VIA、VILI在农村宫颈癌筛查中的应用

目的 寻找适合农村地区子宫颈癌及其癌前病变的筛查方法,为降低子宫颈癌的发病率及病死率提供科学方法.方法 以湖北省五峰县（宫颈癌早诊早治项目县之一）长乐坪镇30-59岁的已婚妇女作为对象,进行以人群为基础的子宫颈癌筛查,对符合条件的妇女进行危险因素、癌症及子宫颈癌认知情况的问卷调查,5%醋酸染色后肉眼观察（VIA）和2%的卢戈氏碘染色后肉眼观察（VILI）结果异常者,进行阴道镜下活组织检查并得到最终的病理学诊断,将病变检出率与同年在五峰县其它乡镇的宫颈刮片细胞学筛查结果进行比较.结果 该次筛查人群参与率为70%,最终经活检病理确诊的CINⅠ患病率为0.5%（10例）,CINⅡ0.5%（11例）,CINⅢ1.0%（20例）,子宫颈癌0.1%（2例）;宫颈癌及其癌前病变有年轻化趋势;该次单纯由肉眼观察对CINⅠ、CINⅡ的病变检出率,与同年在当地其它乡镇宫颈刮片细胞学普查结果相当,差别无统计意义,但对≥CINⅢ的病变检出率高于宫颈刮片细胞学筛查结果,有统计学意义.结论 肉眼观察是一种经济有效的宫颈癌筛查方法,适宜在农村地区推广,能使更多贫困地区的妇女及时得到子宫颈癌的早诊早治.     

山西省农村妇女宫颈癌筛查结果分析

[目的]评价2014年山西省农村妇女宫颈癌检查结果,探讨宫颈癌流行趋势与特点,为进一步推进宫颈癌筛查工作提供科学依据.[方法]回顾性分析2014年宫颈癌筛查项目35～64岁农村已婚妇女的筛查数据资料.[结果]2014年共计完成408 618例农村妇女的免费宫颈癌筛查,检出宫颈癌前病变721人,检出率为176.44/10万;检出宫颈癌215人,检出率为52.62/10万.[结论]进行育龄妇女人群的健康教育,加强高危人群管理,重点培训参加宫颈癌筛查的基层医师,是提高宫颈癌早诊早治的关键.     

HPV检测在农村宫颈癌筛查中的作用

[目的]了解HPV检测在辽宁省沈阳市苏家屯地区农村妇女宫颈癌筛查过程中的作用,为宫颈癌筛查提供科学依据.[方法]对2014～2015年间自愿接受宫颈癌筛查的35～64岁农村常住妇女,进行调查、取样和HPV检测.[结果]对10 000名35～64岁妇女进行宫颈癌筛查,发现宫颈癌癌前病变80人(其中CIN1为36人,CIN2为30人,CIN3为14人),宫颈癌3人.高危型HPV阳性共1209人,高危型HPV阳性感染率随年龄的升高而升高.HPV的感染率随着病变程度加重而升高;宫颈上皮内瘤变和宫颈癌组HPV 16型的比例显著性高于其他组.[结论] HPV检测在宫颈癌的筛查过程中对提高早诊率具有重要的意义.     

肉眼观察(VIA、VILI)在中国农村地区宫颈癌筛查中的应用评价

目的评价醋酸、碘着色肉眼观察在中国农村地区宫颈癌筛查中的应用价值及可行性。方法对子宫颈癌高发区江西省修水县大桥乡妇女进行以人群为基础的研究,对2499例年龄为30～49岁农村已婚妇女进行了人乳头瘤病毒(HPV)的检测,薄层液基细胞学(TCT),醋酸、碘染色后肉眼观察(VIA、VILI)以及电子阴道镜检查。各种方法独立进行,均为双盲。对VIA、VILI或电子阴道镜中任何一项存在阳性病变进行宫颈组织活检,或行颈管刮术(ECC),另HPV或TCT阳性的妇女也给予活检。宫颈组织病理诊断均经国际癌症研究所病理检查确诊,将CIN2以上(含CIN2)病变纳入阳性结果。结果2499例受检妇女中有2432例列入研究,共检出CIN237例,CIN359例,宫颈癌3例。HPV,TCT,HPV TCT,VIA,VILI,VIA VILI和阴道镜检查等筛查方法的敏感度分别是96.67%,89.47%,97.98%,56.57%,36.36%,63.64%和39.39%;特异度分别为85.00%,96.91%,86.97%,94.60%,96.23%,92.97%和98.14%。结论VIA、VILI的灵敏度低于HPV或TCT,但因其简单、廉价、易掌握等特点,故更适合在农村地区推广应用。     

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.     

