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.     

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.     

VIA-VILI结合电子阴道镜检随访筛查早期发现宫颈病变

目的 在宫颈癌高发区通过对高危人群实施跟踪随访筛查以达到宫颈癌早期诊断和早期治疗。方法 对目标人群的30~59岁适龄妇女应用醋染（VIA）和碘染（VILI）进行初筛,结合子阴道镜检和病理检查进而明确诊断。结果 2006~2007年共筛查5595人,随访检查3676人,最终病理诊断结果证实CIN Ⅰ189例,CIN Ⅱ25例,CIN Ⅲ/原位癌19例,宫颈浸润癌8例。结论 碘染、醋染作为宫颈癌的初筛方法其符合率分别为41.6%和64%,但结合阴道镜及镜下定位活检病理检查可大大提高宫颈癌癌前病变及早期宫颈癌的诊断率。     

2006-2009年山西省襄垣县VIA/VILI筛查宫颈癌的检出效果评价

目的：通过对2006—2009年山西省襄垣县宫颈癌筛查早诊早治结果分析,评价醋酸或碘染色肉眼观察法（visual inspection with acetic acid/Lugol’s iodine,VIA/VILI）宫颈癌筛查方案在农村高发区推广应用的可行性。方法2006—2009年在山西省襄垣县对30~59岁的妇女进行宫颈癌筛查。用VIA和VILI作为初筛方法,VIA/VILI阳性者进行阴道镜检查,阴道镜异常者在病变处取活检进行病理诊断。对VIA和VILI阴性、VIA/VILI阳性但阴道镜检查正常、VIA/VILI阳性同时阴道镜检查异常且病理活检结果为轻度宫颈上皮内瘤样病变（cervical intraepithelial neoplasia grade 1,CIN1）或正常的妇女一年后用与初筛同样的方法进行复查。结果2006—2010年累计筛查16703人次,其中初筛9618人,复查7085人。4年初筛人群累计阴道镜转诊率、中度CIN及以上（CIN2+）检出率、重度CIN及以上（CIN3+）检出率分别为4.6%（438/9618）、0.9%（82/9618）、0.5%（44/9618）;复查人群上述指标分别为3.1%（221/7085）、0.6%（42/7085）、0.2%（19/7085）;筛查人群累计（包括初筛和复查）上述指标分别为4.0%（659/16703）、1.3%（124/9618）、0.7%（63/9618）。初筛人群阴道镜转诊率、CIN2+检出率和CIN3+检出率均随方案的持续开展呈升高趋势（P<0.001）;复查阴道镜转诊率、CIN2+检出率则呈下降趋势（P<0.001）。结论随着VIA/VILI筛查方案在示范基地的推广,筛查效果越来越显著。VIA/VI-LI是一种经济有效的宫颈癌及其癌前病变筛查方法,适宜在资源有限、经济欠发达的农村地区推广。持续的培训和实践是VIA/VILI筛查方案有效实施的关键措施。     

山西省襄垣县2009~2015年农村女性宫颈癌筛查项目结果分析

[目的]通过分析襄垣县2009～2015年农村妇女宫颈癌筛查结果,为国家宫颈癌筛查项目的评价和优化提供理论依据.[方法]对襄垣县35～64岁妇女开展宫颈癌筛查.2009～2013年采用醋酸/碘染色后肉眼观察(VIA/VILI),2014年开始部分引入人乳头状瘤病毒(HPV)检测,2015年又引入新柏氏液基细胞学(TCT)检测,根据卫生资源情况在不同人群中分别使用三种方法.任意筛查结果阳性者转诊阴道镜,镜下有病变时取活检,以病理诊断为金标准.通过评价不同方法对宫颈上皮内瘤变(CIN)2级及以上病变的检出率评价不同方法对宫颈癌的筛查效果.[结果] 2009～2015年共筛查62 618名女性,其中CIN2级及以上(CIN2+)病变的患病率为0.76％,早诊率为90.53％,下生殖道感染率为25.68％,其中滴虫性阴道炎、细菌性阴道炎和宫颈炎与HPV感染相关.根据2014及2015年数据,VIA/VILI的CIN2+病变检出率为0.74％,TCT的病变检出率为0.70％,两者相似,但均低于HPV检测,其病变检出率为1.37％.[结论]HPV检测是首选的宫颈癌初筛方法,在资源匮乏地区,培训合格的基层医生使用VIA/VILI或TCT方法对适龄妇女开展宫颈癌筛查是有效的备选方案.     

