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. ‍     

Evaluation of Provider Skills in Performing Visual Inspection with Acetic Acid in the Cervical Cancer Screening Program in the Meknes-Tafilalet Region of Morocco

Background: This study documented the performance of providers of visual inspection with acetic acid (VIA) at primary health centers, assessing their compliance with the VIA skills checklist and determinants of non-compliance, and exploring their perceptions of VIA training sessions. Materials and Methods: A cross- sectional study was conducted among VIA providers in the Meknes-Tafilalet region of Morocco. Structured observation of their performance was conducted through supervisory visits and multiple focus group discussions (FGDs). Results: Performance of all the recommended steps for effective communication was observed in a low proportion of procedures (36.4%). Midwives/nurses had higher compliance than general practitioners (GPs) (p<0.001). All recommended steps for VIA examination were performed for a high proportion of procedures (82.5%). Compliance was higher among midwives/nurses than among GPs (p<0.001) and among providers in rural areas than those in urban areas (p<0.001). For pre-VIA counselling, all recommended steps were performed for only 36.8% of procedures. For post-VIA counseling, all recommended steps were performed in a high proportion (85.5% for VIA-negative and 85.1% for VIA-positive women). Midwives/nurses had higher compliance than GPs when advising VIA-positive women (p0.009). All infection prevention practices were followed for only 14.2% of procedures, and compliance was higher among providers in rural areas than those in urban areas (p<0.001). Most FGD participants were satisfied with the content of VIA training sessions. However, they suggested periodic refresher training and supportive supervision. Conclusions: Quality assurance of a cervical cancer screening program is a key element to ensure that the providers perform VIA correctly and confidently.     

A cluster randomized controlled trial of visual, cytology and human papillomavirus screening for cancer of the cervix in rural India

The impact of screening by visual inspection with acetic acid (VIA), cytology or HPV testing on cervical cancer incidence and mortality is investigated in a cluster randomized controlled trial in India. We report findings after the screening phase, when 52 clusters, with a total of 142,701 women aged 30-59 years in Osmanabad District, India, were randomized into 4 arms for a single round of screening by trained midwives with either VIA, cytology or HPV testing as well as a control group. All laboratory tests were done locally. Test-positive women underwent investigations (colposcopy/biopsy) and treatment in the base hospital. Data on participation, test positivity, positive predictive value and detection rates of cervical neoplasia were analyzed using cluster design methodology. Of the eligible women, 72-74% were screened. Test positivity rates were 14.0% for VIA, 7.0% for cytology and 10.3% for HPV. The detection rate of high-grade lesions was similar in all intervention arms (0.7% for VIA, 1.0% for cytology and 0.9% for HPV testing) (p = 0.06, Mann-Whitney test). While the detection rate for VIA dropped to 0.5% with declining test positivity during the course of the study, it remained constant for cytology and HPV testing. Over 85% of women with high-grade lesions received treatment. Our results show that a high level of participation and good-quality cytology can be achieved in low-resource settings. VIA is a useful alternative but requires careful monitoring. Detection rates obtained by HPV testing were similar to cytology, despite higher investments.     

重庆市宫颈癌机会性筛查方法研究

[目的]分析重庆市宫颈癌机会性筛查的基本现状,探索适合重庆市宫颈癌机会性筛查方法。[方法]收集分析2009年重庆市8家医院机会性筛查资料,筛查方法包括液基细胞学、巴氏涂片、HPVDNA检测,以及专家推荐的三种筛查方案,Ⅰ方案：HPV检测和液基细胞学组合;Ⅱ方案：传统巴氏涂片和HPV检测;Ⅲ方案：仅用肉眼观察（醋酸或碘染色法,VIA/VILI）。病理确诊宫颈病变及宫颈癌,并对受检妇女进行流行病学调查。[结果]筛查过程中医生实际使用液基细胞学2390例（64.26%）,Ⅲ方案2300例（61.84%）,巴氏涂片194例（5.22%）,Ⅰ方案103例（2.77%）,Ⅱ方案52例（1.40%）,HPVDNA检测17例（0.46%）,最普遍采用的方法是液基细胞学、肉眼观察。检出CIN217例,检出率为9.68%;宫颈癌22例,检出率为0.98%。对受检妇女进行流行病学调查显示,愿意选择液基细胞学所占比例（69.69%）最高,其次分别为阴道镜（47.26%）、VIA/VILI（40.04%）、巴氏涂片（4.35%）,所占比例最低为HPVDNA（3.54%）,而经济欠发达、文化程度低、年长者、家人未患有肿瘤者更愿意选择传统筛查方法。[结论]不管是筛查过程中医生实际使用,还是受检妇女的选择,均是以细胞学为重庆市宫颈癌的主要检测手段,液基细胞学正逐步被广泛使用;而肉眼观察仍为重庆市经济欠发达地区宫颈癌筛查的另一主要检测手段。     

