Cervical Cancer Screening Methods Research Articles

Screening Methods for Cervical Cancer.

Cervical cancer seriously affects the health of women worldwide. Persistent infection of high-risk HPV (Human Papilloma Virus) can lead to cervical cancer. There is a great need for timely and efficient screening methods for cervical cancer. The current screening methods for cervical cancer are mainly based on cervical cytology and HPV testing. Cervical cytology is made of Pap smear and liquid-based cytology, while HPV testing is based on immunological and nucleic acid level detection methods. This review introduces cervical cancer screening methods based on cytology and human papillomavirus testing in detail. The advantages and limitations of the screening methods are also summarized and compared.

Acceptability of self-collected vaginal samples for human papillomavirus testing for primary cervical cancer screening: comparison of face-to-face and online recruitment modes

BackgroundThis study aimed to assess the acceptability and attitudes of women towards human papillomavirus (HPV) self-sampling and compare the effectiveness of two delivery modes utilising face-to-face and online website for cervical cancer screening in Hong Kong.MethodsWomen aged 30–65 years were invited to participate by distributing the study information pamphlets at the specialist clinics of a regional acute hospital. Those who were interested in participating were given the option to join directly face-to-face or through an online website. All participants provided informed consent and received self-sampling kits and acceptability questionnaires either immediately (face-to-face) or through the post after registering at the website (online). All participants were requested to collect their own vaginal samples using a swab which was then brushed on a DNA sample storage card and returned to the hospital either in person or by post. The self-collected samples were tested for high-risk HPV using the Sentis™ HPV assay, a validated isothermal nucleic acid amplification real-time fluorescent detection assay. The primary outcome was the uptake rate of HPV self-sampling.ResultsOf the 1998 women recruited (1200 face-to-face, 798 online), 1377 returned their samples, giving an overall uptake rate of 68.9%. The uptake rate was significantly greater in the face-to-face mode than in the online mode (74.6% vs. 60.4%, p < 0.001). The median age of the participants was 49 years, 43.7% were never or under-screened, and 7.1% had high-risk HPV detected. Overall, 82.1% of the participants reported self-sampling convenient, and 79.3% were not embarrassed when collecting self-samples. However, only 49.8% were confident that they had collected the self-samples correctly. Most (91.1%) of the participants expressed willingness to perform self-sampling again, mostly because it was simple (79.2%) and quick (56.3%).ConclusionsHPV self-sampling can serve as an alternative primary screening method for cervical cancer in Hong Kong, especially for individuals who have not been adequately screened in the past. Both face-to-face and online website recruitment were associated with high acceptability, emphasising the potential benefits of utilising different platforms and strategies for reaching diverse populations.

206 Cervical Cancer Disparities: Knowledge, Screening and Willingness to adopt testing modalities among Hispanic/Latinx Women in Lake County, Indiana

OBJECTIVES/GOALS: There are notable disparities in cervical cancer screening. Theobjective of this study was to examine knowledge, screening practices, attitudes towards cervical cancer screening, and willingness to adopt screening innovations such as self-sampling and HPV rapid testing for cervical cancer among Hispanic women in Lake County, Indiana. METHODS/STUDY POPULATION: This mixed-methods study encompassed an online cross-sectional survey (n=231) and in-depth interviews (n=9) of individuals with a cervix aged 21-65 residing in Lake County, Indiana. Outcome variables focused on cervical cancer knowledge, willingness to adopt self-sampling, and willingness to adopt HPV rapid testing. Descriptive statistics included frequencies and percentages. A cervical cancer knowledge score was computed from 7 questions. Scores below the mean 3.62 were labeled ‘low’ while higher scores were ‘high’. We also examined associations between demographic and outcome variables. Quantitative analysis was conducted using SPSS software. Qualitative analysis was conducted using NVIVO software to thematically analyze interviews using deductive and inductive coding techniques. RESULTS/ANTICIPATED RESULTS: Majority of participants identified as Hispanic (58%), aged 31 or older (58%). While 80.5% reported being screened for cervical cancer, only 44.6% demonstrated ‘high' cervical cancer knowledge. 89.6% felt screening is important as emphasized in qualitative findings for its preventive value. Over half were willing to take their vaginal swab in clinic (55.8%) and at home (51.9%). However, among the Hispanic/Latinx groups reluctance to adopt self-sampling was notable (56.7% in clinic and 62.7% at home). Qualitative analysis revealed concerns about test accuracy. Willingness to use a hypothetical HPV rapid had higher acceptance (69.7%), with 52.2% in the Hispanic/Latinx group. Qualitative findings highlight benefits like increased screening access, comfort, and convenience offered by an HPV rapid test. DISCUSSION/SIGNIFICANCE: Hispanic/Latinx women in the sample were less willing to adopt cervical cancer screening methods such as self-sampling and rapid testing compared to non-Hispanic whites. Despite being considered beneficial for testing among vulnerable populations, our study found limited acceptance from these populations for various reasons.