醋酸涂抹法在宫颈癌筛查中的应用价值

背景与目的：目前,宫颈癌发病率在我国一些经济落后地区仍较高。原因之一是在这些地区难以开展宫颈细胞学涂片检查宫颈癌的普查工作。本研究通过分析应用醋酸涂抹法检测宫颈上皮内瘤样病变(cervical intraepithelial neoplasia,CIN)及宫颈癌的敏感性和特异性,从而评价其在宫颈癌筛查中的应用价值。方法：对山西省襄垣县年龄为35-45岁的1997名妇女进行宫颈癌普查,首先应用5％醋酸涂抹法,同时对每名妇女均进行高危型人乳头状瘤病毒(human papillomavirua,HPV)DNA的检查、液基细胞学及阴道镜检查,在阴道镜下对病变区或每个正常象限的宫颈鳞柱上皮交界处的2、4、8、10点取活检,并行宫颈管刮出物病检,病理检查结果为金标准。结果：病理检查证实CINⅡ级43例,CINⅢ级31例,宫颈浸润癌12例。2例妇女仅颈管刮出物阳性,其中l例为CINⅡ级,另l例为CINⅢ级。醋酸涂抹法诊断结果为：正常1445例(72．4％),低度病变525例(26．3％),高度病变2l例(1．0％),宫颈癌6例(0．3％)。醋酸涂抹法诊断为低度病变或其以上病变者中,经病理检查证实为CINⅡ级及其以上病变的检出敏感性为70．9％(6l／86),特异性为74．3％(1420／1911),对小病灶的敏感性为64．9％(37／57),而大的病灶达88．9％(24／27)。阴道镜对高度病变的检出率为8l.4％(70／86),特异性为76．5％(1462／1911)。结论：醋酸涂抹法具有较高的特异性和敏感性。对CINⅡ级及其以上病变,醋酸涂抹法和阴道镜检查具有相似的特异性。由于醋酸涂抹法简便、费用低廉,对于经济落后地区不失为宫颈癌筛查中一种有效可行的初筛方法。     

Comparing PAP smear cytology, aided visual inspection, screening colposcopy, cervicography and HPV testing as optional screening tools in Latin America. Study design and baseline data of the LAMS study