Accuracy of concurrent visual and cytology screening in detecting cervical cancer precursors in rural India

The high burden of cervical cancer and inadequate/suboptimal cytology screening in developing countries led to the evaluation of visual screening tests, like visual inspection with acetic acid (VIA) and Lugol's iodine (VILI). We describe the performance of VIA, VILI and cytology, carried out in a multinational project called "Screening Technologies to Advance Rapid Testing" in 5,519 women aged 30-49 years, in detecting cervical intraepithelial neoplasia (CIN). VIA, VILI and cytology were positive in 16.9%, 15.6% and 6.1% women, respectively. We found 57 cases of CIN2, 55 of CIN3 and 12 of cervical cancer; 90% of CIN3 and 43% CIN2 cases were positive for p16 overexpression and high-risk HPV infection, indicating a high validity of histological diagnosis. The sensitivity of VIA, VILI and cytology to detect high-grade CIN were 64.5%, 64.5% and 67.7%, respectively; specificities were 84.2%, 85.5% and 95.4%. A high proportion of p16 positive CIN 3 (93.8%) and 2 (76.9%) were positive on cytology compared with visual tests (68.8% and 53.8%, respectively) indicating a higher sensitivity of cytology to detect p16 positive high-grade CIN. However, the immediate availability of the results from the visual tests permits diagnosis and/or treatment to be performed in the same sitting, which can potentially reduce loss to follow-up when women must be recalled following positive cytology. Organizing visual screening services in low-resource countries may facilitate the gradual building of an infrastructure committed to screening allowing the eventual introduction of more sensitive, highly objective, reproducible and affordable human papillomavirus screening tests in future.     

Cervical screening by visual inspection, HPV testing, liquid-based and conventional cytology in Amazonian Peru

Cervical cancer is an important public health problem in many developing countries, where cytology screening has been ineffective. We compared four tests to identify the most appropriate for screening in countries with limited resources. Nineteen midwives screened 5,435 women with visual inspection (VIA) and collected cervical samples for HPV testing, liquid-based cytology (LBC) and conventional cytology (CC). If VIA was positive, a doctor performed magnified VIA. CC was read locally, LBC was read in Lima and HPV testing was done in London. Women with a positive screening test were offered colposcopy or cryotherapy (with biopsy). Inadequacy rates were 5% and 11% for LBC and CC respectively, and less than 0.1% for VIA and HPV. One thousand eight hundred eighty-one women (84% of 2,236) accepted colposcopy/cryotherapy: 79 had carcinoma in situ or cancer (CIS+), 27 had severe- and 42 moderate-dysplasia on histology. We estimated a further 6.5 cases of CIS+ in women without a biopsy. Sensitivity for CIS+ (specificity for less than moderate dysplasia) was 41.2% (76.7%) for VIA, 95.8% (89.3%) for HPV, 80.3% (83.7%) for LBC, and 42.5% (98.7%) for CC. Sensitivities for moderate dysplasia or worse were better for VIA (54.9%) and less favourable for HPV and cytology. In this setting, VIA and CC missed the majority of high-grade disease. Overall, HPV testing performed best. VIA gives immediate results, but will require investment in regular training and supervision. Further work is needed to determine whether screened-positive women should all be treated or triaged with a more specific test.     