Abstract 7290: Novel plasmid-based screening method for cervical cancer

Abstract Introduction: Alabama (AL) is tied for third-highest incidence rate and has second-highest death rate of cervical cancer as of 2020. Globally, cervical cancer has the fourth-highest incidence among cancers in women; 90% of deaths from cervical cancer in 2020 occurred in low- and middle-income (LMIC) countries. Inhibitor of differentiation/DNA binding 1 (Id1) expression correlates with tumorigenesis, clinical grade/stage, and aggressiveness of cervical cancer. Thus, Id1 expression could be exploited in novel screening approaches that aim to improve survival rates of cervical cancer in LMIC and clinically underserved settings. As a first step in developing an Id1-based screening approach, these preclinical studies utilized a plasmid that induces expression of a secreted reporter enzyme (secreted embryonic alkaline phosphatase, SEAP), controlled by the Id1 promoter sequence (pId1-SEAP). These studies examined relationships between Id1 expression and kinetics of reporter expression following plasmid transfection to detect human cervical cancer cells. Methods and Results: To confirm the relevance of Id1 as a target in cervical cancer, immunohistochemical staining for Id1 was performed on a human cervical cancer tissue microarray. Western blotting was performed to determine Id1 expression in human cervical cancer cell lines (HeLa, SiHa, CaSki). Optimal transfection conditions with pId1-SEAP were determined experimentally for each line, and then media was sampled through a 48-hour period post-transfection to quantify reporter SEAP expression. Immunohistochemical stain for Id1 showed that early stage and late stage human cervical cancer tissues expressed significantly (p &amp;lt; 0.05) higher levels of Id1 compared to normal tissues, with stain optical density values being 3e5±1e5 for early and late stage compared to 3e4±3e4 for normal tissues (early stage p=0.0001, late stage p=0.0002). Western blot for Id1 in HeLa, SiHa, and CaSki lines showed that all three positively expressed Id1, with Beta-actin-normalized expression values of 0.78±0.12, 1.12±0.05, and 0.76±0.08, respectively. The cell lines transfected with pId1-SEAP expressed SEAP at rates significantly higher than control cells, with the highest rates of production seen during the 36-48-hour post-transfection period. Rates of SEAP production (counts/hour) during this time period were 1e4±3e3 (p=0.0278), 8e2±1e2 (p=0.0834), and 3e2±5e1 (p=0.0683) for transfected HeLa, SiHa, and CaSki cells, respectively. Conclusions: The pId1-SEAP system enabled sensitive detection of cervical cancer cells. These preliminary data support future studies evaluating the in vivo performance of the system in preclinical models of early stage cervical cancer. Further development of this approach could enable sensitive and reliable detection of cervical cancer during early stages when treatment is most effective. Citation Format: Abbigael Eli, Yolanda Hartman, Benjamin B. Kasten, Rebecca Arend, Jason Warram. Novel plasmid-based screening method for cervical cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7290.

Extended HPV typing test performed better predict value for CIN2+ among elderly women in China

ObjectiveThe aim of this study was to examine the cervical cancer screening practices among women residing in Lingang New District of Shanghai. Moreover, the study aimed to delve into the characteristics of HPV infection and cervical lesions in older women (≥60 years old), seeking for more effective method for cervical cancer screening. MethodsThis is a cross-sectional study enrolled women who were referred to colposcopy and cervical histological examination due to abnormal cytology or HPV tests from Shanghai Sixth People's Hospital between January 2018 and December 2022. ResultsA total of 1,931 women (mean age: 41.8 ± 12.5, range: 18–88 years old) were enrolled, 119 individuals aged ≥ 60 and 1732 aged <60. The infection rates of HPV52, 33, 35, 56, 26 and 81 were significantly higher in the elderly group. Multiple HPV infection rates were also higher in this group and were associated with cervical lesions. The probability of LSIL, HSIL and Ca in women over 60 years old was significantly higher compared to women under 60. The top three HPV genotypes in elderly women with CIN2+ were HPV16, 52, and 58. The Yoden index was higher for extended typing for HPV 31/33/45/52/58(0.41) compared to cytology(0.29), high risk HPV without specific typing(0.07), cotest(cytology and high risk HPV, 0.06 or 0.30), or the current shunt strategy(0.07). ConclusionsElderly women still need to continue cervical cancer screening, and extended typing test for HPV16/18/31/33/45/52/58 is a more effective method for this age group.