OBJECTIVES: This is a European Commission (EC)-funded ongoing study known as the LAMS (Latin American Screening) study, where PAP smear/liquid-based cytology and screening colposcopy were compared with i) three optional screening tools [visual inspection with acetic acid (VIA), or Lugol's iodine (VILI), cervicography] and with ii) Hybrid Capture II from a) conventional samples and from b) self-samples, in women at different risk for cervical cancer in Brazil and Argentina. STUDY DESIGN: During 2002-2003, a cohort of 12,107 women attending four clinics: Campinas (CA), Sao Paulo (SP), Porto Alegre (PA) and Buenos Aires (BA), were interviewed for risk factors, and examined using the 8 diagnostic arms. Colposcopy was performed for women positive in any test and for 5% of women with baseline PAP-negative and 20% of HCII-negatives. All high-grade lesions (CIN2/3) were treated, and low-grade CIN are prospectively followed-up. RESULTS: Of the 12,107 women, the following baseline data are available: epidemiological data (n=11,996), conventional PAP smears (n=10,363), LBC, SurePATH (n=320), LBC, DNA-Citoliq (n=1,346), VIA (n=12.067), VILI (n=3,061), cervicography (n=279), screening colposcopy (n=3,437), HCII conventional (n=4,710), HCII self-sampling (n=246) and cervical biopsies (n=1,524). The four sub-cohorts differ significantly in all their baseline data on the implicated risk factors of cervical cancer, consonant with their origin from regions with different cancer incidence. Around 95% of all PAP smears were negative, with slight variations in the prevalence of LSIL and HSIL between the four centers. Significant differences were found in the detection rates of abnormal findings in VIA, VILI and colposcopy between the four centers (p=0.0001). The prevalence of HPV was practically identical (16.5-18.8%) in all four cohorts (p=0.486), with no differences in the relative viral loads. Biopsy results were different depending on whether the women underwent screening colposcopy (BA) or elective colposcopy (others). CONCLUSION: Four cohorts with significantly different baseline data are available, and prospective follow-up of these women permits analysis of whether variations in cervical cancer incidence in these regions is due to i) different natural history of the precursor lesions, or ii) due to different levels of exposure to the known risk factors.     

Inappropriate gold standard bias in cervical cancer screening studies

As acetic acid-aided visual inspection (VIA) and colposcopic-directed biopsy miss small >/=cervical intraepithelial neoplasia (CIN) 2, inflation of sensitivity of VIA may occur when colposcopic-directed biopsy is the gold standard for >/=CIN 2. To determine whether such inflation occurs, we reviewed 375 women with >/=CIN 2 from the Shanxi Province Cervical Cancer Screening Study II. These women had positive self or physician-collected tests for high-risk human papillomavirus or abnormal cervical cytology and had VIA followed by colposcopy with directed biopsy and endocervical curettage (ECC). If a cervical quadrant had no lesion, a random biopsy at the squamocolumnar junction within that quadrant was obtained. Sensitivity of colposcopic-directed biopsy was higher for >/=CIN 2 involving 3-4 cervical quadrants (81.3%) than for >/=CIN 2 involving 0-2 quadrants (49.0%, p < 0.001). Sensitivities of VIA, cytology of >/=ASC-US, >/=LSIL, and >/=HSIL were higher for >/=CIN 2 involving 3-4 quadrants than for >/=CIN 2 involving 0-2 quadrants. When a colposcopic-directed biopsy gold standard was compared with that of a 5-biopsy standard (which included >/=CIN 2 from colposcopic-directed biopsy, random biopsy, or ECC), the sensitivity for >/=CIN 2 of VIA was inflated by 20.0% (65.9% vs. 45.9%, p < 0.001). Sensitivities of other screening tests were not affected. Similar inflation of sensitivity of VIA was found with an endpoint of >/=CIN 3 (70.4% vs. 52.0%, p = 0.0013). Inflation of sensitivity of VIA depended upon agreement between colposcopic-directed biopsy and the screening tests as measured by kappa. Studies of VIA that used colposcopic-directed biopsy as the gold standard require reevaluation.     

Evaluation of Several Screening Approaches for Detection of Cervical Lesions in Rural Shandong,China

