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.     

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.     

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.     

Comparison between Visual Inspection of Cervix and Cytology Based Screening Procedures in Bangladesh

Background: Cervical cancer continues to be a major problem in Bangladesh with approximately 18,000 newcases annually of which over 10,000 women die from it. Visual inspection of the cervix after 3-5% acetic acid(VIA) application is a simple and easy to learn method for cervical cancer screening, although cytology-basedscreening is more often applied in developed countries where it has successfully reduced the prevalence of cervicalcancer. Objective: To compare the efficacy of VIA and cytology-based primary methods for cervical cancerscreening in Bangladesh. Materials and Methods: This hospital based comparative study was conducted at theVIA centre and Colposcopy Clinic of Bangabandhu Sheikh Mujib Medical University (BSMMU) from October2008 to October 2010. Results: Among 650 women, 74 (11.4%) were VIA+ve and 8 (1.2%) had abnormalitiesin their Pap smear reports. During colposcopy, 38 (7.7%) women had different grades of CIN and 4 (0.6%)had cervical cancer. The gold standard histology findings proved 20 women had CIN I, 14 had CIN II/II and 4had cervical cancer. Among the 38 histology diagnosed abnormalities, VIA test could identify 30 abnormalitiesincluding two cervical cancers. However, Pap smear could detect only 8 cases of histological abnormalities (2low grade and 6 had high grade lesion) and it missed all the cervical cancer cases. The sensitivity and specificityof VIA were 88.9% and 52.1%. The positive predictive value (PPV) and negative predictive value (NPV) were41.0%, and 92.6% respectively. Moreover, the sensitivity, specificity, PPV and NPV of Pap smear were 33.3%,95.8%, 75.0% and 79.3%, respectively. Conclusions: VIA test should be used as the primary screening tool evenwith its low sensitivity and specificity in low resource countries like Bangladesh. False positive results may begreater, but overtreatment can be minimized by colposcopy evaluation of the VIA positive women.     

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. ‍     

醋酸染色肉眼观察在子宫颈癌筛查分流中的应用价值

目的:评价醋酸染色肉眼观察(VIA)在宫颈癌筛查中分流自我取样人乳头瘤病毒(HPV) DNA阳性人群的可行性及应用价值.方法:对2 500名河南省新密市25～65岁的妇女进行宫颈癌筛查.初次访视时每位妇女均接受了自我取样HPV DNA检测和VIA.任何筛查阳性及随机10％阴性的妇女进行第2次VIA和阴道镜检查.阴道镜下可见病变处直接活检;无可见病变但筛查阳性时行四象限随机活检+宫颈管搔刮术(ECC).以病理诊断为金标准.结果:最终有2 463名妇女纳入分析.目标人群自我取样HPV的阳性率为17.3％(427/2 463),检出CINⅡ+的灵敏度为89.2％(33/37),特异度为83.8％(2 032/2 426),阳性预测值(PPV)为7.7％(33/427).用VIA对自我取样HPV DNA阳性者进行分流,阴道镜转诊率由17.3％(427/2 463)降至2.5％(61/2 463),x2=304.7,P＜0.001;特异度和PPV可分别达到98.3％(2 384/2 426)(x2=350.0,P＜0.001)和31.2％(19/61),x2=30.7,P＜0.001,灵敏度为51.4％.结论:用VIA分流自我取样HPV DNA阳性妇女,可以显著提高宫颈癌筛查的特异度和PPV值,明显降低阴道镜转诊率,对于未绝经妇女,意义更为显著.这种分流方法可以有效节约卫生资源,有望成为宫颈癌筛查分流的一种新选择.     

Performance of visual inspection of the cervix with acetic acid (VIA) for triage of HPV screen-positive women: results from the ESTAMPA study

