Comparison of cervical cancer screening models based on Pap and HPV tests in Tbilisi, Georgia.

Cost-effectiveness of using human papillomavirus 16/18 genotype triage in cervical cancer screening

Primary cervical screening uses cytology to detect cancer precursor lesions [cervical intraepithelial neoplasia stage 3 or beyond (CIN3+)]. Human papillomavirus (HPV) testing could add sensitivity as an adjunct to cytology or as a first test, reserving cytology for HPV-positive women. This study addresses the questions: Does the combination of cytology and HPV testing achieve a reduction in incident CIN3+?; Is HPV testing cost-effective in primary cervical screening?; Is its use associated with adverse psychosocial or psychosexual effects?; and How would it perform as an initial screening test followed by cytology for HPV positivity? ARTISTIC was a randomised trial of cervical cytology versus cervical cytology plus HPV testing, evaluated over two screening rounds, 3 years apart. Round 1 would detect prevalent disease and round 2 a combination of incident and undetected disease from round 1. Women undergoing routine cervical screening in the NHS programme in Greater Manchester. In total 24,510 women aged 20-64 years were enrolled between July 2001 and September 2003. HPV testing was performed on the liquid-based cytology (LBC) sample obtained at screening. Women were randomised in a ratio of 3:1 to have the HPV test result revealed and acted upon if persistently positive in cytology-negative cases or concealed. A detailed health economic evaluation and a psychosocial and psychosexual assessment were also performed. The primary outcome was CIN3+ in round 2. Secondary outcomes included an economic assessment and psychosocial effects. A large HPV genotyping study was also conducted. In round 1 there were 313 CIN3+ lesions, representing a prevalence in the revealed and concealed arms of 1.27% and 1.31% respectively (p = 0.81). Round 2 (30-48 months) involved 14,230 (58.1%) of the women screened in round 1 and only 31 CIN3+ were detected; the CIN3 rate was not significantly different between the revealed and concealed arms. A less restrictive definition of round 2 (26-54 months) increased CIN3+ to 45 and CIN3+ incidence in the arms was significantly different (p = 0.05). There was no difference in CIN3+ between the arms when rounds 1 and 2 were combined. Prevalence of high-risk HPV types was age-dependent. Overall prevalence of HPV16/18 increased with severity of dyskaryosis. Mean costs per woman in round 1 were 72 pounds and 56 pounds for the revealed and concealed arms (p < 0.001); an age-adjustment reduced these mean costs to 65 pounds and 52 pounds. Incremental cost-effectiveness ratio for detecting additional CIN3+ by adding HPV testing to LBC screening in round 1 was 38,771 pounds. Age-adjusted mean cost for LBC primary screening with HPV triage was 39 pounds compared with 48 pounds for HPV primary screening with LBC triage. HPV testing did not appear to cause significant psychosocial distress. Routine HPV testing did not add significantly to the effectiveness of LBC in this study. No significant adverse psychosocial effects were detected. It would not be cost-effective to screen with cytology and HPV combined but HPV testing, as either triage or initial test triaged by cytology, would be cheaper than cytology without HPV testing. LBC would not benefit from combination with HPV; it is highly effective as primary screening but HPV testing has twin advantages of high negative predictive value and automated platforms enabling high throughput. HPV primary screening would require major contraction and reconfiguration of laboratory services. Follow-up continues in ARTISTIC while maintaining concealment for a further 3-year round of screening, which will help in screening protocol development for the post-vaccination era.

We aimed to evaluate the effectiveness of different triage strategies for high-risk human papillomavirus (hrHPV)-positive women in primary healthcare settings in China. This study was undertaken in 11 rural and 9 urban sites. Women aged 35-64 years old were enrolled. HrHPV-positive women were randomly allocated to liquid-based cytology (LBC), visual inspection with acetic acid and Lugol's iodine (VIA/VILI) (rural only) triage, or directly referred to colposcopy (direct COLP). At 24 months, hrHPV testing, LBC and VIA/VILI were conducted for combined screening. In rural sites, 1,949 hrHPV-positive women were analyzed. A total of 852, 218 and 480 women were randomly assigned to direct COLP, LBC and VIA/VILI. At baseline, colposcopy referral rates of LBC or VIA/VILI triage could be reduced by 70%-80%. LBC (n=3 and n=7) or VIA/VILI (n=8 and n=26) could significantly decrease the number of colposcopies needed to detect one cervical intraepithelial neoplasia (CIN) 2 or worse and CIN3+ compared with direct COLP (n=14 and n=23). For the 24-month cumulative detection rate of CIN2+, VIA/VILI triage was 0.50-fold compared with LBC triage and 0.46-fold with the direct COLP. When stratified by age, baseline LBC triage+ performed best (P<0.001), peaking among women aged 35-44 years (Ptrend=0.002). In urban sites, 1,728 women were hrHPV genotyping test positive. A total of 408, 571 and 568 women were randomly assigned to direct COLP for HPV16/18+, direct COLP for other hrHPV subtypes+, and LBC triage for other hrHPV subtypes+. LBC (n=12 and n=31) significantly decreased the number of colposcopies needed to detect one CIN2+ and CIN3+ compared with direct COLP (n=14 and n=44). HPV16/18+ increased the 24-month cumulative detection rate of CIN2+ (17.89%, P<0.001). LBC triage for hrHPV-positive women in rural settings and direct COLP for HPV16/18+ women and LBC triage for other hrHPV subtype+ women in urban settings might be feasible strategies.