The risk of vaginal, vulvar and anal precancer and cancer according to high-risk HPV status in cervical cytology samples.

High-risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five-year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV-positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV-negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV-positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non-cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow-up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high-risk groups and acceptable risk thresholds.

Cervical cancer screening program in Indonesia: is it time for HPV-DNA tests? Results of a qualitative study exploring the stakeholders’ perspectives

ObjectivesCervical cancer is a significant public health concern in Indonesia, and effective screening methods are necessary to improve the detection and reduce mortality. This study aimed to explore the perspectives of high-level stakeholders involved in cervical cancer screening in Indonesia and whether the use of human papillomavirus-deoxyribonucleic acid (HPV-DNA) methods for cervical cancer screening is acceptable in Indonesian settings.MethodsA qualitative research approach guided by realist evaluation was applied using focus group discussions (FGDs) between December 2021 and February 2022, conducted with stakeholders involved in cervical cancer screening in Indonesia. They were representatives of practitioners and policymakers involved in the screening, and were recruited through purposive recruitment. The data were analysed using inductive approach of thematic analysis.ResultsThe analysis of two FGDs with 29 participants identified four main themes: (i) Visual inspection with acetic acid (VIA) method as the most common modality used for cervical cancer screening, (ii) the applied screening programs in the community, (iii) the perceived challenges on the screening program, such as limitations of the National Health Insurance benefits package and a lack of regulations regarding screening procedures, and (iv) the possibilities of HPV-DNA testing as another modality for cervical cancer screening. Incorporating HPV-DNA testing also needs to ensure the capacity of the workers and the readiness of healthcare facilities.ConclusionAlthough HPV-DNA testing is a promising modality, challenges on the cervical cancer screening in Indonesia remain on the coverage, accessibility of the tools in practice and the women’s awareness towards the screening. Ultimately, the findings of this study would help inform policies to improve cervical cancer screening programs in Indonesia.

Sitologi Berbasis Konvensional dibandingkan dengan Cairan sebagai Skrining Kanker Servik : Sebuah Sistematik Review

Worldwide, there are 2.784 million women aged 15 years and over who are at risk of cervical cancer, and about 527,624 new cases of cervical cancer are diagnosed each year. Cervical cancer ranks as the fourth leading cause of cancer in women worldwide, and is the second most common cancer in women between the ages of 15 and 44. Cervical cancer can have devastating effects with very high costs, socially, and economically, affecting women in their productive years. Screening with routine cytology, using Papanicolaou (Pap) staining, has a major impact on the incidence of cervical cancer in many countries. In developed countries, but not in any developing country although its use is widespread. The use of conventional cytology as the primary test method has been replaced by the use of liquid-based cytology in many countries that have organized cervical cancer screening programs, such as the United Kingdom, the Netherlands, and Denmark. The main advantages of using liquid-based cytology instead of primary conventional cytology are that it facilitates reflex testing (i.e., residual material can be tested for the presence of human papilloma virus if borderline/slightly dicariotic smears are present) and reduces the number of slides of unsatisfactory quality. This literature review study aims to further examine how conventional cytology compares to liquid-based cytology as a method used in conducting cervical cancer screening. The journal in this review literature uses 3 databases including Google Scholar, PubMed, and Science Direct using the keywords "liquid based cytology", "conventional cytology" and "cervical cancer screening". Literature searches are adjusted based on inclusion and exclusion criteria. The search results were obtained by 10 international journals. Results show that both conventional and liquid-based cytology are effective methods for cervical cancer screening. Although liquid-based cytology may have some advantages over conventional cytology, both methods have proven effective for detecting cervical pathologies.Worldwide, there are 2.784 million women aged 15 years and over who are at risk of cervical cancer, and about 527,624 new cases of cervical cancer are diagnosed each year. Cervical cancer ranks as the fourth leading cause of cancer in women worldwide, and is the second most common cancer in women between the ages of 15 and 44. Cervical cancer can have devastating effects with very high costs, socially, and economically, affecting women in their productive years. Screening with routine cytology, using Papanicolaou (Pap) staining, has a major impact on the incidence of cervical cancer in many countries. In developed countries, but not in any developing country although its use is widespread. The use of conventional cytology as the primary test method has been replaced by the use of liquid-based cytology in many countries that have organized cervical cancer screening programs, such as the United Kingdom, the Netherlands, and Denmark. The main advantages of using liquid-based cytology instead of primary conventional cytology are that it facilitates reflex testing (i.e., residual material can be tested for the presence of human papilloma virus if borderline/slightly dicariotic smears are present) and reduces the number of slides of unsatisfactory quality. This literature review study aims to further examine how conventional cytology compares to liquid-based cytology as a method used in conducting cervical cancer screening. The journal in this review literature uses 3 databases including Google Scholar, PubMed, and Science Direct using the keywords "liquid based cytology", "conventional cytology" and "cervical cancer screening". Literature searches are adjusted based on inclusion and exclusion criteria. The search results were obtained by 10 international journals. Results show that both conventional and liquid-based cytology are effective methods for cervical cancer screening. Although liquid-based cytology may have some advantages over conventional cytology, both methods have proven effective for detecting cervical pathologies.