VIA is recommended for triage of HPV-positive women attending cervical screening. In the multicentric ESTAMPA study, VIA performance for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among HPV-positive women was evaluated. Women aged 30-64 years were screened with HPV testing and cytology and referred to colposcopy if either test was positive. At colposcopy visit, study-trained midwives/nurses/GPs performed VIA ahead of colposcopy. VIA was considered positive if acetowhite lesions were observed in or close to the transformation zone. Ablative treatment eligibility was assessed for VIA positives. Performance indicators were estimated. Three thousand one hundred and forty-two HPV-positive women were included. Sensitivity for CIN3+ was 85.9% (95% CI 81.2-89.5) among women <50 years and, although not significant, slightly lower in women 50+ (78.0%, 95% CI 65.9-86.6). Overall specificity was 58.6% (95% CI 56.7-60.5) and was significantly higher among women 50+ (70.3%, 95% CI 66.8-73.5) compared to women <50 (54.3%, 95% CI 52.1-56.5). VIA positivity was lower among women 50+ (35.2%, 95% CI 31.9-38.6) compared to women <50 (53.2, 95% CI 51.1-55.2). Overall eligibility for ablative treatment was 74.5% and did not differ by age. VIA sensitivity, specificity, and positivity, and ablative treatment eligibility varied highly by provider (ranges: 25%-95.4%, 44.9%-94.4%, 8.2%-65.3%, 0%-98.7%, respectively). VIA sensitivity for cervical precancer detection among HPV-positive women performed by trained providers was high with an important reduction in referral rates. However, scaling-up HPV screening triaged by VIA will be challenging due to the high variability of VIA performance and providers' need for training and supervision.     

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。     

Diagnostic accuracy of VIA and HPV detection as primary and sequential screening tests in a cervical cancer screening demonstration project in India

Visual inspection after acetic acid application (VIA) and human papillomavirus (HPV) detection tests have been recommended to screen women for cervical cancer in low and middle income countries. A demonstration project in rural India screened 39,740 women with both the tests to compare their accuracies in real population setting. The project also evaluated the model of screening women in the existing primary health care facilities, evaluating the screen positive women with colposcopy (and biopsy) in the same setup and recalling the women diagnosed to have disease for treatment at tertiary center. Accuracy of VIA and HPV test used sequentially was also studied. VIA was performed by trained health workers and Hybrid Capture II (HC II) assay was used for oncogenic HPV detection. Test positivity was 7.1% for VIA and 4.7% for HC II. Detection rate of CIN 3+ disease was significantly higher with HC II than VIA. Sensitivities of VIA and HC II to detect 162 histology proved CIN 3+ lesions were 67.9 and 91.2%, respectively after adjusting for verification bias. Specificity for the same disease outcome and verification bias correction was 93.2% for VIA and 96.9% for HC II. Triaging of VIA positive women with HPV test would have considerably improved the positive predictive value (4.0 to 37.5% to detect CIN 3+) without significant drop in sensitivity. All VIA positive women and 74.0% of HC II positive women had colposcopy. There was high compliance to treatment and significant stage‐shift of the screen‐detected cancers towards more early stage.     

宫颈癌多种筛查方案的研究

目的 探索适宜我国不同地区的宫颈癌筛查方案,以提高我国妇女宫颈癌的防治水平.方法 利用1999年在山西省襄垣县开展的一项以人群为基础的宫颈癌筛查横断面研究的资料,所有筛查对象均进行了薄层液基细胞学(LBC)、荧光镜检、醋酸染色法(VIA)、阴道镜检查、自我取样人乳头瘤病毒(HPv)检测和医生取样HPV检测等6种宫颈癌筛查方法 ,而且每位筛查对象均有病理诊断结果 .采用筛查试验的串、并联法组合各种筛查技术,比较所得方案识别宫颈高度以上病变[≥宫颈上皮内瘤变(CIN)2]的灵敏度、特异度和阴道镜转诊率等指标,以受试者工作特征曲线(ROC)下面积综合分析各筛查方案.结果 LBC检测以未明确意义的不典型鳞状细胞(ASC-US)为阳性,HPV检测以HPV DNA≥1.0 ps/mi为阳性.在LBC和HPV检测组合方案中,并联初筛方法 (即两者任一项阳性即判断为筛查阳性)的灵敏度为100.O%,特异度为68.6%,阴道镜转诊率为34.4%;LBC初筛HPV分流方法 (即ASC-US者进行HPV检测)的灵敏度为93.0%,特异度为89.9%,阴道镜转诊率为13.7%;HPV初筛LBC分流方法 (即 HPV阳性者进行LBC检测)的灵敏度为91.7%,特异度为93.0%,阴道镜转诊率为10.6%.经ROC分析,LBC初筛HPV分流方法 和HPV初筛LBC分流方法 明显优于单纯并联初筛方法 (P=0.0003;P=0.0002).单独以LBC或HPV检测作为筛查方案时,以ASC-US或低度病变(LSIL)为筛查阳性的LBC方法 灵敏度、特异度和阴道镜转诊率分别为94.2%、77.3%、25.7%和87.2%、93.5%、10.O%;医生取样HPV检测方法 和自我取样HPV检测方法 的灵敏度、特异度和阴道镜转诊率分别为97.6%、84.8%、18.8%和83.5%、85.9%、17.1%.经ROC分析,医生取样HPV检测方法 优于以ASC-US为筛查阳性的LBC方法 或自我取样HPV检测方法 (P=0.005,P=0.002).在VIA及其与HPV检测的组合方案中,单独采用VIA筛查方法 的灵敏度为70.9%,特异度为74.3%,阴道镜转诊率为27.6%;HPV初筛VIA分流方法 (即自我取样HPV检测阳性者进行VIA检查)的灵敏度、特异度和阴道镜转诊率分别为65.9%、95.2%和7.4%.经ROC分析,HPV初筛VIA分流方法 明显优于单独使用VIA方法 (P=0.004).结论 根据地区资源条件和个人意愿,我国经济发达地区可选用HPV初筛LBC分流方法 或LBC初筛HPV分流方法 作筛查手段;中等经济发展水平的中小城市可选用单独以LBC或HPV检测方法 作为筛查手段;VLA是欠发达地区可行的筛查方法 ,在廉价HPV检测试剂盒上市后,可选择HPV初筛VIA分流方法 ,以进一步提高宫颈癌的筛查效力.     