ObjectiveCervical cancer screening is very important in the prevention and treatment of cervical cancer. In China, the cervical screening strategy needs to be improved. To explore a suitable cervical screening strategy in China, we evaluated the performance of the human papillomavirus (HPV) E6/E7 mRNA (Aptima HPV (AHPV)) assay in primary screening and different triage strategies for women undergoing routine cervical screening.MethodsA total of 10,002 women aged 35 to 65 years of age were recruited in Liaoning Province and Qingdao City, China. Specimens were tested by liquid-based cytology (LBC) and the AHPV assay, and women who tested positive on any test were referred for colposcopy. Genotyping was performed on all high-risk HPV (HR-HPV)-positive samples. Test characteristics were calculated based on histological review.ResultsWe identified 109 women with high-grade squamous intraepithelial lesion or worse (HSIL+), including six with cervical cancer. The sensitivity of AHPV was clearly higher than that of LBC (92.7 [95% CI: 87.2, 97.2] vs. 67.9 [95% CI: 59.6, 76.1], p < 0.001). The specificity of AHPV was 93.0 (95% CI: 92.5, 93.5), which was lower than that of LBC (95.2 [95% CI: 94.8, 95.6], p < 0.001). There was no statistical difference between the positive predictive value of AHPV and LBC (13.5 [95% CI: 11.2, 16.2] vs. 14.3 [95% CI: 11.4, 17.6], p = 0.695). The difference of area under the curve (AUC) values between the AHPV test (0.928 [95% CI: 0.904, 0.953]) and LBC test (0.815 [95% CI: 0.771, 0.860]) in detecting HSIL+ was statistically significant (p < 0.001). Finally, among the three triage strategies, both the sensitivity (73.4 [95% CI: 65.1, 81.7]) and AUC (0.851 [95% CI: 0.809, 0.892]) of AHPV genotyping with reflex LBC triage were the greatest.ConclusionIn summary, the AHPV assay is both specific and sensitive for detecting HSIL+ and may be suitable for use in primary cervical cancer screening in China. AHPV genotyping with reflex LBC triage may be a feasible triage strategy.

Background: Up until recently, cervical cytology was the mainstay for cervical cancer screening. However, the established association between human papillomavirus (HPV) infection and cervical cancer has led to changes in preventive strategies, with cytology being replaced by the use of high-risk HPV (hrHPV) testing and primary prevention being achieved by HPV vaccination. In this context, the role of cervical cytology is shifting to secondary triage of HPV-positive women. As vaccination is leading to decreased HPV infections and significant cervical abnormalities (CIN2+), data on the impact of HPV vaccination on cervical cytology metrics, including positive predictive value (PPV) and negative predictive value (NPV), are starting to emerge. Summary: This is a review of updates in cervical cancer screening, including the use of primary HPV testing and the impact of HPV vaccination on cytology as part of cervical cancer screening. Key Messages: Cervical cancer screening and prevention are undergoing significant changes as there is widespread implementation of HPV vaccination and hrHPV testing is becoming the entry point for secondary prevention. Optimal screening approaches and intervals in this setting are currently being analyzed including the use of cytology and other ancillary techniques for triage of positive cases, as well as the effect of vaccination on the PPV and NPV of cytology in the detection of CIN2+.

