Performance of point-of-care testing for cervical cancer screening / 中华预防医学杂志

Objective: To evaluate the performance of point-of-care testing for cervical cancer and precancerous lesions screening. Methods: In September 2020, 197 and 273 women were selected by using simple random sampling method from "self-sampling" cohort and "physician-sampling" cohort established in Xiangyuan county, Shanxi Province, China, respectively. Cervical exfoliated cells were collected by women themselves or gynecologists. All samples were detected by POCT and women with positive result were directly referred for colposcopy. Subsequently, all the samples were detected by careHPV and PCR test. Colposcopy and punch biopsy were performed for women with POCT negative but careHPV or PCR test positive at another visit. Using histopathological diagnosis as the gold standard, we calculated sensitivity, specificity and drew the receiver operating characteristic (ROC) curves. The accuracy of POCT was analyzed and compared to that of careHPV and conventional PCR test in cervical cancer and precancerous lesions screening. Results: The median (Q1 , Q3) age of 470 women was 51 (45, 57) years old. Based on self-sampling, the sensitivity and specificity of POCT for CIN2+ were 100.00% (95%CI: 56.56%-100.00%) and 28.95% (95%CI: 22.97%-35.76%), respectively. Compared with POCT, POCT HPV16/18 test had similar sensitivity and higher specificity of 89.47% (95%CI: 84.30%-93.08%). Self-sampling POCT HPV16/18 test had an AUC of 0.947 (95%CI:0.910-0.985), which was higher than that of careHPV and PCR test. Physician-sampling POCT test had 100.00% sensitivity (95%CI: 64.57%-100.00%) and 55.85% specificity (95%CI: 49.83%-61.70%) for detecting CIN2+. POCT HPV16/18 test had lower sensitivity (71.43%, 95%CI: 35.90%-91.76%) and higher specificity (92.45%, 95%CI: 88.63%-95.06%). POCT HPV16/18 test generally showed similar AUC on both self-collected samples and clinician-collected samples (0.947 vs 0.819, P=0.217). Conclusion: POCT HPV16/18 test is an effective method with relatively high sensitivity and specificity for cervical cancer screening.

Effectiveness and health economic analysis of strategies on cervical cancer screening and early diagnosis and treatment / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the appropriate strategies which are suitable for the areas with diverse health and economic resource settings in China by estimating the life outcomes and cost-effectiveness of several cervical cancer screening strategies.</p><p><b>METHODS</b>Markov model was used to calculate the long-term effectiveness, utility, benefit and cost among screened and unscreened cohorts in rural and urban areas, and then analyses of cost-effectiveness, cost-utility and cost-benefit were performed. The assessed screening strategies were acetic acid of visual inspection combined with Lugol's iodine staining (VIA/VILI), conventional Pap smear and simple HPV DNA testing (careHPV) in rural areas, and conventional Pap smear, simple HPV DNA testing (careHPV), HPV DNA testing (HC2) and liquid-based cytology (LBC) alone or combined with HPV DNA testing (LBC+HC2) in urban areas. We estimated the life outcomes and cost-effectiveness of the above screening strategies at one-year, 3-year and 5-year intervals.</p><p><b>RESULTS</b>All of the screening strategies were effective to decrease cervical cancer mortality and to increase life years, with a trend of shorter screening interval having better effectiveness. However, no matter in urban or rural areas, compared with careHPV testing at 5-year interval, the costs of other screening strategies were 1.28 - 13.86 folds, 1.31 - 14.14 folds, and 1.27 - 12.80 folds higher to avoid one death, to save a year of life, and a QALY, and the benefit per cost of other screening strategies was 9.9%-90.2%.</p><p><b>CONCLUSIONS</b>careHPV testing at 5-year interval has the best cost-effectiveness performance and the highest benefit-cost ratio with the moderate life outcomes. It is the optimal cervical cancer screening strategy to be generalized in our country. careHPV testing at 3 years interval can be considered in more developed areas to achieve better effectiveness.</p>