两次醋酸染色肉眼观察在宫颈癌筛查中的价值

[目的]探讨两次醋酸染色肉眼观察(VIA)在宫颈癌筛查中的应用价值。[方法]2011年对2463名河南省新密市25～65岁的妇女进行HPV检测、VIA的联合筛查,任一筛查阳性者和10%随机抽取的筛查阴性者共855名妇女进行第二次VIA和阴道镜检查。[结果]最终完成两次VIA、阴道镜检查及宫颈活检的855名妇女,其中未绝经组561人,绝经组294人。未绝经组和绝经组第一次VIA的阳性率分别为19.8%(111/561)和7.1%(21/294),灵敏度分别为59.1%和20.0%,特异性分别为81.8%和93.6%。未绝经组和绝经组进行第二次VIA的阳性率分别为15.7%(88/561)和5.8%(17/294)。未绝经组和绝经组进行两次VIA检查总的阳性率分别为27.3%和10.2%,两次VIA检查并联的灵敏度分别为81.8%和40.0%,特异性分别为75.0%和91.4%。未绝经组通过两次VIA检查比单独一次VIA检查多发现5例CIN2+的漏诊病例(1例CIN2,4例CIN3),绝经组通过两次VIA检查比单独一次VIA检查多发现3例CIN3的漏诊病例。[结论]宫颈癌筛查中,两次VIA检查不仅可以明显提高单次VIA检查的灵敏度,还可以发现单次VIA检查漏诊的高度CIN病例。两次VIA在未绝经女性宫颈癌筛查中的价值优于绝经组。     

A Comparison of Cytology with Pap Smears Taken by a Gynecologist and with a Self-sampling Device

Cervical cancer is the most common cancer in Thai women and as yet screening programmes are minimally ‍effective. The Pap smear is the test accepted to be most appropriate for cervical cancer screening so far. One of the ‍main reasons why women do not come to have Pap smear done is “shyness”, which weakens compliance with ‍recommendations to undergo Pap smear with pelvic examination. The self-administered device by the Kato method ‍was established to overcome this problem and the present study was carried out to confirm the adequacy of the ‍specimens obtained with this technique in comparison with specimens collected by gynecologists. Two hundred ‍women were invited to participate in the study voluntarily. Each was allocated to have a Pap smear conducted by a ‍gynecologist and then instructed to produce a self-obtained smear using Kato’s device. The cytology results of Pap ‍smears from both methods were compared to test for agreement using Kappa statistics. ‍There was agreement between the adequacy of smears collected by gynecologists and those self-sampled with the ‍percentage agreement of 96.5% and a Kappa score of 0.43 (95% CI 0.33-0.54, P<0.001). There were 8 cases detected ‍as epithelial cell abnormalities from the cervical cells collected by gynecologists and also with the self-administered ‍technique. Good agreement for detection of cellular changes was found with a percentage of 78.0% and the Kappa’s ‍score was 0.61 (95% CI 0.46-0.76, P<0.001). The results from this study provide convincing evidence that the selfadministered ‍device can be an alternative choice for women who are too shy to undergo pelvic examination or even ‍for those who have limited time to visit health care centers or doctors to have a Pap smear test.     

Prevalence of Cervical Dysplasia in HIV-Positive and HIV-Negative Women at the Sihanouk Hospital Center of HOPE,Phnom Penh,Cambodia