With the introduction of widespread Pap smear screening starting in the 1940s, the United States has seen at least a 50% reduction in the incidence and mortality of invasive cervical cancer. In light of the ease of sampling, the long pre-malignant phase of cervical cancer, and well-tolerated treatment options for pre-invasive disease, cervical cancer screening has served as a model for screening for other malignancies. For some women, it also serves as the cornerstone for annual routine visits with gynecologists. Both patients and gynecologists have been taught that a yearly Pap test is important, and it can serve as the backbone of care. Unfortunately, however, access to screening and treatment for cervical cancer continues to be an issue for some women in the United States. Approximately 60% of women with invasive cancer had not undergone a Pap test in the 5 years preceding their diagnosis or have never undergone a Pap test. 1 The long history of Pap tests has also taught us a number of lessons. We have learned that cytologic screening is hardly perfect. In a study by Nanda et al. 2 the sensitivity of a single test was 51%, and this was subsequently confirmed in a pooled analysis of European and Canadian studies by Cuzick et al. 3 One way to compensate for this poor sensitivity is by using serial screening; the sensitivity of cytology increases to 76% with 2 consecutive annual Pap tests and 88% with 3 consecutive tests. Just adding tests and procedures, however, is not always the answer, and most recently the pendulum has swung in the other direction. We now understand the risk of overtreating pre-invasive disease and the potential impact of overtreatment on preterm labor and neonatal morbidity and mortality. In many adolescents and young women, abnormal Pap tests and underlying disease will resolve spontaneously. Therefore, in 2009, the American College of Obstetricians and Gynecologists recommended that screening for cervical cancer start at age 21. 4 Another lesson learned is the role of human papillomavirus (HPV) in cervical cancer. High-risk (HR) HPV DNA testing has become a mainstay of cervical cancer screening over the past 10 years. Experts now recognize that more than 99% of all invasive cervical cancers are associated with 14 different HR HPV types. Currently, HR HPV testing is recommended for women with equivocal Pap tests (ASC-US) and atypical glandular Pap tests (AGC). Most importantly, it is also widely recommended in conjunction with Pap testing in women older than 30 years of age. In keeping with the lesson of not overtreating and overscreening, after negative Pap and HPV test results, an individual woman can increase her screening interval to every 3 years. Another benefit of HR HPV testing is its much higher sensitivity than Pap testing (96% vs. 53% in pooled estimates). Since 2005, 7 randomized controlled trials 5–11 have been published that evaluated HPV testing in the screening setting. These studies have largely shown improvements in the detection of pre-invasive lesions either alone or in conjunction with Pap testing. Of particular note, a recently published trial from Finland showed

BackgroundGlobally, cervical screening is moving from cytology (Pap) to HPV-based testing. Cytology-based screening has occurred for decades; therefore, engaging the screened population is critical to success of this significant paradigm...

ObjectiveThe aim of this study was to clinically evaluate the application of liquid-based cytology P16, cytologic evaluation, and high-risk human papillomavirus (HR-HPV) testing in cervical cancer screening.MethodsThis study screened 900 women, who attended the outpatient clinic, according to the exclusion criteria of study participants. The study participants’ screening results of liquid-based cytology P16, cytologic evaluation, and HR-HPV testing were analyzed. According to the pathological results of the biopsy, the efficacy of different screening strategies for the identification of high-grade lesions was evaluated.ResultsThe positive rate of p16 expression increased with the severity of cervical lesions. P16 had the highest sensitivity and negative predictive value in identifying high-grade lesions (98.45% and 99.67%, respectively). Liquid-based Papanicolaou test (LBP), on the other hand, had the lowest sensitivity (85.27%) but the highest specificity (85.88%). HR-HPV’s positive predictive value and accuracy rate were the lowest (32.77% and 70.03%, respectively). The difference was statistically significant (P < 0.05). Dual combinations of certain tests were set up for this study; P16+LBP, HPV+LBP, and P16+HPV had sensitivities of 98.45%, 96.90%, and 99.22%, and specificities of 80.29%, 63.42%, and 64.33%, respectively. The P16 screening rates of histological and liquid-based cytology approaches were 75.74%.ConclusionCompared with traditional LBP+HPV, the application of a test that solely screen for P16 or the combined screening method that involves the screening of P16 is more effective in identifying high-grade lesions.