新型国产杂交捕获HPV检测技术在ASC-US人群分流中的应用效果评价

目的 探讨基于杂交捕获原理的DH2检测技术在未明确意义的不典型鳞状细胞(Atypical squamous cells of undetermined significance,ASC-US)人群中的分流应用效果.方法 本研究于2016年10月—2018年10月在河南省新密市招募21～64岁普通女性参加研究.所有女性在...     

Pooled analysis of the accuracy of five cervical cancer screening tests assessed in eleven studies in Africa and India

Cervical cancer is the main cancer among women in sub-Saharan Africa, India and other parts of the developing world. Evaluation of screening performance of effective, feasible and affordable early detection and management methods is a public health priority. Five screening methods, naked eye visual inspection of the cervix uteri after application of diluted acetic acid (VIA), or Lugol's iodine (VILI) or with a magnifying device (VIAM), the Pap smear and human papillomavirus testing with the high-risk probe of the Hybrid Capture-2 assay (HC2), were evaluated in 11 studies in India and Africa. More than 58,000 women, aged 25-64 years, were tested with 2-5 screening tests and outcome verification was done on all women independent of the screen test results. The outcome was presence or absence of cervical intraepithelial neoplasia (CIN) of different degrees or invasive cervical cancer. Verification was based on colposcopy and histological interpretation of colposcopy-directed biopsies. Negative colposcopy was accepted as a truly negative outcome. VIA showed a sensitivity of 79% (95% CI 73-85%) and 83% (95% CI 77-89%), and a specificity of 85% (95% CI 81-89%) and 84% (95% CI 80-88%) for the outcomes CIN2+ or CIN3+, respectively. VILI was on average 10% more sensitive and equally specific. VIAM showed similar results as VIA. The Pap smear showed lowest sensitivity, even at the lowest cutoff of atypical squamous cells of undetermined significance (57%; 95% CI 38-76%) for CIN2+ but the specificity was rather high (93%; 95% CI 89-97%). The HC2-assay showed a sensitivity for CIN2+ of 62% (95% CI 56-68%) and a specificity of 94% (95% CI 92-95%). Substantial interstudy variation was observed in the accuracy of the visual screening methods. Accuracy of visual methods and cytology increased over time, whereas performance of HC2 was constant. Results of visual tests and colposcopy were highly correlated. This study was the largest ever done that evaluates the cross-sectional accuracy of screening tests for cervical cancer precursors in developing countries. The merit of the study was that all screened subjects were submitted to confirmatory investigations avoiding to verification bias. A major finding was the consistently higher sensitivity but equal specificity of VILI compared with VIA. Nevertheless, some caution is warranted in the interpretation of observed accuracy measures, since a certain degree of gold standard misclassification cannot be excluded. Because of the correlation between visual screening tests and colposcopy and a certain degree of over-diagnosis of apparent CIN2+ by study pathologists, it is possible that both sensitivity and specificity of VIA and VILI were overestimated. Gold standard verification error could also explain the surprisingly low sensitivity of HC2, which contrasts with findings from other studies.     