Introduction: There is a high burden of cervical cancer in Cambodia, yet published data on the prevalence of cervicaldysplasia and the risk factors contributing to the development of pre-cancerous lesions in Cambodian women is verylimited. In addition, as it is well known that HIV positivity increases cervical cancer risk, it is important to quantifythe prevalence of cervical dysplasia and carcinoma among Cambodian women living with HIV disease. Methods: Across-sectional study was conducted with a sample of 499 HIV+ and 501 HIV- Cambodian women at the SihanoukHospital Center of HOPE. Visual inspection with 5% acetic acid was the method of screening. Colposcopy was performedon all VIA+ patients, and subsequent treatment followed WHO guidelines. Logistic regression models, stratified byboth HIV+ and HIV- groups, were used to assess significant factors associated with having dysplasia. Results: VIA+results were prevalent in both the HIV+ and HIV- arms of the study. The HIV+ patients were more likely to have alower age at coitarche, lower weight, 2 or more lifetime sexual partners, two or greater pregnancies, or be unmarried.The estimated prevalence of VIA detected cervical dysplasia was 11% for the entire study sample, 13.4% in the HIVpositive (HIV+) group and 8.6% in the HIV negative (HIV-) group (OR: 1.65; 95% CI: 1.10, 2.48; p=0.01). For theHIV+ group, having a history of 4 or more full-term pregnancies (OR: 3.42; 95% CI: 1.01-11.64; p=0.049) was foundto be significantly associated with having an increased risk of developing cervical dysplasia in the multivariate model.Conclusion: Cervical dysplasia is prevalent in both HIV positive and negative Cambodian women and a VIA basednational screening programs need to be developed and expanded to provide access to affordable and effective treatmentfor cervical dysplasia and cancers.     

Risk assessment to guide cervical screening strategies in a large Chinese population

Three different cervical screening methods [cytology, human papillomavirus(HPV) testing and visual inspection with acetic acid(VIA)] are being considered in China for the national cervical screening program. Comparing risks of CIN3 and cervical cancer (CIN3+) for different results can inform test choice and management guidelines. We evaluated the immediate risk of CIN3+ for different screening results generated from individual and combined tests. We compared tests using a novel statistic designed for this purpose called Mean Risk Stratification (MRS), in a pooled analysis of 17 cross sectional population‐based studies of 30,371Chinese women screened with all 3 methods and diagnosed by colposcopically‐directed biopsies. The 3 tests combined powerfully distinguished CIN3+ risk; triple‐negative screening conferred a risk of 0.01%, while HPV‐positive HSIL+ that was VIA‐positive yielded a risk of 57.8%. Among the three screening tests, HPV status most strongly stratified CIN3+ risk. Among HPV‐positive women, cytology was the more useful second test. In HPV‐negative women, the immediate risks of CIN3+ ranged from 0.01% (negative cytology), 0.00% (ASC‐US), 1.1% (LSIL), to 6.6 (HSIL+). In HPV‐positive women, the CIN3+ risks were 0.9% (negative cytology), 3.6% (ASC‐US), 6.3% (LSIL) and 38.5% (HSIL+). VIA results did not meaningful stratify CIN3+ risk among HPV‐negative women with negative or ASC‐US cytology; however, positive VIA substantially elevated CIN3+ risk for all other, more positive combinations of HPV and cytology compared with a negative VIA. Because all 3 screening tests had independent value in defining risk of CIN3+, different combinations can be optimized as pragmatic strategies in different resource settings.     

Comparison of visual inspection with acetic acid and cervical cytology to detect high-grade cervical neoplasia among HIV-infected women in India

Human immunodeficiency virus (HIV)-infected women in India and other developing country settings are living longer on antiretroviral therapy, yet their risk for human papillomavirus (HPV)-induced cervical cancer remains unabated because of lack of cost-effective and accurate secondary prevention methods. Visual inspection after application of dilute acetic acid on the cervix (VIA) has not been adequately studied against the current standard: conventional cervical cytology (Pap smears) among HIV-infected women. We evaluated 303 nonpregnant HIV-infected women in Pune, India, by simultaneous and independent screening with VIA and cervical cytology with disease ascertainment by colposcopy and histopathology. At the cervical intraepithelial neoplasia (CIN2+) disease threshold, the sensitivity, specificity and positive and negative predictive value estimates of VIA were 80, 82.6, 47.6 and 95.4% respectively, compared to 60.5, 59.6, 22.4 and 88.7% for the atypical squamous cells of undetermined significance or severe (ASCUS+) cutoff on cytology, 60.5, 64.6, 24.8 and 89.4% for the low-grade squamous intraepithelial cells or severe (LSIL+) cutoff on cytology and 20.9, 96.0, 50.0 and 86.3% for high-grade squamous intraepithelial lesion or severe (HSIL+) cutoff on cytology. A similar pattern of results was found for women with the presence of carcinogenic HPV-positive CIN2+ disease, as well as for women with CD4+ cell counts <200 and <350 μL(-1) . Overall, VIA performed better than cytology in this study with biologically rigorous endpoints and without verification bias, suggesting that VIA is a practical and useful alternative or adjunctive screening test for HIV-infected women. Implementing VIA-based screening within HIV/acquired immunodeficiency syndrome care programs may provide an easy and practical means of complementing the highly anticipated low-cost HPV-based rapid screening tests in the near future, thereby contributing to improve program effectiveness of screening.     