In addition to liquid-based cytology (LBC) and HR HPV testing, p16/ki-67 dual-staining is another method for cervical cancer screening. The combination of any two methods can improve the accuracy of screening, but some cervical lesions are still missed or misdiagnosed. In this retrospective study, the significance of LBC, HR HPV testing and especially p16/ki-67 dual-staining in cervical lesion screening was evaluated with reference to histological diagnosis. At the same time, we tried to explore the value of p16/ki-67 dual-staining combined with LBC and HR HPV testing (triple detection) in improving the diagnostic specificity of CIN2+ and reducing the missed diagnosis of CIN2+ lesions. We found that p16/ki-67 dual-staining was valuable in identifying cervical CIN2+ lesions and reducing the missed diagnosis of CIN2+ in HPV negative patients. More than 96% of CIN2+ patients were positive for two or three tests of triple detection. Whole positive triple detection can effectively predict high grade cervical lesions. In conclusion, the triple detection can distinguish almost all cervical CIN2+ lesions. Our data put forward and highlight the feasibility and significance of triple detection in cervical lesion screening.

INTRODUCTION:The cost-effectiveness of Human papillomavirus (HPV)-based primary cervical screening in the Irish healthcare setting is assessed using a decision-analysis approach to inform a decision around changes to the national screening program. Current practices comprises primary screening with liquid-based cytology (LBC) followed by HPV triage, at 3-yearly intervals for ages 25 to 45 years and 5-yearly until age 60 years.METHODS:This study assessed changing the primary screening test from LBC to HPV testing, in both an unvaccinated and a vaccinated (against HPV 16/18) cohort. It considered extending the screening interval (to 5-yearly for all), the upper age limit (from 60 to 65 years) and different test sequences (four possible tests were included: HPV, LBC, partial genotyping for HPV16 or HPV 18 and the molecular biomarker p16INK4a/Ki67). A Markov-model for HPV-infection and cervical cancer was developed based on a German cervical screening model (1). The perspective of the healthcare system was adopted and a 5 percent discount rate used.RESULTS:Strategies using HPV as the primary screening test are more effective than LBC-based strategies. The optimal strategy, at a willingness-to-pay threshold of EUR45,000 per quality-adjusted life year (QALY), for the unvaccinated cohort was HPV-based primary screening with a LBC triage test, at five-yearly intervals from age 25 to 60 years. This strategy is cost saving compared with current practice and cost effective when compared to no screening, with an Incremental cost-effectiveness ratio (ICER) of EUR18,164 per QALY. The optimal strategy for the vaccinated cohort was also HPV primary screening with a LBC triage test, at five-yearly intervals from age 25 to 60 years. While more effective and cost saving compared with current practice, it would not be considered cost effective compared with no screening (ICER of EUR58,745/QALY).CONCLUSIONS:Based on our analyses, HPV-based cervical screening is more effective and cost saving compared with LBC-based screening for both vaccinated and unvaccinated cohorts in an Irish setting.

PurposeTo evaluate the diagnostic performance of the current three-step cervical cancer screening strategy in Chinese women and explore the optimized value of integrating human papillomavirus (HPV) testing, ThinPrep cytology test (TCT), and colposcopic visual inspection with acetic acid/Lugol’s iodine (VIA/VILI) for improving cervical disease detection.Patients and MethodsA retrospective study was conducted on 11,405 outpatients of Shenzhen People’s Hospital (2018–2023). Inclusion criteria were a history of sexual activity plus at least one of the following: high-risk HPV (HR-HPV) positivity, abnormal TCT results, or highly suspicious symptoms. Exclusions included prior hysterectomy, cervical cancer (CC) treatment history, pregnancy, or incomplete medical records. The diagnostic performance of HR-HPV testing, TCT, and colposcopic VIA/VILI results was evaluated using pathologically confirmed high-grade squamous intraepithelial lesion (HSIL) and CC as the reference standard. The calculated metrics comprised sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC).ResultsAmong the cohort, the positive rates were 71.56% for HR-HPV, 32.57% for abnormal cytology, and 9.34% for colposcopic VIA/VILI. For detecting HSIL/CC, the NPVs of HPV testing, TCT, and colposcopic VIA/VILI were 0.976, 0.955, and 0.965, respectively. Combined use of the three modalities achieved an NPV of 0.999 for HSIL/CC. Integrating colposcopic VIA/VILI into primary screening also reduced both false-positive and false-negative results compared with single-modality strategies.ConclusionIn this large real-world retrospective cohort, combining HPV testing, TCT, and colposcopic VIA/VILI improves the diagnostic accuracy of high-grade cervical disease (HSIL and CC), with practical feasibility for clinical application. However, this integrated approach needs prospective multi-center validation before widespread promotion in cervical cancer screening among community populations.