Divergent effects of switching from cytology to HPV-based screening in the Nordic countries.

Cervical cytology has been the primary method of cervical cancer screening for decades. Tests that detect viral HPV are shown in several randomized trials to provide better protection against cancer compared with cytology. HPV-based screening has been implemented alongside cytology in the Nordic countries for several years. The aim of this study was to compare cytology and HPV-based screening in the colposcopy referrals and detection rates of cervical lesions. Individual-level screening data from Finland, Iceland, Norway and Sweden were harmonized and aggregated locally. We utilized data for tests taken during years 2015-17 and biopsies taken during years 2015-19 to allow 24 months of follow-up. Age-standardized estimates and age-adjusted risk ratios for six different outcomes of screening management were calculated. The age-standardized colposcopy rates were higher in HPV-based testing compared with cytology in Finland (3.5% vs. 0.9%) and Norway (6.0% vs. 4.1%) but lower in Sweden (3.7% vs. 4.9%). The relative detection rate of cervical intraepithelial neoplasia grade 2 and above in HPV-based testing compared with cytology was highest in Finland (RR 2.37, 95% CI 2.13-2.63) and Norway (RR 1.66, 95% CI 1.57-1.72) while in Sweden the difference was not statistically significant (RR 0.98, 95% CI 0.95-1.00). The effects of implementing HPV screening varied by country as different screening algorithms were implemented. HPV-based screening increases colposcopy rates mainly through referrals from increased repeat testing and detection rate is therefore significantly higher compared with cytology. Monitoring of these indicators in subsequent rounds of HPV-based screening remains essential.

Retracted: NECScanNet: Novel Method for Cervical Neuroendocrine Cancer Screening from Whole Slide Images

Retracted: NECScanNet: Novel Method for Cervical Neuroendocrine Cancer Screening from Whole Slide Images

High-grade cervical lesions diagnosed by JAM3/PAX1 methylation in high-risk human papillomavirus-infected patients.

