBASE, SCISEARCH and other databases, review of reference lists and personal contact with over 80 international experts. STUDY SELECTION: Studies with at least two comparison groups exposed to different partner notification strategies were included. DATA EXTRACTION: Methodological rigor was assessed, and information regarding study populations, interventions and outcomes was extracted independently by two reviewers. MAIN RESULTS: Twelve studies met our inclusion criteria; five were methodologically strong; seven provided data on the referral process; four provided data on trained interviewers compared with routine care providers; and three provided data on the interview process. CONCLUSIONS: Only limited, broad conclusions regarding the effectiveness of various partner notification approaches could be drawn from these comparative studies. Until newer data become available, practice guidelines must be based to a large extent on other grounds.

Partner notification for sexually transmitted diseases: proposed practice guidelines.

Using the results of an analysis of available scientific evidence and a survey of current practice in Canada, as well as expert opinion, these guidelines attempt to consider current partner notification practice in Canada and recommend an approach to determining practice which is flexible enough to address local circumstances. Priority areas for future research were also identified.

A survey of public health partner notification for sexually transmitted diseases in Canada.

OBJECTIVE: To describe the range of practice for sexually transmitted disease (STD) contact tracing/partner notification (PN) by public health agencies in Canada. METHODS: A two-level mailed survey, using two different questionnaires, was conducted from Aug. 1991 to Feb. 1992, directed to: 1) provincial and territorial epidemiologists/directors of STD control, asking about program organization; and 2) 154 local health units/provincially run PN programs, asking about practice patterns of STD partner notification. CONCLUSIONS: In Canada, STD PN by public health agencies is routinely practised in most provinces. PN efforts vary by the STD; less PN effort goes to chlamydia despite a high burden of illness; HIV PN is frequently perceived to be within the responsibility of the physician. For STDs with higher PN effort, the preferred method is provider referral. Targeting is seldom utilized, and there are little available data at a local level monitoring even process measures of effectiveness.

Confirmation of cervical neoplasia using a hand-held, lighted magnification device.

OBJECTIVES: The objective of this study was to estimate the sensitivity and specificity of visual inspection with acetic acid and magnification (VIAM) using the AviScope device to confirm high-grade cervical intraepithelial neoplasia or carcinoma. METHODS: VIAM was performed on 142 women aged 18-50 years referred to three colposcopy clinics because of abnormal cervical cytology. Each woman then had a colposcopic examination with cervical biopsy when indicated. RESULTS: The AviScope device identified 24 of the 40 women who had CIN 2, 3, or carcinoma, yielding a sensitivity of 60.0% (95% CI 43.4, 74.7). The AviScope correctly identified 60 of 87 women negative for dysplasia or cancer, yielding a specificity of 69.0% (95% CI 58.0, 78.2) compared with colposcopy and cervical histology. CONCLUSION: VIAM using the AviScope device was moderately sensitive and specific for the confirmation of high-grade cervical lesions in women referred with abnormal cervical cytology.

A comparison of triage methods for Kenyan women who screen positive for cervical intraepithelial neoplasia by visual inspection of the cervix with acetic acid.

BACKGROUND: Only about one in seven visual inspection with acetic acid (VIA)-positive women has high-grade disease; further confirmatory testing could rule out false positives. OBJECTIVES: To determine if visual inspection with Lugol's iodine (VILI) or visual inspection with acetic acid and magnification (VIAM) can accurately confirm the presence of disease among rural Kenyan women referred to a district hospital because of a VIA-positive result at a primary health facility. METHODS: Referred women received cervical cytology and either VILI and/or VIAM as triage methods. All women were assessed by colposcopy and biopsied, if necessary. RESULTS: Of the 490 VIA-positive subjects referred, 332 (68%) attended the district hospital and received at least one of two triage tests and cervical cytology. The sensitivity and specificity for histologically-confirmed CIN 2 and 3 were 93% (14/15) and 32% (52/161) for VIAM; 100% (3/3) and 77% (49/64) for VILI; and 80% (16/20) and 48% (110/228) for cervical cytology. VILI reduced the number of false-positive screening results by 73%, without missing any true positives. CONCLUSIONS: VILI had comparable sensitivity and significantly higher specificity compared to VIAM and cervical cytology. VILI may be a promising triage test for screen-positive women in low-resource settings; additional research is required.

Report on a cryotherapy service for women with cervical intraepithelial neoplasia in a district hospital in western Kenya.

BACKGROUND: In low-resource settings, cryotherapy can be cost-effective, affordable, and a first-line treatment for cervical intraepithelial neplasia (CIN) of any grade. OBJECTIVES: To report the acceptability, safety and effectiveness of cryotherapy for women with cervical intraepithelial neoplasia (CIN) in Western Kenya. METHODS: Visual inspection with acetic acid (VIA)-positive women and those suspected of having cervical cancer based on an initial evaluation at a primary health facility were referred to the district hospital for colposcopy and additional evaluation using visual inspection with Lugol's iodine (VILI) and/or visual inspection with acetic acid and magnification (VIAM). Cryotherapy was offered immediately to women diagnosed with appropriate CIN lesions based on colposcopy or after waiting for a confirmatory cervical biopsy and a follow up visit occurred one year later. RESULTS: Ninety one 91 women 30 to 39 years of age had CIN appropriate for cryotherapy. Approximately 36% (24/67) were due for their 1 year follow up visit and 20 of 24 (83.3%) attended. Complete data were available for 18 of 20 (90%) and 13 (72.2%) had no sign of CIN. No serious adverse events were reported 1 to 3 months after cryotherapy. All respondents reported that the treatment experience was acceptable. CONCLUSIONS: Cryotherapy was acceptable, safe and effective.