Three-year follow-up results of visual inspection with acetic acid/Lugol's iodine (VIA/VILI) used as an alternative screening method for cervical cancer in rural areas / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>In China, there has been no established national program for cervical cancer prevention, the screening methods and experiences are especially deficient in the rural areas. The aim of this paper is to evaluate the effects of acetic acid/Lugol's iodine (VIA/VILI) used for screening of cervical cancer and pre-cancerous lesions in a rural area of China by analyzing the large-scale population-based screening data from the demonstration site.</p><p><b>METHODS</b>Women aged 30-59 years from Xiangyuan County in Shanxi Province were recruited for cervical cancer screening from 2005 to 2007. VIA/VILI was the primary screening method followed by colposcopy if the VIA/VILI was positive. Cervical lesions were diagnosed by directed biopsy under the colposcopy. The VIA/VILI negative women or cervical intraepithelial neoplasia 1 (CIN1) were re-screened using the same procedure in the next year.</p><p><b>RESULTS</b>In total, 7145 women received the cervical cancer screening, with a participation rate of 74.75%. Their average age was 42.16 years. A total of 1287 women were consecutively screened for three times from 2005 to 2007. The detection rates of CIN2, CIN3 and cervical cancer were 0.70% (9/1287), 1.01% (13/1287) and 0.23% (3/1287) for the first round screening, and were 0.22% (2/976), 0.11% (1/976) and 0% (0/976) for the second round screening, respectively. Only one CIN2 was found in the third round screening. In the years of 2006-2007, 3490 women were screened consecutively twice. The detection rates of CIN2, CIN3 and cervical cancer were 0.26% (9/3490), 0.52% (18/3490) and 0.15% (5/3490) for the first round screening, and 0.40% (14/2943), 0.40% (14/2943) and 0.03% (1/2943) for the second round screening. Likewise, 2 368 women were screened consecutively twice in the years of 2007-2008. The detection rates of CIN2, CIN3 and cervical cancer were 0.55% (13/2368), 0.25% (6/2368) and 0.12% (3/2368) for the first round screening, and 0.42 (10/2040), 0.04% (1/2040) and 0% for the second round screening. The cumulative detection rates for CIN2, CIN3 and cervical cancer were 0.81% (58/7145), 0.74% (53/7145) and 0.17% (12/7145), respectively. And 53.45% (31/58) of CIN2, 68.81% (37/53) of CIN3 and almost all cervical cancers (11/12) were found during the first round screening, except for an early stage cervical cancer (Ia). Only one CIN2 was detected in the third round screening in the same population. The average age of CIN1, CIN2, CIN3 and cervical cancer were 38.65, 40.61, 44.10 and 46.73 years, respectively.</p><p><b>CONCLUSIONS</b>VIA/VILI can be used as an alternative screening method for cervical cancer and high-grade pre-cancerous lesions among the women aged 30-59 years in China's rural areas because of its low cost, easy training for the local health providers, and less depending on facilities. One round screening by VIA/VILI can detect more than a half of CIN2, two-thirds of CIN3 and almost all the cervical cancer in the population, and the detection rates of CIN2/3 can be increased by two consecutive rounds of screening.</p>

A study of cervical cancer screening algorithms / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To assess the feasibility and accuracy of different cervical cancer screening algorithms suitable for different regions, and promote the prevention and control of cervical cancer in China.</p><p><b>METHODS</b>Using the data of a cross-sectional comparative trial of multiple techniques to detect cervical intraepithelial neoplasia in Xiangyuan County, Shanxi Province, conducted in 1999, to evaluate the feasibility and accuracy of different cervical cancer screening algorithms. All the women were screened by six screening tests, including liquid based cytology (LBC), fluorescence spectroscopy, visual inspection with 5% acetic acid staining (VIA), colposcopy, self-sampled HPV DNA and clinician-sampled HPV DNA test, and each woman had histopathological diagnosis. Different screening algorithms were developed by combining the screening tests in parallel or in serial, and the performance indexes of the algorithms such as sensitivity, specificity, colposcopy referral rate and receiver operating characteristic (ROC) curve for detecting the high grade lesions (>or= CIN 2) were compared.</p><p><b>RESULTS</b>Among the algorithms combined by LBC and HPV DNA testing, for the combination in parallel (either cytology was greater than ASC-US or HPV positives), its sensitivity was 100%, specificity was 68.6%, and colposcopy referral rate was 34.4%; for the algorithm of LBC as primary screening test, with ASC-US women triage by HPV DNA testing, its sensitivity was 93.0%, specificity was 89.9%, and colposcopy referral rate was 13.7%; for the algorithm of HPV DNA testing as the primary screening test, with HPV positive women triage by LBC, its sensitivity was 91.7%, specificity was 93.0%, and colposcopy referral rate was 10.6%. ROC analysis showed that LBC primary testing followed by HPV triage and HPV primary testing followed by LBC triage were much better than the combination in parallel (P = 0.0003, P = 0.0002). Among the algorithms with LBC or HPV DNA testing solely as primary screening test, the sensitivity, specificity and colposcopy referral rate of LBC were 94.2%, 77.3%, 25.7% and 87.2%, 93.5%, 10.0%, respectively, for cutoff by ASC-US or by LSIL; the sensitivity, specificity and colposcopy referral rate of HPV DNA testing were 97.6%, 84.8%, 18.8% and 83.5%, 85.9%, 17.1%, respectively, for clinician-sampled and self-sampled. Clinician-sampled HPV DNA testing was better than LBC cutoff by ASC-US or self-sampled HPV DNA testing (P = 0.005, P = 0.002). Among the algorithms combined by VIA and HPV DNA testing, the sensitivity, specificity and colposcopy referral rate were 70.9%, 74.3% and 27.6% for VIA alone as primary screening test; the sensitivity, specificity and colposcopy referral rate were 65.9%, 95.2% and 7.4% for HPV as primary screening test with HPV positive women triage by VIA. HPV primary testing followed by VIA triage was better than VIA alone (P = 0.004).</p><p><b>CONCLUSION</b>Considering the health-resource settings and women's preference, both HPV primary testing followed by LBC triage and LBC primary testing followed by HPV triage are suitable for developed regions, moderately developed regions may choose either LBC or HPV as the screening approach, VIA is a suitable primary screening test in less developed regions, and HPV primary testing followed by VIA triage will be more effective if low cost HPV test is available in the future.</p>