Effectiveness of novel,lower cost molecular human papillomavirus‐based tests for cervical cancer screening in rural china

This study examined the efficacy of the OncoE6? Cervical Test, careHPV? and visual inspection with acetic acid (VIA) in identifying women at risk for cervical cancer and their capability to detect incident cervical precancer and cancer at 1‐year follow‐up. In a population of 7,543 women living in rural China, women provided a self‐collected and two clinician‐collected specimens and underwent VIA. All screen positive women for any of the tests, a ～10% random sample of test‐negative women that underwent colposcopy at baseline, and an additional ～10% random sample of test‐negative women who did not undergo colposcopy at baseline (n = 3,290) were recruited. 2,904 women were rescreened 1 year later using the same tests, colposcopic referral criteria, and procedures. Sensitivities of baseline tests to detect 1‐year cumulative cervical intraepithelial neoplasia Grade 3 or cancer (CIN3+) were 96.5% and 81.6% for careHPV? on clinician‐collected and self‐collected specimens, respectively, and 54.4% for OncoE6? test. The OncoE6? test was very specific (99.1%) and had the greatest positive predictive value (PPV; 47.7%) for CIN3+. Baseline and 1‐year follow‐up cervical specimens testing HPV DNA positive was sensitive (88.0%) but poorly predictive (5.5–6.0%) of incident CIN2+, whereas testing repeat HPV16, 18 and 45 E6 positive identified only 24.0% of incident CIN2+ but had a predictive value of 33.3%. This study highlights the different utility of HPV DNA and E6 tests, the former as a screening and the latter as a diagnostic test, for detection of cervical precancer and cancer.     

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.     

Accuracy of Visual Inspection with Acetic acid in Detecting High-Grade Cervical Intraepithelial Neoplasia in Pre- and Post-Menopausal Thai Women with Minor Cervical CytologicalAbnormalities

Purpose: To determine the accuracy of visual inspection with acetic acid (VIA) in detecting high-gradecervical intraepithelial neoplasia (CIN) in pre- and post-menopausal women with atypical squamous cells ofundetermined significance (ASC-US) and low grade squamous intraepithelial lesion (LSIL) Papanicolaou (Pap)smears. Materials and Methods: Two hundred women (150 pre-menopausal and 50 post-menopausal) with ASCUSand LSIL cytology who attended the colposcopy clinic, Thammasat University Hospital, between March 2013and August 2014 were included. All women underwent VIA testing and colposcopy by gynecologic oncologists.Diagnostic values of VIA testing including sensitivity, specificity, positive predictive value (PPV) and negativepredictive value (NPV) for detecting high-grade CIN were determined using the histopathology obtained fromcolposcopic-directed biopsy as a gold standard. Results: VIA testing was positive in 54/150 (36%) pre-menopausalwomen and 5/50 (10%) post-menopausal women. Out of 54 pre-menopausal women with positive VIA testing,15 (27.8%) had high-grade CIN and 39 (72.2%) had either CIN 1 or insignificant pathology. Ten (10.4%), 43(44.8%) and 43 (44.8%) out of the remaining 96 pre-menopausal women with negative VIA testing had highgradeCIN, CIN 1 and insignificant pathology, respectively. Out of 5 post-menopausal women with positive VIAtesting, there were 4 (80%) women with high-grade CIN, and 1 (20%) women with insignificant pathology. Outof 45 VIA-negative post-menopausal women, 42 (93.3%) women had CIN 1 and insignificant pathology, and 3(6.7%) had high-grade CIN. Sensitivity, specificity, PPV and NPV of the VIA testing were 59.4%, 76.2%, 32.2%and 90.8%, respectively (60%, 68.8%, 27.8% and 89.6% in pre-menopausal women and 57.1%, 97.7%, 80%and 93.3% in post-menopausal women). Conclusions: VIA testing may be used as a screening tool for detectinghigh-grade CIN in women with minor cervical cytological abnormalities in a low-resource setting in order tolower the rate of colposcopy referral.     