Vaginal self sampling versus physician cervical sampling for HPV among younger and older women.

OBJECTIVES: To estimate the agreement between self collected vaginal swabs and physician collected cervical brush samples for detection of oncogenic human papillomavirus infection (HPV) by the hybrid capture 2 (HC-2) test among women younger and older than 50 years, and to assess women's preference for sample collection method based on age. METHODS: Consecutive women aged 15-49 years due for a 1 year visit in a prevalence study of carcinogenic HPV and a new sample of women aged 50 years and older attending their family physicians for cervical screening, in Ontario, Canada, performed vaginal self sampling and underwent physician cervical sampling and cervical cytology. Women completed a self administered questionnaire on demographics and preference for sampling method. RESULTS: Among the 307 women aged 15-49 years, the prevalence of HPV was 20.8% (64/307) and 17.6% (54/307) in the vaginal and cervical specimens, respectively. Among the women aged 50 years and older, prevalence was 9.9% (15/152) and 8.6% (13/152), respectively. Kappa for agreement between sample collection methods was 0.54 for the younger and 0.37 for the older women (both p< 0.001). Nearly half of the women preferred self sampling or had no preference. CONCLUSIONS: There was fair agreement between self collected vaginal and physician collected cervical specimens for detecting carcinogenic HPV in younger and older women. Vaginal sampling for HPV appears to be promising as a primary screening strategy for cervical cancer prevention programmes in low resource settings in developed and developing countries.

Diagnostic accuracy of self collected vaginal specimens for human papillomavirus compared to clinician collected human papillomavirus specimens: a meta-analysis.

BACKGROUND/OBJECTIVES: Providing summary recommendations regarding self collection of vaginal specimens for human papillomavirus (HPV) testing is difficult owing to the wide range of published estimates for the diagnostic accuracy of this approach. To determine summary estimates from analyses of reported findings of the sensitivity, specificity and summary receiver operating characteristic curves (SROC) for self collected vaginal specimens for HPV testing compared to the reference standard, clinician collected HPV specimens. METHODS: Standard search criteria for a diagnostic systematic review were employed. Eligible studies were combined using a random effects model and summary ROC curves were derived for overall and for specific subgroups. RESULTS: Summary measures were determined from 12 studies. Six studies where patients used Dacron or cotton swabs or cytobrushes to obtain samples were pooled and had an overall sensitivity of 0.74 (95% CI 0.61 to 0.84) and specificity of 0.88 (95% CI 0.83 to 0.92), with diagnostic odds ratio of 22.3 and an area under the curve of 0.91. Self specimens using Dacron or cotton swabs or cytobrushes collected by women enrolled at referral clinics had an overall sensitivity of 0.81 (95% CI 0.65 to 0.91) and specificity of 0.90 (95% CI 0.80 to 0.95). Sensitivity and specificity of tampons ranged from 0.67-0.94 and 0.80-0.85 respectively. CONCLUSIONS: Our findings indicate that the combined sensitivity for HPV-DNA is more than 70% when patients use Dacron swabs, cotton swabs, or cytobrushes to obtain their own vaginal specimens for HPV-DNA evaluation. Self collected HPV-DNA swabs may be an appropriate alternative for low resource settings or in patients reluctant to undergo pelvic examinations.

The copper-7 intrauterine contraceptive device: 5-year evaluation.

Over a 5-year period a family practitioner inserted copper-7 (Cu-7 intrauterine contraceptive devices (IUDs) in 134 women. The rates of continued use after 2 years, 53.0% for the women's first IUD and 63.9% for all their IUDs, and of accidental pregnancy, 2.4%, are comparable to those in the literature. However, in this series the rate of expulsion was 0.8%, much lower than that in the literature. Fertility did not appear to be reduced in women who planned to have pregnancies after the device was removed. A carefully scrutinized technique of insertion and conscientious follow-up make the Cu-7 IUD an acceptable form of contraception for many patients in a family practice.

Lipid screening in family practice: a critical appraisal of recent evidence.

Applying principles of critical appraisal to evidence for lipid screening in family practice, one concludes that elevations of triglyceride are not a defined risk for coronary heart disease at present and screening cannot be justified. In contrast, there is now good evidence that elevated cholesterol is not only a primary risk factor for, but also a cause of coronary heart disease. There has been no randomized trial of cholesterol screening to date, leaving the physician in the position of knowing something should be done about the problem, but the best methods are yet to be clarified.

Pelvic inflammatory disease: a family practice perspective.

Most women with symptomatic acute pelvic inflammatory disease (PID) are now managed outside of hospital by private practitioners. Clinical diagnosis of PID is often inaccurate, but can be improved by knowledge of risk factors, use of simple investigations, and referral for laparoscopy when the physician is unsure. Prompt treatment with a recommended regimen that includes at least two antibiotics, careful consideration of when to hospitalize or refer, and an awareness of the need for compliance and follow up are important attributes of good management. In contrast, asymptomatic PID, which is a common antecedent of tubal factor infertility and ectopic pregnancy, can be prevented only by screening for and appropriate treatment of sexually transmitted infections.