Screening for cervical cancer in India: How much will it cost? A trial based analysis of the cost per case detected

The cost and cost effectiveness of screening previously unscreened women by VIA, cytology or HPV testing was investigated within a large cluster randomised trial involving 131,178 women in rural India. All resources involved in implementation, training, management, recruitment, screening and diagnosis were identified and costed. We estimated the total costs and detection rates for each cluster and used these data to calculate an average cluster cost and detection rate for each screening approach. These estimates were combined to estimate a cost per case of cervical intraepithelial neoplasia grade 2/3 or invasive cancer (CIN 2/3+) detected. The average total costs per 1,000 women eligible for screening were US dollar 3,917, US dollar 6,609 and US dollar 11,779 with VIA, cytology and HPV respectively. The cost of detecting a case of CIN2/3+ using VIA was dollar 522 (95% CI dollar 429- dollar 652). Our results suggest that more CIN2/3+ cases would be detected in the same population if cytology were used instead of VIA and each additional case would cost US dollar 1065 (95% CI dollar 713- dollar2175). Delivering cervical cancer screening is potentially expensive in a low-income country although costs might be lower outside a trial setting. We found screening with VIA to be the least expensive option, but it also detected fewer cases of CIN2/3+ than other methods; its long-term cost-effectiveness will depend on the long-term benefits of early detection. Cytology was more effective at detecting cases than VIA but was also more expensive. Our findings indicate that HPV may not be a cost effective screening strategy in India at current consumable prices.     

Performance of visual inspection with acetic acid and human papillomavirus testing for detection of high‐grade cervical lesions in HIV positive and HIV negative Tanzanian women

The aim of this cross sectional study was to assess type distribution of human papillomavirus (HPV) among HIV positive and HIV negative women who underwent cervical cancer screening, and to examine the ability of visual inspection with acetic acid (VIA), the standard detection method in Tanzania, and HPV‐testing to detect cytologically diagnosed high grade lesions or cancer (HSIL+). Women from different areas in Tanzania were invited by public announcement to cervical cancer screening organized by Ocean Road Cancer Institute (Dar‐es‐Salaam). A total of 3,767 women were enrolled. Women underwent gynecological examination with collection of cervical cells for conventional cytological examination, and swab for HPV‐DNA detection (Hybrid‐Capture2) and genotyping (LiPAv2 test). Subsequently VIA was performed. The participants were also tested for HIV. HPV16, HPV52 and HPV18 were the three most common HR HPV types among women with HSIL+ cytology with prevalences of 42.9, 35.7 and 28.6%, respectively, in HIV positive women which was higher than among HIV negative women (30.2, 21.9 and 16.7%). A total of 4.5% of the women were VIA positive, and VIA showed a low sensitivity compared to HPV‐testing for detection of HSIL+. The sensitivity of VIA varied with staff VIA experience, HIV status and age. Vaccines including HPV16, HPV52 and HPV18 will likely reduce the number of HSIL+ cases independently of HIV status. The frequency of HSIL+ was high among HIV positive women, emphasizing the importance of establishing a screening program which also reaches HIV positive women. Our results highlight the importance of continuous training of staff performing VIA, and also point to the need for other screening methods such as HPV‐testing at low cost.     