Cervical Cancer Screening by Visual Inspection with AceticAcid- Interobserver Variability between Nurse and Physician

Objectives: The objective of the study was to evaluate and compare the test performance of visual inspectionwith acetic acid (VIA) by a physician and nurse so as to evaluate the feasibility and efficacy of training a nursein interpreting VIA. Methods: It was a cross sectional study conducted in the colposcopy clinic at the Universityteaching hospital. 406 women who fulfilled the selection criteria underwent VIA done by both physician andnurse and the findings were interpreted independently. This was followed by colposcopy done by a gynecologistblinded to the results of VIA and directed biopsy was taken if indicated. The diagnostic efficacy was calculatedseparately for physician and nurse using threshold of cervical intraepithelial neoplasia (CIN) 2 and above andconcordance of results between the physician and nurse was determined by kappa statistics. Results: VIA byphysician had a higher sensitivity (88.89% versus 80%) and a higher specificity (69.81% versus 54.85%) withdisease threshold of CIN 2 and above. The concordance of results showed moderate agreement (kappa=0.366).Conclusion: Trained nurses can be an effective alternative human resource for cervical cancer screening usingVIA as a preliminary screening method. Intensive training and periodic reinforcement sessions are needed soas to reduce the false positive results.     

Evaluation of oncogenic human papillomavirus RNA and DNA tests with liquid-based cytology in primary cervical cancer screening: the FASE study

The APTIMA HPV Assay (AHPV) allows detection of 14 high-risk human papillomavirus (HPV) RNA types in cervical specimens. Until present, the assay has been compared to HPV DNA tests only in triage settings. Herein, we compare AHPV with a DNA assay (Hybrid Capture 2; HC2) and liquid-based cytology (LBC; using PreservCyt ThinPrep liquid Pap) in a screening setting (French APTIMA screening evaluation [FASE] study). Women (N = 5,006) aged 20-65 were screened by gynecologists in 17 private practices in Paris, France. One cervical specimen was collected and tested with LBC, AHPV and HC2 assays. Women were referred to colposcopy if they were ASC-US+ in LBC or HPV positive in either HPV assay. To control for verification bias, a random group (14%) with normal LBC and dually HPV negative tests underwent colposcopy. Data from 4,429 women were analyzed. Sensitivity, specificity and predictive values were calculated for the three tests. AHPV and HC2 were highly sensitive for CIN2+ (92.0% and 96.7%) and CIN3+ (95.7% and 95.3%) detection and much more sensitive than LBC (69.1% for CIN2+ and 73.3% for CIN3+). Specificity of AHPV was higher than that of HC2, but similar to that of LBC (p < 0.001). Combining LBC with either HPV test slightly increased sensitivity but compromised specificity. AHPV assay is both specific and sensitive for the detection of high-grade precancerous lesions and may be considered as an option for routine cervical cancer screening for women over 20 years of age.     

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.     

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.     

Effectiveness of a two‐stage strategy with HPV testing followed by visual inspection with acetic acid for cervical cancer screening in a low‐income setting

The World Health Organization recently advocated a two‐stage strategy with human papillomavirus (HPV) testing followed by visual inspection of the cervix with acetic acid (VIA) as a suitable option for cervical cancer screening. However, its accuracy has never been directly assessed in the context of primary screening. To evaluate effectiveness of HPV testing on self‐obtained specimens (self‐HPV) followed by VIA (sequential testing) in a low‐income setting, we recruited 540 women aged between 30 and 65 years in two Cameroonian periurban areas. Eligible women were counseled about cervical cancer and how to perform self‐sampling. HPV positive and a random sample of HPV‐negative women were called back for VIA and biopsy. Disease was defined by interpretation of cervical intraepithelial neoplasia Grade 2 or worse (CIN2+). Performances of VIA, self‐HPV and sequential testing were determined after adjustment for verification bias. HPV prevalence was 27.0%. VIA positivity was 12.9% and disease prevalence was 5%. Sensitivity and specificity of VIA for CIN2+ were 36.4% [95% confidence interval (CI): 15.2–64.6%] and 90.4% (95% CI: 85.4–93.7%), respectively. Sensitivity of self‐HPV [100.0% (95% CI: 79.6–100.0%)] was 66% higher than that of sequential testing [33.3% (95% CI: 15.2–58.3%)]. Meanwhile, specificity of self‐HPV [74.5% (95% CI: 70.6–78.1%)] was 22% lower than that of sequential testing [96.7% (95% CI: 94.8–97.9%)]. A two‐stage screening strategy with self‐HPV followed by VIA improves specificity of cervical cancer screening, but at the cost of an important loss of sensitivity. Ways to improve VIA performance or other tools are needed to increase positive predictive value of HPV testing.