Currently, traditional cervical cancer screening methods, such as high-risk human papillomavirus testing and liquid based cytology (LBC), still possess limitations. This study aims to identify new diagnostic biomarkers to achieve the goal of "precision screening" via exploring the clinical value of DNA methylation [ΔCtP: paired box gene 1 (PAX1)and ΔCtJ: junctional adhesion molecule 3 (JAM3)] detection in cervical exfoliated cells for the diagnosis of high-grade cervical lesions. A total of 136 patients who underwent gynecological examinations in the vaginal room of the Department of Gynecology at the Third Xiangya Hospital of Central South University from June 2021 to June 2022 were retrospectively studied. Among them, 122 patients had non-high-grade cervical lesions, and 14 patients had high-grade cervical lesions. The variables included general information (age, body mass index, and menopause status), LBC, high-risk human papillomavirus, cervical tissue pathology, vaginal examination results, and the ΔCt values of JAM3 and PAX1 gene methylation. Logistic regression analysis was used to identify the factors affecting the diagnosis of high-grade cervical lesions, followed by correlation analysis and construction of a conditional inference tree model. Logistic regression analysis showed that the methylation ΔCt values of PAX1 and JAM3 genes and LBC detection results were statistically significant between the high-grade cervical lesions group and the non-high-grade cervical lesions group (all P<0.05). Correlation analysis revealed a negative correlation between cervical pathological changes and ΔCtP (r=-0.36, P<0.001), ΔCtJ (r=-0.448, P<0.001), LBC (r=-0.305, P<0.001), or bacterial diversity (r=-0.183, P=0.037). The conditional inference tree showed that when ΔCtJ>10.13, all of patients had non-high-grade cervical lesions, while ΔCtP>6.22, the number of non-high-grade lesions accounted for 97.5% (117/120), and high-grade lesions accounted for only 2.5% (3/120). When ΔCtJ>8.61 and LBC were atypical squamous cell of undetermined significance or negative for intraepithelial lesions or malignancy (NILM), 105 (99.1%) patients were non-high-grade cervical lesions, only 1 (0.9%) patient was high-grade lesion. When the results of LBC were high-grade lesions, only 9 patients' histopathological examination was the high-grade lesions and 3 non-high-grade lesions. When LBC indicated low-grade lesions, atypical squamous cell of undetermined significance, no intraepithelial lesions, and ΔCtP>6.22, 117 (97.5%) of patients' histopathological examination was the non-high-grade lesions. The JAM3/PAX1 gene methylation test can be used independently for the stratified diagnosis of high-grade/non-high-grade cervical lesions in women with high-risk human papillomavirus infection, independent of the cytological results of cervical excision. The JAM3/PAX1 gene methylation test can also be used in combination with LBC to make up for the shortcomings of low sensitivity of LBC. In addition, the application of methylation kit in large-scale cervical cancer screening in the future will be good to the detection of more patients with high-grade cervical lesions, and achieve early screening and early treatment for cervical lesions/cancer.

OP81 Cost Effectiveness Of Human Papillomavirus Extended Genotyping For Cervical Cancer Screening In Singapore

IntroductionThe World Health Organization recommends the human papillomavirus (HPV) test for cervical cancer screening. HPV partial genotyping (PGT) identifies HPV16 and HPV18 individually and the 12 other high-risk HPV genotypes (hrHPV) collectively. In contrast, HPV extended genotyping (XGT) identifies six hrHPV individually (HPV16,18,31,45,51, and 52) and the other eight in three groups (HPV33/58, HPV56/59/66, and HPV35/39/68). XGT allows better risk stratification for patient management and monitoring of persistent same-genotype infections (PSGI), which convey a higher risk for cervical cancer. This study compared the cost, quality-adjusted life-years (QALYs), and resource use of XGT with PGT when used as the primary cervical cancer screening method in Singapore.MethodsA discretely integrated condition event simulation was developed for screening 500,122 women aged 30 to 69 years over five years from the health system perspective, using a three percent annual discount. For XGT, women with HPV35/39/51/56/59/66/68 and reflex cytology of atypical squamous cells of undetermined significance were recalled for a repeat screening in one year, instead of the immediate colposcopy referral that occurs with PGT. At repeat screening, colposcopy was only provided for women with PSGI on XGT. Published data from Singapore were used for inputs and supplemented with data from international literature. Deterministic and probabilistic uncertainty analyses were conducted. Scenario analysis was conducted to simulate various HPV burdens among women. XGT was cost effective when the incremental cost-effectiveness ratio (ICER) relative to PGT was below SGD100,000 (USD118,906) (gross domestic product per capita in 2021).ResultsXGT was cost effective relative to PGT (ICER SGD16,370 [USD19,465]), with fewer colposcopies (n=7,130; 19%), liquid-based cytology tests (n=6,027; 7%), and clinic consultations (n=9,787; 2%) but more HPV tests (n=2,446; 0.5%). The ICER was most sensitive to the relative cost of XGT and the cost of PGT. XGT remained cost effective in one-way sensitivity analysis in all 1,000 probabilistic uncertainty simulations and in scenario analysis with various HPV burdens.ConclusionsXGT can provide a cost effective, risk-based approach to primary cervical cancer screening, with lower resource utilization than PGT.