Test characteristics of visual inspection with 4% acetic acid (VIA) and Lugol's iodine (VILI) in cervical cancer screening in Kerala,India

Simple and inexpensive methods based on visual examination of the cervix are currently being investigated as alternative methods of cervical screening. The test characteristics of visual inspection with 4% acetic acid (VIA), and Lugol's iodine (VILI) and conventional cytology were investigated in a cross-sectional study involving 4,444 women aged 25 to 65 years in Kerala, India. While detection of any acetowhite area constituted a low-threshold positive VIA, detection of well-defined, opaque acetowhite lesions close to or touching the squamocolumnar junction constituted a high-threshold positive VIA test. Detection of definite yellow iodine nonuptake areas in the transformation zone close to or touching the squamocolumnar junction constituted a positive VILI test. Cytology was considered positive if reported as atypia or worse lesions. All screened women were evaluated by colposcopy and biopsies were directed in 1,644 women (37.0%), which allowed the direct estimation of sensitivity, specificity and predictive values. The reference diagnosis was based on a combination of histology and/or colposcopy. True disease status was defined as CIN 2 and worse lesions. A total of 149 (3.4%) women had CIN 2 or worse lesions. The sensitivities of low-threshold VIA, high-threshold VIA, VILI and cytology to detect CIN 2 or worse disease were 88.6%, 82.6%, 87.2% and 81.9%, respectively; the corresponding specificities were 78.0%, 86.5%, 84.7% and 87.8%. Our results indicate that VIA and VILI are suitable alternate screening tests to cytology for detecting cervical neoplasia in low-resource settings.     

Addition of high-risk HPV testing improves the current guidelines on follow-up after treatment for cervical intraepithelial neoplasia

We assessed a possible role for high-risk human papillomavirus (HPV) testing in the policy after treatment for cervical intraepithelial neoplasia (CIN) 2 or 3 (moderate to severe dysplasia). According to the Dutch guidelines follow-up after treatment consists of cervical cytology at 6, 12 and 24 months. Colposcopy is only performed in case of abnormal cervical cytology. In this observational study 184 women treated for CIN 2 or 3 were prospectively monitored by cervical cytology and high-risk HPV testing 3, 6, 9, 12 and 24 months after treatment. Post-treatment CIN 2/3 was present in 29 women (15.8%). A positive high-risk HPV test 6 months after treatment was more predictive for post-treatment CIN 2/3 than abnormal cervical cytology (sensitivity 90% and 62% respectively, with similar specificity). At 6 months the negative predictive value of a high-risk HPV negative, normal smear, was 99%. Largely overlapping, partly different groups of women with post-treatment CIN 2/3 were identified by HPV testing and cervical cytology. Based on these results we advocate to include high-risk HPV testing in monitoring women initially treated for CIN 2/3. In case of a high-risk HPV positive test or abnormal cervical cytology, colposcopy is indicated. All women should be tested at 6 and 24 months after treatment and only referred to the population-based cervical cancer screening programme when the tests are negative on both visits.     

新疆维吾尔族妇女宫颈癌筛查方法横断面比较研究

[目的]探讨适合新疆维吾尔族妇女宫颈癌的筛查方法。[方法]于2006～2007年采用整群抽样方法,选择新疆维吾尔族妇女883名,采用自我采样HPV检测,液基细胞学检查,医生采样HPV检测,肉眼筛查(VIA)进行宫颈癌筛查。分析和比较不同筛查方法的灵敏度、特异度、阳性预测值、阴性预测值。[结果]医师采样HPV检测的灵敏度和特异度均为最高(P<0.01),自我采样的灵敏度与细胞学检查相似(P>0.05),但自我采样HPV检测的特异度高于细胞学检查(P<0.01),与医生采样HPV检测相似(P>0.05)。肉眼筛查的灵敏度和特异度为最低。[结论]新疆维吾尔族妇女的宫颈癌筛查方案应首选医生采样HPV检测,自我采样HPV检测是比较适合于新疆民族地区妇女的方案,在偏远和缺少设备的地区,肉眼筛查也是一种可行的筛查方法。     

