Human papillomavirus vaccination in low-resource countries: lack of evidence to support vaccinating sexually active women.

Vaccines against the human papillomaviruses (HPV) that cause around 70% of cervical cancer cases worldwide are highly efficacious when administered before infection with the viruses, which occurs soon after initiation of sexual activity. Despite recommendations from key public health bodies that the primary target population for HPV vaccination should be young adolescent girls, numerous articles have suggested widening the target age group to include older adolescent girls and adult women. These articles cite evidence of efficacy and cost-effectiveness when making recommendations, and they rarely take into account the difficult resource-allocation issues faced by decision makers in low-income countries. Authors and sponsors of these articles are usually from high-income countries and sometimes include vaccine manufacturers. This review discusses the strengths and weaknesses of several types of evidence offered by these papers in support of vaccination of a broad age range of girls and women. It concludes that the greatest public health benefit and value for resources will come from vaccinating girls before sexual debut and exposure to HPV, particularly in low-resource areas.

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.

An assessment of the readiness for introduction of the HPV vaccine in Uganda.

Formative research assessing human papillomavirus (HPV) vaccine readiness in Uganda was conducted in 2007. The objective was to generate evidence for government decision-making and operational planning for HPV vaccine introduction. Qualitative research methods with children, parents, teachers, community leaders, health workers, technical experts and political leaders were used to capture understanding of socio-cultural, health system and policy environments. We found low levels of knowledge about cervical cancer and HPV. Vaccination and its benefits were well-understood; respondents were positive about HPV vaccination. Health systems were deemed adequate for HPV vaccine delivery. Schools were identified as a vaccination venue, given high attendance by girls aged 10-12 years. Communication and advocacy strategies to foster acceptance should provide information on cervical cancer, HPV vaccine safety, and side effects. Policymakers requested further detail on costs. Introduction of HPV vaccine could be integrated into existing reproductive health and immunization policies.

Preventing cervical cancer in low-resource settings: how far have we come and what does the future hold?

The Alliance for Cervical Cancer Prevention (ACCP) came together in 1999 to answer key research questions and to advocate for greater global and national interest in reducing the heavy burden of morbidity and mortality caused by this preventable disease. Visual inspection with acetic acid (VIA), visual inspection with Lugol's iodine (VILI), and human papillomavirus (HPV) tests have been shown to be viable alternatives to traditional cytology. ACCP experience confirmed that cryotherapy is a safe and effective method that is acceptable to women and can be delivered by a range of health providers, including nonphysicians. Programs can maximize coverage by accommodating local needs and involving community leaders and women in planning and implementation. Advocacy efforts have led to significant policy changes and galvanized support for cervical cancer prevention. Despite the prospect of new HPV vaccines, screening will be needed for at least the next 30-40 years. Our experience has shown that with creativity, flexibility, and well-focused use of resources, the inequitable burden of cervical cancer borne by women in poor countries can be sharply reduced.

Visual inspection with acetic acid and cytology in the early detection of cervical neoplasia in Kolkata, India.

Visual inspection of the cervix after application of 3-5% acetic acid (VIA) is a potential alternative to cytology for screening in low-resource countries. The present study evaluated the performance of VIA, magnified visual inspection after application of acetic acid (VIAM), and cytology in the detection of high-grade cervical cancer precursor lesions in Kolkata (Calcutta) and suburbs in eastern India. Trained health workers with college education concurrently screened 5881 women aged 30-64 years with VIA, VIAM, and conventional cervical cytology. Detection of well-defined, opaque acetowhite lesions close to the squamocolumnar junction; well-defined, circumorificial acetowhite lesions; or dense acetowhitening of ulceroproliferative growth on the cervix constituted a positive VIA or VIAM. Cytology was considered positive if reported as mild dysplasia or worse lesions. All screened women (N = 5881) were evaluated by colposcopy, and biopsies were directed in those with colposcopic abnormalities (N = 1052, 17.9%). The final diagnosis was based on histology (if biopsies had been taken) or colposcopic findings, which allowed direct estimation of sensitivity, specificity, and predictive values. Moderate or severe dysplasia or carcinoma in situ (CIN 2-3 disease) was considered as true positive disease for the calculation of sensitivity, specificity, and predictive values of screening tests. 18.7%, 17.7% and 8.2% of the women tested positive for VIA, VIAM, and cytology. One hundred twenty two women had a final diagnosis of CIN 2-3 lesions. The sensitivities of VIA and VIAM to detect CIN 2-3 lesions were 55.7% and 60.7%, respectively; the specificities were 82.1% and 83.2%, respectively. The sensitivity and specificity of cytology were 29.5% and 92.3%, respectively. All the tests were associated with negative predictive values above 98%. VIA and VIAM had significantly higher sensitivity than cytology in our study; the specificity of cytology was higher than that of VIA and VIAM.

Screening and management of precancerous lesions to prevent cervical cancer in low-resource settings.