Cervical cancer is the third tumor in the global female cancers. A total of 130 000 cases of new cervical cancers patients were found in China every year, accounting for 28% of the world. More than 95% of cervical cancer can be prevented. In addition to human papilloma virus (HPV) vaccine immunization, we need to adopt the ideal screening method and ensure the quality of screening. At present, we still have not built our cervical cancer screening system. The screening method is still in a state of a variety of screening methods coexist. We should choose an appropriate method for cervical cancer screening based on the economic status and medical personnel technical level. Key words: Uterine cervical neoplasms; Screening; Cell biology; Human papillomavirus infection; Female

Cervical cancer is a primary cause of death in women. Human Papilloma Virus (HPV) virus is the main factor that causes cervical cancer. Therefore, risk reduction of cervical cancer is cervical cancer screening and vaccination against infection of HPV. The methods of cervical cancer screening are medical history, HPV virus detection, Pap smear detection, and small pieces of meat cutting. However, Pap smear detection is a popular technique for cervical cancer screening. In addition, the classification method is used to increase the performance of cervical cancer detection. Therefore, our research proposed method of cervical cancer detection using hybrid classification methods with risk factor data of cervical cancer and cervical cancer behavior risk data, which is divided into two stages: primary risk estimation of a chance cervical cancer and cervical cancer prediction. Firstly, the dataset was prepared to handle missing values and imbalanced data. Secondly, we select suitable attributes for model building. Finally, the dataset was used to build the model using hybrid classification methods by bagging with Random Forest. From our experiment, the model for primary risk estimation of a chance cervical cancer and cervical cancer prediction has an accuracy of 99.25% and 98.00%, respectively. The result shows that our proposed method accurately predicts cervical cancer compared to state-of-the-art methods. Therefore, it confirms that our proposed model can be applied to use for primary risk self-estimation of a chance of cervical cancer before deciding to meet a physician. Moreover, it helps the physician with diagnosis and treatment to reduce costs and the death rate.

Cervical cancer is mostly caused by high-risk Human papillomavirus HPV, with an estimation prevalence of HPV of 99.7% worldwide. The US Food and Drug Administration (FDA) approved an HPV test for primary cervical screening in 2014. An HPV-DNA test, which provides higher protection against invasive cervical carcinomas, is replacing the long-standing Pap smear as the primary method of cervical cancer screening. To explore nurses' experience and knowledge of HPV DNA testing and how screening impacts on women's health through increasing awareness and proposing actions for health education strategies. A qualitative exploratory study was conducted on a purposeful sample of 25 qualified nurses, who were all employed in regional hospitals within a gynecological department in Kirkuk, Iraq. The nurses were interviewed with a semi-structured topic guide between November 2021 and February 2022. Responses were transcribed verbatim, translated into English and analysed using a content thematic analysis approach. Four themes with associated sub-themes emerged following coding and peer review. Participants had lack of experience and fragmented knowledge of HPV DNA testing/screening. Culturally sensitive resources for patients and training for nurses was identified key requirements. Currently, there are no facilities for a HPV testing/screening services available in Iraq. The role of nurses undertaking HPV screening is not established and yet nurses represent the largest sector of health professionals. The dissemination of a collaborative HPV screening training programme to include clinical competence and knowledge for nurses and gynaecologists may improve knowledge, and could also be effective in improving patient awareness and engagement with cervical health.

Background:The HPV FOCAL Trial is a RCT comparing human papilloma virus (HPV) with Liquid Based Cytology (LBC) screening for cervical cancer. Results are presented for the comparison of the Safety and Control arms after two rounds.Methods:HPV FOCAL included randomisation of women aged 25–65 into the Safety arm, where they were initially screened with HPV and the Control arm, where they received entry screening with LBC, with both arms screened again with LBC at 24 months.Results:There are 6203 (Safety) and 6075 (Control) women included in this analysis. For the Safety vs Control arms, Round 1 screening resulted in increased detection of cervical intraepithelial neoplasia 2 or worse (CIN2+),15.3 vs 10.4 per 1000, RR=1.48 (95%CI=1.08–2.03) and higher colposcopy referral rates, 5.6% vs 3.2%. LBC screening at 24 months resulted in similar colposcopy referral rates, 1.5% vs 1.9%, and decreased CIN2+ detection, 2.0 vs 4.7 per 1000, RR=0.43 (95%CI=0.21–0.88) in the Safety vs Control arms. CIN2+ detection and colposcopy referral rates declined with increasing age in both arms. One round of HPV screening detected similar levels of CIN2+ as two rounds of LBC screening.Interpretation:CIN2+ detection at 2 years was lower in those screened by HPV, indicating an improved 2-year negative predictive value of the HPV test.