4 种不同检查方法在宫颈癌筛查中的临床应用价值*

目的:了解4 种不同检查方法在宫颈癌筛查中的临床应用价值。方法:采用第二代杂交捕获技术（hybrid capture 2,HC-II）检测13种高危型人乳头瘤病毒（human papillomavirus ,HPV ）、薄层液基细胞学技术（Liquid-based cytology test,LCT ）检测宫颈脱落细胞、醋酸肉眼检查（visual inspection with acetic acid,VIA）和阴道镜检查4 种方法对2004年11月～2004年12月深圳南山区华侨城区域15～59岁有性生活女性共1 137 例进行盲法同步宫颈癌筛查。对阴道镜检查异常或可疑异常者行阴道镜下直接活检;对HPV 阳性并且LCT ≥未明确诊断意义的不典型鳞状上皮细胞（atypical squamous cells of undetetemined sign,ASCUS ）,或HPV 阴性但LCT ≥低度鳞状上皮内病变（low grade squamous intraepithelial lesion ,LSIL ）的妇女再次行阴道镜下活组织病理学检查,以病理结果作为验证4种检查方法的金标准。结果:共取病理122 例。病理结果证实该人群中无宫颈癌病例:子宫颈上皮内瘤变（cervical intraepithelial neoplasia ,CIN）Ⅲ级3 例,CIN Ⅱ级11例,CIN Ⅰ级36例;慢性宫颈炎和鳞状上皮化生69例;正常宫颈3 例。人群的高危HPV 总检出率为14.0% ;LCT 阳性率为12.6% ;VIA 阳性率为12.5% ;阴道镜阳性率为13.6% 。随宫颈病变级别升高,高危HPV 感染率及LCT 阳性率均呈趋势性增加（P<0.005）;VIA 和阴道镜阳性率在各级宫颈病变中无统计学差异,但在宫颈病变组阳性检出率明显高于正常宫颈组。高危HPV 对宫颈高度病变的敏感性、特异性、准确性、阳性预测值、阴性预测值、阳性似然比和阴性似然比分别为100% 、87.1% 、87.3% 、8.8% 、100% 、7.6% 和0;LCT 以上各指标分别为92.9% 、88.4% 、88.5% 、9.1% 、99.9% 、8.0% 和8.0% ;VIA 以上各指标分别为35.7% 、96.0% 、95.3% 、10.0% 、99.2% 、8.9% 和67.0% ;阴道镜以上各指标分别为50.0% 、86.8% 、86.4% 、4.5% 、99.3% 、3.8% 和58.0% 。结论:高危HPV 检测和LCT 检查均为目前宫颈癌筛查较好的方法,VIA 和阴道镜检查敏感性较差,漏诊率高,不适合大范围筛查,但二者阴性预测值均较高,可应用于临床病例诊断。      

Visual inspection with acetic acid for detection of high grade lesion in atypical squamous cells and low grade squamous intraepithelial lesions from cervical Pap smear

Objective

To evaluate the value of visual inspection with acetic acid (VIA) test to detect high grade lesion in women with atypical squamous cells or low grade squamous intraepithelial lesions cervical cytology.

Methods

Women with atypical squamous cells or low grade squamous intraepithelial lesions who were scheduled to undergo colposcopy at Vajira Hospital and met inclusion criteria were included. All participants underwent VIA test prior to usual steps of colposcopy. The VIA results were interpreted as positive or negative using the criteria by the International Agency for Cancer Research. The standard colposcopic examination and appropriate investigations for cervical pathology were then continued. The diagnostic values of VIA test including sensitivity, specificity, positive predictive value, and negative predictive value were determined using high grade lesion including cervical intraepithelial neoplasia 2-3 and squamous cell carcinoma as a threshold.