Cervical cancer is a leading cause of cancer death among women in low-resource settings, but it is completely preventable by screening for and treating precancerous lesions. In this article, the current approaches to screening, confirmation, and treatment of precancerous lesions of the cervix are reviewed from the perspective of low-resource settings. Cervical cytology is compared to visual inspection with acetic acid (VIA) for screening women to detect precancerous lesions. The use of colposcopy to confirm findings in women with positive screening test results and various treatment methods are discussed. With one examination, cytology appears to detect fewer precancerous lesions than VIA, but VIA has a lower specificity and labels proportionately more women falsely positive. When available, colposcopy may be used to obtain directed biopsies from abnormal areas of the cervix to pathologically confirm the findings in women with positive screening tests. Treatment with cryotherapy appears to be a safe, acceptable, and effective procedure for the majority of precancerous lesions. Lesions that are not suitable for cryotherapy because of endocervical canal involvement or large size are amenable to outpatient treatment by loop electrical excision procedure (LEEP). HIV/AIDS and immune system suppression are associated with more rapid CIN progression and HIV-positive women generally have high recurrence rates of CIN after treatment. Women tempora may more readily transmit the virus after cryotherapy and, therefore, they require counseling regarding abstinence and condom use. Highly active antiretroviral therapy (HAART) may cause CIN to regress and may decrease the risk of cervical cancer in HIV-infected women. Cost-effectiveness modeling using South African data shows that use of a single lifetime VIA test and immediate cryotherapy saves costs compared to cytology or to no screening. VIA and cryotherapy are appropriate services for low-resource settings. Colposcopy and LEEP services should be available on a referral basis.

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.

Effect of training with the american college of radiology breast imaging reporting and data system lexicon on mammographic interpretation skills in developing countries.

RATIONALE AND OBJECTIVES: The authors evaluated the effect of training in the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) lexicon on the interpretive skills of radiologists evaluating screening mammograms in Ukraine. MATERIALS AND METHODS: As part of a program to improve breast cancer detection and treatment in Ukraine, a series of training sessions was given to a group of radiologists across Ukraine to improve their interpretive skills in screening mammography. The training sessions focused on the use of the lexicon and assessment categories developed by the ACR BI-RADS committee. Participants (n = 14) evaluated 30 test screening mammograms before and after the training sessions. The test sets were randomly selected from a larger collection of training sets containing normal, benign, and abnormal mammograms. False-positive, false-negative, true-positive, and true-negative evaluations were determined, and sensitivity, specificity, and positive predictive values were calculated for each participant before and after training. RESULTS: The mean baseline sensitivity, specificity, and positive predictive values were 50%, 77%, and 43%, respectively. Each of these measures of interpretive skills improved significantly after training in the use of the lexicon, to 87%, 89%, and 78% (P < .0001, P < .01, and P < .0001, respectively). CONCLUSION: As the use of mammography spreads throughout developing countries, it is essential to address training and educational needs, as well as equipment needs. The ACR BI-RADS lexicon provides a systematic and efficient method for training radiologists to interpret screening mammograms. Educating radiologists on the use of this lexicon proved an effective way to improve their interpretive skills in screening mammography.

Cervical dysplasia treatment: key issues for developing countries.

Many developing countries face serious obstacles that have hindered establishment of successful cervical cancer control programs. Various countries are now seeking to strengthen cytology services and identify simple low-cost screening strategies; but any real gains in reducing cervical cancer incidence and mortality will also require effective treatment of women with preinvasive disease. Despite a trend toward conservative outpatient approaches for treating cervical dysplasia in industrialized countries, clinicians in many developing countries still rely primarily on invasive inpatient methods such as cone biopsy and hysterectomy. For women who could be treated with less invasive methods, these procedures tend to pose unnecessary risks and entail high costs that put them beyond the reach of many patients. Outpatient therapy, employing methods such as cryotherapy and the loop electrosurgical excision procedure (LEEP), combined with proper follow-up, is appropriate for dealing with visible lesions on the ectocervix when invasive cancer and endocervical involvement have been ruled out. Cryotherapy and LEEP hold out particular promise for developing countries because of their effectiveness, lack of side-effects, simplicity, and low cost. Cure rates range from 80% to 95%, depending on the method used and the severity of the lesions. However, each method has advantages and disadvantages that demand consideration. Various ways of reducing the number of follow-up visits, including the two-visit "see and treat" approach, are also available for use in areas where women's access to health services may be limited. A recent survey by the Program for Appropriate Technology in Health (PATH) affirmed the tendency to rely on cone biopsy and hysterectomy. It also found that in many places all degrees of preinvasive disease were treated, rather than only high-grade or severe conditions; that respondents in Latin America, the Caribbean, and Asia tended to use cryotherapy and LEEP more widely than other low-cost methods; that LEEP was preferred over cryotherapy in Latin America; and that colposcopes and other basic equipment needed to provide treatment were not consistently or widely available in some settings.