醋酸染色肉眼观察法筛查宫颈病变的效果及其误判的影响因素

[目的]分析醋酸染色肉眼观察(VIA)筛查宫颈病变的效果,并初步探讨其误判的影响因素。[方法]将3179名进行HPV检测、VIA检查的联合筛查妇女纳入分析,任意一种筛查方法阳性妇女和10%随机抽取的所有筛查试验阴性的1112名妇女进行阴道镜检查,阴道镜下可见病变处直接取活检,不可见病变且筛查阳性时四象限随机活检+宫颈管搔刮术(ECC),以病理诊断为金标准。[结果 ]在3179名纳入分析的筛查对象中,HPV感染率为24.6%(782/3179),VIA阳性率为6.2%(197/3179)。VIA检出宫颈高度以上病变(CIN2+)病变的灵敏度仅为31.5%,特异性为94.2%,漏诊率为68.5%,误诊率为5.8%。多因素分析结果显示,绝经妇女行VIA检查更容易被漏诊;而年龄小、鳞柱交界满意和有宫颈炎的妇女行VIA检查更容易被误诊。[结论]影响VIA检查准确性的因素较多,临床判断的主观性较大,需要对临床医生开展标准化培训,对于绝经和有生殖道炎症的妇女行VIA检查时更需慎重。     

妊娠期宫颈上皮内瘤样病变的筛查及治疗

综述了妊娠期宫颈上皮内瘤样病变的筛查方法，强调保守性治疗，反复阴道镜检查及镜下活检是安全可靠的，追加醋酸白试验可增加过度诊断，但敏感性可大大提高，如果阴道镜检查排除宫颈浸润癌，妇产科医生可将治疗时间推迟至产后，母婴危险性将降低。LEEP（loop electrosurgical excision)治疗及宫颈锥切只应有于病理或阴道镜检查高度可疑癌或已证实为部症的孕妇，妊娠期CIN转归率较高，但必须严密随访。     

阴道镜筛查CIN及早期宫颈癌78例分析

目的进一步评价阴道镜在宫颈上皮内瘤病变(CIN)及宫颈癌早期诊断中的价值。方法回顾性分析450例,进行阴道镜检查,行镜下定位取活组织病理检查,并与宫颈细胞涂片结果进行对比。结果450例中检出宫颈CINⅠ15例,CINⅡ19例,CINⅢ11例,宫颈鳞癌33例和宫颈湿疣15例,其余357例为慢性宫颈炎。宫颈CCT细胞涂片检出了71.8%宫颈病变,阴道镜检出了80.8%宫颈病变,细胞学与阴道镜下活检联合应用无漏诊。结论阴道镜检查是诊断CIN和宫颈癌的一个可靠方法,细胞学与阴道镜下活检联合应用能提高宫颈病变的检出率。     

2020-2022年湖南省326824名宫颈癌筛查和健康体检者HPV感染率及亚型分布

目的 分析湖南省女性人乳头瘤病毒(HPV)感染情况以及HPV亚型与宫颈上皮细胞和组织病理改变的关系,为当地HPV流行病学提供数据支持。方法 采集2020-2022年湖南省326 824名参加宫颈癌筛查和健康体检人群的宫颈脱落上皮细胞,采用荧光PCR技术检测其HPV分型,统计分析不同年龄、地区各HPV分型感染状况;其中9 940例进行液基薄层细胞学检查(TCT)检查或病理学检查,分析其HPV感染情况与细胞病理学阳性结局的关系。结果 HPV总体感染率为10.9%(35 646/326 824),其中单一型感染占81.9%(29 201/35 646),多重型感染占18.1%(6 445/35 646);单一型占比前6位型别依次为HPV52(20.5%)、HPV58(16.0%)、HPV16(12.9%)、HPV53(11.9%)、HPV81(8.7%)和HPV70(8.6%)。≥60岁组感染率最高,为15.7%(3 672/23 315),HPV感染阳性人群中,不同年龄组多重型感染占比总体差异有统计学意义,χ²=365.910,P<0.001。按病例来源划分,感...     