Evaluating the economic screening of cervical cancer using IVA, HPV DNA, and histology methods: Systematic review

Background: Cervical cancer is a common malignancy causing cancer-related deaths worldwide. Evidence suggests that adequate screening can reduce cervical cancer-related deaths. Screening for cervical cancer can be done using Visual Inspection of Acetic Acid (VIA), HPV DNA and cytology. The economic burden of cancer patients is substantial ranging from US$8,066 to 22,888 per patient. Health cost effectiveness was comparative in the analysis of costs and consequences for the three screening methods. VIA is the most cost-effective primary screening test for cervical cancer. Purpose: To review the research results of a full economic evaluation to encourage the specific cervical cancer screening methods used to enhance the detection of precancerous lesions in women's cervix. Method: This systematic review used the PRISMA ScR framework with a literature search using 3 databases, namely Pubmed, Wiley, and Google Scholar, with years of publication from 2009 – 2023. The data that has been obtained is carried out by critical appraisal using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Results: Based on the search for 3,973 selected articles, 7 match the inclusion criteria. This systematic review discovered three major themes: the utility value of health status, cost and analysis. Conclusion: The most cost-effective cervical cancer screening is by VIA. HPV DNA and pap smear based cytology techniques have been reported to show high sensitivity and specificity respectively including being expensive and resource intensive. In contrast the VIA technique has moderate sensitivity and specificity but is less expensive Various developed countries have used Pap or HPV DNA cytology tests as the main screening method, which can lead to a 50-70% reduction in cervical cancer incidence, while in developing countries using VIA tests as a cervical cancer screening method.

Discussion on cervical cytology in postmenopausal women.

Considering the cervix at the climacteric period, important changes take place in the morphology of the epithelium and stroma due to hypoestrogenism. Therefore, the aim of the present study was to compare the presence of transformation zone cells in the cervix of premenopausal and postmenopausal women. In a private laboratory in São Paulo (Brazil) a retrospective analysis of cervical cytology results was performed. A total of 1,026,671 satisfactory cytology tests were evaluated between January 2010 and December 2015. A marked decline in transformation zone cells with age was evident, with a greater decrease in the ≥50 years age groups. Only 35% of women ≥50 years of age had transformation zone cells in cytology, while in those <50 years, the figure was 67.5% (P<0.001). The prevalence of negative cytological results in these two age groups was respectively 89.9% and 95.3%; however, it was observed that the most serious cytological results occurred in the group after menopause. Although cytology is the recommended screening method for cervical cancer in Brazil, the low number of transformation zone cells in cytology in menopausal patients could be less sensitive for screening of dysplasia and cancer. So, we suggest routine high-risk HPV DNA testing, when possible, given that this test is considered more sensitive for detecting cervical lesions in this group of patients. When HPV DNA testing is not possible, cytology should be collected, and for cytology sampling we suggest regular topical estrogenization and use of appropriate technique.

Understanding the cervical cancer self-collection preferences of women living in urban and rural Rwanda.

Cervical cancer is a leading cause of cancer among women in low- and middle-income countries. Women in Rwanda have high rates of cervical cancer due to limited access to effective screening methods. Research in other low-resource settings similar to Rwanda has shown that HPV-based self-collection is an effective cervical cancer screening method. This study aims to compare the preferences of Rwandan women in urban and rural settings toward self-collection and to report on factors related to self-collection amenability. A cross-sectional survey was conducted from June 1-9, 2022. Women were recruited from one urban and one rural clinic in Rwanda. Women were eligible for the study if they were ≥ 18 years and spoke Kinyarwanda or English. The survey consisted of 51 questions investigating demographics and attitudes towards self-collection for cervical cancer screening. We reported descriptive statistics stratified by urban and rural sites. In total, 169 urban and 205 rural women completed the survey. The majority of respondents at both sites had a primary school or lower education and were in a relationship. Both urban and rural respondents were open to self-collection; however, rates were higher in the rural site (79.9% urban and 95.6% rural; p-value<0.001). Similarly, women in rural areas were more likely to report feeling unembarrassed about self-collection (65.3% of urban, 76.8% of rural; p-value<0.001). Notably, almost all urban and rural respondents (97.6% urban and 98.5% rural) stated they would go for a cervical cancer pelvic examination to a nearby health center if their self-collected results indicated any concern (p-value = 0.731). Rwandan women in both urban and rural areas largely support self-collection for cervical cancer screening. Further research is needed to better understand how to implement self-collection screening services in Rwanda.

HPV16 E7 oncoprotein test as a triage strategy for HPV16-positive women in cervical cancer screening: long-term follow-up outcome.