Purpose: The study was designed to: (1) investigate the prevalence of high-risk human papillomavirus (HRHPV)infection and cervical neoplasia; and (2) evaluate clinical performance of visual inspection with aceticacid/ Lugol’s iodine (VIA /VILI), Pap smear, high-risk human papillomavirus (HR-HPV) DNA test for detectingcervical intraepithelial neoplasia grade 2 or worse (CIN2+) and (3) explore appropriate screening approach inrural areas of Shandong Province. Materials and Methods: A total of 3,763 eligible women from Yiyuan Countyin Yimeng mountainous areas of rural Shandong, China, were enrolled and underwent Pap smear, HR-HPVDNA testing by Hybrid Capture 2 (HC2), and VIA /VILI tests. Women positive in any test were referred tocolposcopy and biopsy as indicated. Results: The prevalence of HR-HPV infection among all enrolled womenwas 11.1% and that in healthy women was 9.9%. In total 33 cases of CIN1, 16 cases of CIN2, 6 cases of CIN3 butnone of cervical cancer were detected and the crude prevalence of CIN2+ was 0.58%. For detecting CIN2+, thesensitivity of HR-HPV DNA testing, VIA/VILI, Pap smear was 90.9%, 77.3%, 81.8%, respectively. Pap smearhad the best specificity of 98.2%, followed by HR-HPV DNA testing with specificity of 89.4%, VIA/VILI hadthe lowest specificity of 81.2%. Colposcopy referral rate of HR-HPV DNA testing, VIA/VILI, Pap smear was11.1%, 18.5%, 2.3%, respectively. Conclusions: Our results suggest that HR-HPV DNA testing alone might beappropriate for primary cervical cancer screening in rural low-resource areas of Shandong Province, China.     

Evaluation of cytology and visual triage of human papillomavirus‐positive women in cervical cancer prevention in India

Although virtually all cervical cancers and most cervical intraepithelial neoplasia (CIN) are caused by persistent human papillomavirus (HPV) infection, only a small proportion of HPV‐positive women have or will develop CIN. Triaging HPV‐positive women has been suggested to reduce the false‐positive rate and proportion of women referred for CIN confirmation and/or treatment. In two cross‐sectional studies and one randomized trial in India, we evaluated the impact of using cytology or visual inspection with acetic acid (VIA) to triage HPV‐positive women on the proportion of women who would be referred for CIN confirmation and on the detection rates of high‐grade CIN. We present the numbers of HPV test‐positive women found and the CIN detected among them. We further assess the proportions that would be referred for CIN confirmation with colposcopy/biopsy and CIN that would be detected if cytology triage or VIA triage were used. Using cytology triage at atypical squamous cells of undetermined significance threshold or VIA triage reduced referrals for colposcopy by about 62% and 59%, respectively (p‐value = 0.012), but missed around 16% and 18%, respectively, of the high‐grade CIN (p‐value = 0.539) indicating similar performance of both triaging approaches. The choice of a triage test in different low‐ and middle‐income countries (LMIC) would depend on the availability and affordability in the particular setting. Cytology triage may be considered in settings where adequate infrastructure exists, whereas VIA triage may be suitable in settings with limited or no cytology infrastructure.     

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.     

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.     

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。     

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. ‍     

Accuracy of the Triple Test Versus Colposcopy for the Diagnosis of Premalignant and Malignant Cervical Lesions

Background: Despite the World Health Organization (WHO) recommendations concerning the use of alternative tests for the detection of cervical cancer precursor lesions in low-income countries, the accuracy of these tests is a debated issue. In the present study we compare the diagnostic accuracy of the triple test with that of colposcopy for the diagnosis of premalignant and malignant cervical lesions. Methods: A cross-sectional study was performed in 328 women referred to the gynecology clinic at Shahid Sadoughi Hospital, affiliated to Yazd University of Medical Sciences (SSUMS), Yazd, Iran, from March 2016 to June 2018. As the first step, a Pap smear was obtained from all participants. Visual inspection with acetic acid (VIA) and Lugol’s iodine (VILI) was performed in accordance with the known protocol. A colposcopy was then conducted in all participants, biopsy samples were obtained, and histological features studied. Finally, the results were compared by statistical analysis. Results: The age range of the participants was 30 - 50 years. Of 328 women, 60 (18.3 %) were postmenopausal. Two-hundred and five patients (62.5 %) had an abnormal Pap smear, 165 (50.3 %) had abnormal results on colposcopy, and 141 (43 %) had abnormal histopathology reports. The VIA was positive in 129 patients (39.3 %) and the VILI in 177 (54 %). The results of the triple test were reported to be positive in 205 cases (51.52 %). The sensitivity of the triple test in the detection of premalignant and malignant cervical lesions was 78.7 % and 69 %, respectively. The sensitivity and specificity of colposcopy in the detection of premalignant and malignant cervical lesions was 80.1 % and 72.2 %, respectively. The diagnostic accuracy of the triple test and colposcopy in the detection of premalignant and malignant cervical lesions was 73 % versus 75 %. Conclusion: Since the results of the study showed that the diagnostic accuracy of the triple test is equivalent that of colposcopy, the former may be used in low-income countries and areas lacking access to colposcopy.     