农村地区醋酸/碘染色法筛查子宫颈癌的3年结果分析

背景与目的:我国至今还没有一个系统的子宫颈癌防治计划,尤其是广大农村地区更缺乏子宫颈癌的防治技术和经验。本研究报道山西省襄垣县子宫颈癌早诊早治示范基地的人群筛查资料,评价基层医生采用醋酸或碘染色法(VIA/VILI)在农村地区筛查子宫颈癌及其癌前病变的效果。方法:采用醋酸染色法(VIA)和碘染色法(VILI)在山西省襄垣县30～59岁的妇女人群中开展子宫颈癌筛查,VIA或VILI阳性者进行阴道镜检查,阴道镜检异常者在病变处取活检进行病理学诊断。采用同样的程序对人群进行复查,通过比较1年筛查、连续2年筛查和连续3年筛查的结果,评价该方案的筛查效果。结果:在2005～2008年期间,有7145名适龄妇女参加了筛查,平均年龄为42.16岁,筛查人群平均参与率为74.75%。其中2005～2007年期间,对1287人连续筛查了3年,第1轮筛查CIN2、CIN3及子宫颈癌的检出率分别为0.70%(9例)、1.01%(13例)、0.23%(3例);第2轮(976人)筛查检出率分别为0.22%(2例)、0.11%(1例)、0;第3轮筛查仅增加了1例CIN2病例。2006～2007年期间对3490人连续筛查了2年,第1轮(3...     

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.     

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.     

Accuracy of visual screening for cervical neoplasia: Results from an IARC multicentre study in India and Africa

Visual inspection-based screening tests, such as visual inspection with 4% acetic acid (VIA) and with Lugol's iodine (VILI), have been proposed as alternatives to cytology in mass screening programs. To date, there is only limited information on the accuracy of these tests in detecting High-grade Squamous Intraepithelial Lesions (HSIL). Eleven cross-sectional studies involving 56,939 women aged 25-65 years were conducted in Burkina Faso, Congo, Guinea, India, Mali and Niger to evaluate the accuracy of VIA and VILI performed by health workers. A common protocol and questionnaire was used. For final diagnosis, all women were investigated with colposcopy and biopsies were taken when necessary. Data from the studies were pooled to calculate sensitivity, specificity and predictive values of the tests for the detection of HSIL. Of the screened women, 16.1% and 16.4% were positive on examination using, respectively, VIA and VILI; 1,063 were diagnosed with HSIL. The pooled sensitivity, specificity, positive and negative predictive values for VIA were 76.8% (95% CI: 74.2-79.4%), 85.5% (95% CI: 85.2-85.8%), 9.4% (95% CI:8.8-10.8%) and 99.5% (95% CI:99.4-99.6%), respectively. The values were 91.7% (95% CI: 89.7-93.4%), 85.4% (95% CI: 85.1-85.7%), 10.9% (95% CI: 10.2-11.6%) and 99.8% (95% CI:99.7-99.9%), respectively for VILI. The range of sensitivity and specificity for VIA was 56.1-93.9% and 74.2-93.8%, respectively, between studies and were 76.0-97.0 % and 73.0-91.3% for VILI. VILI had a significantly higher sensitivity than VIA in detecting HSIL, but specificity was similar. VILI appears to be a more accurate visual test for use in screening and treatment programs in low-resource settings.     

Single-visit approach of cervical cancer screening: See and Treat in Indonesia

Background:

We performed a cross-sectional study in Indonesia to evaluate the performance of a single-visit approach of cervical cancer screening, using visual inspection with acetic acid (VIA), histology and cryotherapy in low-resource settings.