Colposcopy is recommended once human papillomavirus (HPV)16/18 infection is detected. However, not all HPV16/18-positive women will necessarily develop cervical lesions. Therefore, this study aimed to investigate the application of quantitative HPV16 E7 oncoprotein detection as a cervical cancer screening method for more efficient screening while minimizing unnecessary colposcopy. E7 oncoprotein (HPV16) was quantitatively detected in cervical exfoliated cells of HPV16-positive women. The levels of HPV16 E7 oncoprotein in different degrees of cervical lesions were compared, and the optimal cut-off value for identifying HSIL+ was determined by receiver operating characteristic (ROC) curve analysis. With a pathological diagnosis as the gold standard, the sensitivity (SEN), specificity (SPE), positive predictive value (PPV), negative predictive value (NPV), and Kappa value were calculated to verify the diagnostic value of the method. Women diagnosed with low-grade squamous intraepithelial lesions (LSIL) and normal women were followed up for 5 years to evaluate the predictive value of HPV16 E7 protein for disease progression/persistent infection. The expression level of HPV16 E7 oncoprotein was positively correlated with the degree of the cervical lesion (r = 0.589, P < 0.01). The area under the ROC curve (AUC) was 0.817 (confidence interval: 0.729-0.904). The cut-off value of E7 oncoprotein for identifying HSIL+ was 8.68 ng/ml. The SEN, SPE, PPV, NPV, and Kappa values of HPV16 E7 oncoprotein for the identification of HSIL+ were 87.1%,70.0%, 87.1%, 70.0%, and 0.571, respectively, which were higher than those of ThinPrep cytology test (TCT). The SEN, SPE, PPV, and NPV of HPV16 E7 oncoprotein in predicting disease progression/persistent infection were 93.75%, 91.30%, 88.24%, and 95.45%, respectively. The quantitative detection of HPV 16 E7 oncoprotein can not only accurately screen cervical lesions but also achieve efficient colposcopy referral. Additionally, HPV16 E7 oncoprotein can accurately predict the progression of cervical lesions and persistent HPV infection.

Concordance of Primary Human Papillomavirus Testing Among Clinicians and Patients: A Systematic Review.

Objective: Primary high risk human papilloma virus (hrHPV) testing is recommended as first-line screening for cervical cancer. Testing involves either a clinician-collected or a self-collected cervicovaginal swab. This study examines concordance between methods of collection of primary HPV testing. Methods: Ovid MEDLINE, Ovid Embase, and Cochrane were searched for relevant studies on self-collected and clinician-collected primary HPV testing published before December 31, 2022. English-language studies for primary HPV testing of average-risk patients were included. Studies conducted in screening settings rather than colposcopy clinics, that used standard devices for HPV collection, and that directly compared methods of collection were included. Outcomes were concordance and kappa between paired samples, and rate of HPV detection in self-collected and clinician-collected samples. Results: A total of 2381 studies were screened, of which 228 were included for full-text evaluation. Thirty-six studies, including 23,328 individuals screened, met the inclusion criteria. The rate of HPV detection ranged from 4.7% to 63% for self-collection and from 3.7% to 62% for clinician-collection. The concordance ranged from 78.2% to 96.9%, and kappa had substantial agreement for 26 of the 36 studies and moderate agreement for 7 of the 36 studies. Conclusions: This study directly compares clinician-collected and self-collected primary HPV screening rates. Studies were conducted in methods which are widely reproducible in the primary care setting. Primary HPV self-collection is a reliable and accurate method for cervical cancer screening.

Use of Virus Genotypes in Machine Learning Diagnostic Prediction Models for Cervical Cancer in Women With High-Risk Human Papillomavirus Infection