Accuracy of visual inspection with acetic acid to detect cervical cancer precursors among HIV‐infected women in Kenya

Visual inspection with acetic acid (VIA) is becoming a more widely recommended and implemented screening tool for cervical cancer prevention programs in low‐resource settings. Many of these settings have a high prevalence of HIV‐infected women. We carried out a cross‐sectional validation study to define the sensitivity, specificity and predictive values of VIA among HIV‐infected women. Women enrolled in HIV care at the Family AIDS Care and Education Services clinic in Kisumu, Kenya, were recruited for participation. All participants underwent VIA followed by colposcopy performed by a second blinded clinician. At colposcopy, lesions suspicious for cervical intraepithelial neoplasia 2 or greater (CIN2+) were biopsied. Disease status was determined by final histopathologic diagnosis in women who underwent biopsies. A satisfactory colposcopy with no lesions was considered a negative result. From October 2010 to June 2012, 1,432 women underwent VIA and colposcopy. A total of 514 (35.7%) women had a positive VIA, and 179 (12.2%) had CIN2+ confirmed by colposcopically directed biopsy. Sensitivity, specificity, positive and negative predictive values of VIA for CIN2+ were 86.6, 71.6, 30.3 and 97.4%, respectively. Specificity, but not sensitivity, increased with older age. Among older women, sensitivity was affected by CD4+ count and use of antiretroviral therapy. Although they are impacted by age and immune status, test characteristics for VIA among HIV‐infected women are similar to what has been reported for general populations. Recommendations to use VIA as a screening tool should not vary by HIV status.     

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.     

Performance of a low cost magnifying device,magnivisualizer, versus colposcope for detection of pre-cancer and cancerous lesions of uterine cervix

Objective

To assess the performance of a low cost magnifying device (Magnivisualizer) compared to a standard optical colposcope for detection of precancerous and cancerous lesions of the uterine cervix.

Methods

A total of 659 consecutive symptomatic women attending a gynecologic outpatient clinic underwent unaided visual inspection followed by cytology, visual inspection of the cervix using 5% acetic acid (VIA), and VIA under magnification (VIAM) with the Magnivisualizer. All women, independently of test results, were referred for colposcopic examination. Colposcopic-directed biopsies were obtained from all positive lesions and compared to positive VIAM cases.

Results

The detection rate for VIA positive lesions was 12% (134/659), while it was 29% for VIAM positive lesions (191/659). The sensitivities of detection of cervical intraepithelial neoplasia (CIN) 2 and higher lesions were 61.7% for VIA, 88.3% for VIAM, and 86.7% for colposcopy, with a specificity of 58.5% for VIA, 55.8% for VIAM, and 90.4% for colposcopy. The performance of colposcopy and VIAM was moderate (κ, 0.48; 95% confidence interval [CI], 0.41 to 0.54) for detection of CIN 1 and higher lesions and excellent (κ, 0.87; 95% CI, 0.82 to 0.94) for detection of CIN 2 and higher lesions.

Conclusion

In low resource settings, where colposcopic facilities are not available at the community level, a simple low-cost, handheld Magnivisualizer can be considered a valid option for detection of cervical precancerous and cancerous lesions. However, it cannot replace traditional colposcopy because it has a low specificity that results in many unnecessary biopsies.     

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.     

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。