Methods:

Women having limited access to health-care facilities were screened by trained doctors using VIA. If the test was positive, biopsies were taken and when eligible, women were directly treated with cryotherapy. Follow-up was performed with VIA and cytology after 6 months. When cervical cancer was suspected or diagnosed, women were referred. The positivity rate, positive predictive value (PPV) and approximate specificity of the VIA test were calculated. The detection rate for cervical lesions was given.

Results:

Screening results were completed in 22 040 women, of whom 92.7% had never been screened. Visual inspection with acetic acid was positive in 4.4%. The PPV of VIA to detect CIN I or greater and CIN II or greater was 58.7% and 29.7%, respectively. The approximate specificity was 98.1%, and the detection rate for CIN I or greater was 2.6%.

Conclusion:

The single-visit approach cervical cancer screening performed well, showing See and Treat is a promising way to reduce cervical cancer in Indonesia.     

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.     

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.     

Initial results from a randomized trial of cervical visual screening in rural south India

The impact of a single round of screening of visual inspection with acetic acid (VIA) on cervical cancer incidence and mortality was investigated in a cluster randomized trial in south India. Women 30-59 years of age in 113 clusters in Dindigul District were randomized to VIA screening (57 clusters, 48,225 women) by nurses and to a control group (56 clusters, 30,167 women). 30,577 eligible women were screened between May 2000 and April 2003; 2,939 (9.6%) screen-positive women were investigated with colposcopy by nurses and 2,777 (9.1%) women had biopsy. CIN 1 was diagnosed in 1,778 women, CIN 2-3 lesions were found in 222, and there were 69 screen detected invasive cervical cancers. The detection rates of lesions per 1,000 screened women were 58.2 for CIN 1, 7.3 for CIN 2-3, and 2.3 for invasive cancer. The detection rate of high-grade lesions in our study was 2-3-fold higher than those observed in repeatedly screened populations in developed countries. 71% of women with CIN 1 and 80% of those with CIN 2-3 lesions accepted cryotherapy provided by nurses and surgical treatment by mid-level clinicians. Overall, 97 and 34 incident cervical cancer cases were observed in the intervention and control arms, respectively. The intervention arm accrued 124,144 person years and the control arm accrued 90,172 during the study period. The age standardized cervical cancer incidence rates were 92.4/100,000 person-years in the intervention and 43.1/100,000 in the control arms. In the screened arm, 35.0% of cases were in Stage I as opposed to none in the control arm. The preliminary findings from our study indicate that not only is a VIA-based screening programme feasible, safe and acceptable to a population in rural settings, it also results in early detection of cervical neoplasia.     

Disease detection at the 48-month exit round of the HPV FOCAL cervical cancer screening trial in women per-protocol eligible for routine screening

HPV FOCAL is a randomized control trial of cervical cancer screening. The intervention arm received baseline screening for high-risk human papillomavirus (HPV) and the control arm received liquid-based cytology (LBC) at baseline and 24 months. Both arms received 48-month exit HPV and LBC cotesting. Exit results are presented for per-protocol eligible (PPE) screened women. Participants were PPE at exit if they had completed all screening and recommended follow-up and had not been diagnosed with cervical intraepithelial neoplasia Grade 2 or worse (CIN2+) earlier in the trial. Subgroups were identified based upon results at earlier trial screening. There were 9,457 and 9,552 and women aged 25–65 randomized to control and intervention and 7,448 (77.8%) and 8,281 (86.7%), respectively, were PPE and screened. Exit cotest results were similar (p = 0.11) by arm for PPE and the relative rate (RR) of CIN2+ for intervention vs. control was RR = 0.83 (95% CI: 0.56–1.23). The RR for CIN2+ comparing intervention women baseline HPV negative to control women with negative cytology at baseline and at 24 months, was 0.68 (95% CI: 0.43–1.06). PPE women who had a negative or CIN1 colposcopy in earlier rounds had elevated rates (per 1,000) of CIN2+ at exit, control 31 (95% CI: 14–65) and intervention 43 (95% CI: 25–73). Among PPE women HPV negative at exit LBC cotesting identified little CIN2+, Rate = 0.3 (95% CI: 0.1–0.7). This per-protocol analysis found that screening with HPV using a 4-year interval is as safe as LBC with a 2-year screening interval. LBC screening in HPV negative women at exit identified few additional lesions.     

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.