PIP: Financial, technical, and logistical factors have impeded the establishment of effective cervical cancer control programs in many developing countries. Efforts are now underway to strengthen cytology services and identify simple, inexpensive, alternative screening strategies that will improve early detection of cervical intraepithelial neoplasia (CIN). As part of this effort, the Program for Appropriate Technology in Health (PATH) surveyed the CIN treatment practices and preferences of 110 health practitioners from 33 developing countries. The survey revealed widespread reliance on invasive inpatient procedures such as cone biopsy and hysterectomy and a tendency to treat all preinvasive CIN, rather than only high-grade or severe CIN. Simple, low-cost, effective (80-95%) outpatient procedures such as cryotherapy and the loop electrosurgical excision procedure (LEEP) were selected more widely in Asia, the Caribbean, and Latin America than in Africa, but remained underutilized relative to inpatient treatments. In many settings, colposcopes and other basic equipment were not available. Respondents identified hysterectomy, cone biopsy, and LEEP as the most effective treatments of severe dysplasia. Overall, these findings suggest a need for more efficient use of scarce medical resources. Cryotherapy and LEEP, combined with proper follow-up, are particularly appropriate for developing countries in cases where invasive cancer and endocervical involvement have been ruled out.

Antenatal screening: its use in assessing obstetric risk factors in Zimbabwe.

STUDY OBJECTIVE: To assess the predictive utility of obstetric risk factors for identifying before the onset of labour those women at high risk of obstetric complications in a developing world setting, where home deliveries predominate and emergency transport is scarce. DESIGN: Risk factors derived from two population based, case-control studies (one of cephalopelvic disproportion and one of post partum haemorrhage), carried out in Zimbabwe were used to construct weighted and unweighted scores, a variety of screening algorithms, and sets of probabilities estimated from logistic regression models. These screening tests were evaluated for sensitivity, specificity, positive predictive value, and "cost" (the proportion of the population testing positive). Each complication was evaluated separately and the two were then pooled. PARTICIPANTS: All were Harare residents with singleton, vertex deliveries and spontaneous onset of labour. A total of 201 experienced cephalopelvic disproportion, 150 had post partum haemorrhage, and 299 had normal, unassisted deliveries. MEASUREMENTS AND MAIN RESULTS: Largely because of the very low incidence of the two complications studied (1% or less), positive predictive values were low (less than 7%). Holding "cost" constant at 10%, a screening test for cephalopelvic disproportion could predict 42.3% of cases compared with only 35.0% of those with post partum haemorrhage. Weighted scores had little advantage over unweighted ones, and probabilities from the logistic regression models did not differentiate cases from controls very well. CONCLUSIONS: With simple algorithms based on maternal height, parity, and obstetric history, more than one third of women at risk for potentially fatal complications could be identified at relatively small cost to themselves or the health care system.

Maternal height and age: risk factors for cephalopelvic disproportion in Zimbabwe.

Maternal age and stature are among several factors used to screen pregnant women for potential risk of labour complications. In a population-based case-control study in Harare, Zimbabwe, multivariate analysis was carried out to evaluate the importance of maternal age and height as risk factors for cephalopelvic disproportion (CPD). Using data abstracted from the medical records of 203 women with operative deliveries due to CPD and 299 women with normal unassisted vaginal deliveries, multiple logistic regression models were developed. Although maternal age < 18 years was not a significant risk factor in this study (perhaps because there were few women in this age group), advanced maternal age (> or = 35 years) was associated with a relative risk of 2.7 compared to women 20-34, after adjusting for other demographic and obstetric factors. Maternal height < 160 cm was associated with a twofold increased risk of CPD as compared to taller women.

PIP: In the Greater Harare area of Zimbabwe, a researcher compared data on 203 women who suffered from cephalopelvic disproportion (CPD) and underwent a cesarean section with data on 299 facility matched controls to determine the effects of maternal height and age and their significance for CPD. All the women delivered either at the municipal hospital or its clinics. When the researcher controlled for parity, young age (20 years) was not a risk factor. There were few 20-year old women, however. 35-year old mothers were at 2.1 times the risk for CPD than were 20.34 year olds after controlling for parity and at 2.7 times the risk after controlling for demographic and other obstetric factors. Women at a height of 160 cm had a relative risk for CPD of twice that of women at a height of 160 cm. Potential biases in this study included the possibility that women with prior cesarean section were underrepresented especially if they were selected for cesarean section for their short stature and questionable quality of the data in the medical records. This study was the 1st to document advanced maternal age as a risk factor for CPD but did not verify maternal youth as a risk factor. These results suggested that, even though short stature is a risk factor for CPD, there is a need to determine local cutoff points for screening purposes. Screening for CPD risk factors can reduce the likelihood of mothers having to endure prolonged labor.

Underutilization of health centers in rural Mexico: a qualitative approach to evaluation and planning.

PIP: A short field study of Durango, Mexico, is reported as a case study of a qualitative approach to evaluation. This approach uses a combination of methods, including in depth interviews, questionnaires, and participant/observation, to achieve a deeper understanding of program functioning and to provide a perspective unavailable from traditional quantitative measures. Recommendations for additional training for auxiliary nurses are offered.^ieng