Results

Total of 106 women was included. The VIA test was positive in 33 women (31.1%) and negative in 73 women (68.9%). Among the women with VIA test positive, 14 had high grade lesion (42.4%) while 19 had no significant lesions. Only 2/73 (2.7%) cases with negative VIA test had high grade lesion (both had cervical intraepithelial neoplasia 2). The sensitivity, specificity, positive predictive value and negative predictive value with 95% confidence interval were 87.5% (81.2 to 93.8%), 78.8% (71.1 to 86.7%), 42.4% (33.0 to 51.8%), and 97.2% (94.2 to 1.0%) respectively.

Conclusion

VIA as the intermediate test in atypical squamous cells and low grade squamous intraepithelial lesions cytology may reduce the necessity to refer some women for colposcopy.     

Neither one‐time negative screening tests nor negative colposcopy provides absolute reassurance against cervical cancer

A population sample of 10,049 women living in Guanacaste, Costa Rica, was recruited into a natural history of human papillomavirus (HPV) and cervical neoplasia study in 1993–1994. At the enrollment visit, we applied multiple state‐of‐the‐art cervical cancer screening methods to detect prevalent cervical cancer and to prevent subsequent cervical cancers by the timely detection and treatment of precancerous lesions. Women were screened at enrollment with 3 kinds of cytology (often reviewed by more than one pathologist), visual inspection and cervicography. Any positive screening test led to colposcopic referral and biopsy and/or excisional treatment of CIN2 or worse. We retrospectively tested stored specimens with an early HPV test (hybrid capture tube test) and for >40 HPV genotypes using a research PCR assay. We followed women typically 5–7 years and some up to 11 years. Nonetheless, 16 cases of invasive cervical cancer were diagnosed during follow‐up. Six cancer cases were failures at enrollment to detect abnormalities by cytology screening; 3 of the 6 were also negative at enrollment by sensitive HPV DNA testing. Seven cancers represent failures of colposcopy to diagnose cancer or a precancerous lesion in screen‐positive women. Finally, 3 cases arose despite attempted excisional treatment of precancerous lesions. Based on this evidence, we suggest that no current secondary cervical cancer prevention technologies applied once in a previously under‐screened population is likely to be 100% efficacious in preventing incident diagnoses of invasive cervical cancer. © 2009 UICC     

Visual inspection as a cervical cancer screening method in a primary health care setting in Africa

We evaluated the feasibility and performance of visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) for cervical cancer screening in a primary health-care setting in Kinshasa, Congo. Women (1,528) aged > or =30 years were screened independently by nurses and physicians by VIA and VILI and Pap cytology. Biopsy samples were obtained from women with abnormal colposcopies and from 290 randomly chosen women with normal colposcopy. Cytological and histological examinations were performed in Lyon and Montreal, respectively. The prevalence of cervical intraepithelial neoplasia (CIN) of grades 1, 2 and 3 was 4.5, 1.3 and 4%, respectively. Using biopsy as the reference, the sensitivity, specificity and negative predictive value (NPV) for > or =CIN 2 for VIA-nurse were 55.5% (95% CI: 34.7-76.2), 64.6% (95% CI: 62.0-67.1) and 96.8% (95% CI: 93.5-98.7), respectively. The corresponding values for VILI-nurse were 44.0% (95% CI: 24.2-63.8), 74.6% (95% CI: 72.3-76.9) and 96.7% (95% CI: 93.7-98.6). The equivalent parameters for physicians were 71.1% (95% CI: 46.7-95.5), 71.3% (95% CI: 68.9-73.6) and 98.6% (95% CI: 96.0-99.7) for VIA and 68.3% (95% CI: 42.5-94.0), 76.2% (95% CI: 74.0-78.4) and 97.2% (95% CI: 95.3-98.5) for VILI. The sensitivity of cytology ranged between 31 and 72%, depending on the abnormality threshold used to define positivity, with a corresponding specificity range of 94-99% and a NPV range of 97-99%. Our results show that VIA and VILI performed by nurses and physicians are slightly more sensitive but less specific than Pap cytology across multiple combinations of test and lesion thresholds. Given their lower cost and easy deployment, visual inspection methods merit further assessment as cervical cancer screening methods for low-resource countries.