High-risk human papillomavirus (hrHPV) is recognized as an etiologic agent for cervical cancer, and hrHPV DNA testing is recommended as the preferred method of cervical cancer screening in recent World Health Organization guidelines. Cervical cancer prediction models may be useful for screening and monitoring, particularly in low-resource settings with unavailable cytological and colposcopic examination results, but previous studies did not include women infected with hrHPV. To develop and validate a cervical cancer prediction model that includes women positive for hrHPV infection and examine whether the inclusion of HPV genotypes improves the cervical cancer prediction ability. This diagnostic study included diagnostic data from 314 587 women collected from 136 primary care centers in China between January 15, 2017, and February 28, 2018. The data set was separated geographically into data from 100 primary care centers in 6 districts for model development (training data set) and 36 centers in 3 districts for model validation. A total of 24 391 women identified with positive hrHPV test results in the cervical cancer screening program were included in the study. Data were analyzed from January 1, 2022, to July 14, 2022. Cervical intraepithelial neoplasia grade 3 or worse (CIN3+) was the primary outcome, and cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was the secondary outcome. The ability of the prediction models to discriminate CIN3+ and CIN2+ was evaluated using the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. The calibration and clinical utility of the models were assessed using calibration plots and decision curves, respectively. After excluding women without screening outcomes, the study included 21 720 women (median [IQR] age, 50 [44-55] years). Of 14 553 women in the training data set, 349 (2.4%) received a diagnosis of CIN3+ and 673 (4.6%) of CIN2+. Of 7167 women in the validation set, 167 (2.3%) received a diagnosis of CIN3+ and 228 (3.2%) of CIN2+. Including HPV genotype in the model improved the AUROC by 35.9% for CIN3+ and 41.7% for CIN2+. With HPV genotype, epidemiological factors, and pelvic examination as predictors, the stacking model had an AUROC of 0.87 (95% CI, 0.84-0.90) for predicting CIN3+. The sensitivity was 80.1%, specificity was 83.4%, positive likelihood ratio was 4.83, and negative likelihood ratio was 0.24. The model for predicting CIN2+ had an AUROC of 0.85 (95% CI, 0.82-0.88), with a sensitivity of 80.4%, specificity of 81.0%, positive likelihood ratio of 4.23, and negative likelihood ratio of 0.24. The decision curve analysis indicated that the stacking model provided a superior standardized net benefit when the threshold probability for clinical decision was lower than 23% for CIN3+ and lower than 17% for CIN2+. This diagnostic study found that inclusion of HPV genotypes markedly improved the ability of a stacking model to predict cervical cancer among women who tested positive for hrHPV infection. This prediction model may be an important tool for screening and monitoring cervical cancer, particularly in low-resource settings.

Determinants of cervical cancer screening adherence among rural women of Chengalpattu district

Background: Cervical cancer is the second most common cancer among women in India even though it is a vaccine preventable disease. Women ever undergone a screening for cervical cancer in India is only 1.7% in rural (NFHS-5). The focus of this study was to identify the factors affecting cervical cancer screening among rural women of Chengalpattu district. Methods: It is a community based cross sectional study conducted in 12 villages coming under field practicing areas of rural health training centre of Chettinad Hospital and Research Institute in Chengalpattu district. Sampling was done by using Simple random sampling method and our sample size was 220. A pre-tested, semi-structured questionnaire was used for data collection. The collected data was entered in Microsoft Office Excel and analysis was done using SPSS software version 21. Results: The Mean (SD) age of the study participants was 45±10.17 years. Among all the participants, 181 (82.3%) were unaware about any method of cervical cancer screening. Factors that are barriers to cervical cancer screening includes feeling of being healthy (79.6%), fear of finding out cancer (71.9%), anticipation of pain (68.1%). Conclusions: Present study found out that most study participants were unaware about the methods of cervical cancer screening. It is important to educate women about cervical cancer screening methods to overcome barriers.

An integrated isothermal nucleic acid amplification test to detect HPV16 and HPV18 DNA in resource-limited settings.

High-risk human papillomavirus (HPV) DNA testing is widely acknowledged as the most sensitive cervical cancer screening method but has limited availability in resource-limited settings, where the burden of cervical cancer is highest. Recently, HPV DNA tests have been developed for use in resource-limited settings, but they remain too costly for widespread use and require instruments that are often limited to centralized laboratories. To help meet the global need for low-cost cervical cancer screening, we developed a prototype, sample-to-answer, point-of-care test for HPV16 and HPV18 DNA. Our test relies on isothermal DNA amplification and lateral flow detection, two technologies that reduce the need for complex instrumentation. We integrated all test components into a low-cost, manufacturable platform, and performance of the integrated test was evaluated with synthetic samples, provider-collected clinical samples in a high-resource setting in the United States, and self-collected clinical samples in a low-resource setting in Mozambique. We demonstrated a clinically relevant limit of detection of 1000 HPV16 or HPV18 DNA copies per test. The test requires six user steps, yields results in 45 min, and can be performed using a benchtop instrument and minicentrifuge by minimally trained personnel. The projected per-test cost is <$5, and the projected instrumentation cost is <$1000. These results show the feasibility of a sample-to-answer, point-of-care HPV DNA test. With the inclusion of other HPV types, this test has the potential to fill a critical gap for decentralized and globally accessible cervical cancer screening.