Feasibility of packaging screening for cervical cancer, breast cancer, and reproductive tract infection in a rural area in China / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the prevalence of cervical cancer, breast cancer, and reproductive tract infection (RTI) among women living in a county of China, identify these women's recognition about these three diseases and their attitude toward the screening, and evaluate the feasibility of the packaging screening program in rural areas in China.</p><p><b>METHODS</b>In this cross-sectional study, women aged 30-59 living in Xiangyuan County, Shanxi Province, were surveyed by questionnaires and screened with visual inspection of cervix, breast clinic examination, and combined clinical examination and laboratory tests for RTI.</p><p><b>RESULTS</b>Totally 630 women underwent interviews and packaging screening. The prevalences of cervical precancerous lesion, breast benign disease, and RTI were 0.2%, 14.0%, and 53.2%, respectively. No cancer case was found. The percentages of women knowing cervical cancer, breast cancer, and RTI as common diseases in women were 70.5%, 63.5%, and 52.9% after health education. Up to 92.5% of women preferred packaging screening to screening for single disease; however, they were not willing to pay the screening at current high cost.</p><p><b>CONCLUSIONS</b>The prevalences of breast benign disease and RTI are relatively high among women in rural areas in China. The women's recognition about these three diseases is moderately good. The packaging screening program is well accepted and feasible in rural areas.</p>

Association between high-risk human papillomavirus DNA load and cervical intraepithelial lesion / 中华流行病学杂志

<p><b>OBJECTIVE</b>To determine the association between viral load of high risk type human papillomavirus (HR-HPV) and stage of cervical intraepithelial neoplasia (CIN) lesion.</p><p><b>METHODS</b>Cervical exfoliated cells were collected from 1997 women aged 35-45 in a cross-sectional screening study. HPV DNA was detected by hybrid capture 2 (HC2) system, and viral load was measured by the ratios of relative light units compared to standard positive control (RLU/PC). Log10RLU/PC were categorized into four groups: negative (< 0), low viral load (0 - 1.12), medium viral load (1.13 - 2.23), and high viral load (2.24 - 3.37). Cervical lesions were diagnosed by biopsies as normal, CIN 1, CIN 2-3, and squamous cervical cancer (SCC). Association between HR-HPV and CINs were evaluated by unconditional multinomial logistic regression.</p><p><b>RESULTS</b>100% (12/12) SCC, 97.3% (72/74) of CIN 2-3, 58.3% (74/127) of CIN 1, and 11.5% (205/1784) of normal women were positive for HPV DNA. The median log10RLUs for the positive women with SCC, CIN 2-3, CIN 1 and in normal women were 2.60, 2.32, 2.18 and 1.18 respectively. The odds ratio (OR) between low viral load of HPV DNA and CIN 1 was 3.8 (1.9 - 7.3) while between high viral load and CIN 2-3 was OR=865.9 (200.1 - 3738.0) which showed that higher viral load could increase the risk of cervical lesions (P <0.001).</p><p><b>CONCLUSION</b>Both cervical cancer and CINs were highly influenced by HR-HPV viral load.</p>