Cervical Cancer Screening Study Research Articles

Cervical Cancer Visual Screening Experience in the Republic of Tajikistan

OBJECTIVES: To study the results of the first pilot study of organized visual cervical cancer (CC) screening for the detection of precancerous pathology of the cervix in two pilot districts of the Republic of Tajikistan. STUDY DESIGN: In this cross-sectional study, the target group included healthy women of reproductive age (30-49 years) from Kushoniyon and B. Gafurov Districts who underwent visual screening. The total study population was 72,574 out of which 68,391 (94.3%) visited primary healthcare facilities for visual inspection with Lugol’s Iodine (VILI). A total of 2958 women with suspicious tests for cervical intraepithelial neoplasia (CIN) were identified (4.3%) and sent to the reproductive health care centers for further diagnostics. Post-screening diagnostic tests were performed to specify cervical lesions, which included colposcopy with acetic acid (VIA) visual inspection, cytology, and biopsy with histological examination. HPV testing wasn’t included in the diagnostic protocol due to its high cost. RESULTS: A total of 164 histologically confirmed cases of CIN were identified (0.25% of number of women screened). The detection rate of precancerous pathology was 26.9 per 100,000 female population, which is 8.2 times higher than the detection rate of CC. All patients regardless of CIN degree underwent loop electrosurgical excision (LEEP)/conization. In the follow-up period (6-48 months), complete recovery after 136 LEEP, 21 conizations, and 7 hysterectomies were observed in 97% (5 recurrences of non-invasive disease). CONCLUSION: The visual screening showed high efficiency in detecting CIN. The positive experience suggests the implementation of this program nationwide.

Current Status of Machine Learning and Artificial Intelligence in Cervical Cancer Screening and Diagnosis: A Systematic Review

Background: Cervical cancer poses a substantial global health challenge, predominantly affecting underprivileged countries. The limitations of current screening methods, such as cytology and visual examination, underscore the need for improved techniques. Artificial intelligence (AI) and machine learning (ML), particularly convolutional neural networks, offer promising solutions in this regard. Methodology: Fifteen studies meeting the inclusion criteria were examined. The PRISMA criteria guided the exploration of cervical cancer screening studies employing AI, ML, and deep learning on PubMed/MEDLINE and Google Scholar. The search focused on "artificial intelligence" and "Pap smear." The investigation specifically delves into English-language studies post-2019 that pertain to the machine learning and deep learning classification of cervical cancer using mobile devices. Histology, animal research, and pre-2019 investigations are excluded. Titles and abstracts were carefully reviewed for any discrepancies and subsequently discussed. The process of data extraction involved compiling information from the selected articles. Result: The systematic review investigates the impact of AI and ML on cervical cancer detection, screening, and diagnosis. Our review reveals enhanced accuracy and efficiency in innovative technologies such as CytoBrain and computer-aided diagnostic systems employing Compact VGG and ResNet101. ML techniques like logistic regression, MLP, SVM, KNN, and naive Bayes prove beneficial for managing complex datasets, particularly when combined with class-balancing procedures. The promising aspects include the application of deep learning for automation and AI-assisted digital microscopy. These findings signify a transformative shift in cervical cancer screening, underscoring the potential of ML and AI technologies to elevate diagnostic accuracy and accessibility. Conclusion: Our study demonstrates advancements in both accuracy and responsiveness. Despite recognizing scientific and ethical considerations, the study underscores the potential of AI to enhance cervical cancer care. This systematic review advocates for policymakers and healthcare practitioners to use ongoing research for informed decision-making in this rapidly evolving field.

EE271 Economic Evaluation (EE) of Cervical Cancer Screening Methods in Unites States: A Systematic Literature Review

Guidelines recommend cytology screening of cervical cancer every 3-years starting at the age 21 to 29 years. For age 30 onwards primary human papillomavirus (HPV) testing or co-testing (HPV + cytology) is also recommended every 5-years through age 65. The objective of the current review is to summarise the model-based cervical cancer screening studies.

Abstract 19: Expanding Cervical Cancer Screening in Mozambique: Challenges Associated With Diagnosing and Treating Cervical Cancer

Abstract Purpose: Cervical cancer remains the most frequently diagnosed cancer among Mozambican women. Treatment options are limited as there is only one radiation machine for the population of 31 million. The MULHER cervical cancer screening study was implemented in January 2020 in Maputo, Mozambique to increase screening and detection of women with cervical cancer. We seek to describe the challenges and barriers associated with providing cancer care to this cohort. Methods: As part of the MULHER study, women ages 30-49 were prospectively enrolled and offered screening with primary human papillomavirus testing (HPV) testing followed by treatment, as appropriate, with ablation or excision for screen-positive women. Women with suspicion for cancer were referred to gynecologic oncologists who were previously trained as part of the International Gynecologic Cancer Society (IGCS) Global Curriculum and Mentorship Program. To date, three Mozambican fellows have graduated and are providing care in Maputo, with three fellows currently in training. Results: Between January 2020 and December 2022, 9,089 women underwent cervical cancer screening and 30 women were diagnosed with cancer. The mean time from biopsy to pathology report was 1.1 month (range 0.5-8.5 months) and the mean time from biopsy to first treatment was 7.7 months (range 1.9-22.7 months). In this cohort, four patients (13.3%) had early stage disease, 18 (60.0%) had locally advanced disease, 1 (3.3%) had distant metastatic disease, and seven (23.3%) were either unstaged or staging information was missing. Six patients (20.0%) died without treatment and seven patients (23.3%) are still awaiting treatment. No patients received chemoradiation, with those patients who received radiotherapy first receiving 9-12 cycles of chemotherapy due to long wait times for radiation. Conclusion: As cervical cancer screening programs are scaled up in low-resource settings, there will likely be an increase in the number of women diagnosed with cancer. Our review of this cohort shows that there are significant barriers to cancer care, even in a research cohort. These must therefore be addressed and include lack of accurate charting, lack of access to pathology and radiotherapy, and lack of a prioritization system within radiotherapy infrastructures to first address patients with potentially curative disease. Citation Format: Samantha Batman, Ricardina Rangeiro, Ellen Baker, Elaine Monteiro, Carla Carrilho, Dercia Changule, Siro Daud, Nafissa Osman, Andrea Neves, Hira Atif, Celda De Jesus, Arlete Mariano, Renato Moretti-Marques, Marcelo Vieira, Georgia Fontes-Cintra, Andre Lopes, Jean Claude Batware, Elvira Luis, Cesaltina Lorenzoni, Kathleen Schmeler, Mila Salcedo. Expanding Cervical Cancer Screening in Mozambique: Challenges Associated With Diagnosing and Treating Cervical Cancer [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 19.

Abstract LB107: A precision DNA methylation test to triage HPV positive women before referral to colposcopy-driven biopsies or ablative treatment in cervical cancer screening clinics worldwide

Abstract Cervical cancer is one of the most common cancers in women. Despite progress in prevention through Human Papilloma Virus (HPV) vaccination and success in early detection of cervical cancer through cytologic screening and HPV detection, there remains an unequal cervical cancer burden in low-resource settings, both in developed and developing countries. We have previously shown that the CervicalMethDx test can provide a Cervical Intraepithelial Neoplasia (CIN) grade 2-3 risk score, by assessing DNA methylation in a panel of three human genes (ZNF516, FKBP6 and INTS1) in samples from the United States (US), Puerto Rico, and Chile. We now tested the performance of the CervicalMethDx test on HPV-positive CIN2 and CIN3 cases (n=113) from Honduras collected from participants in the ESTAMPA clinical trial (NCT01881659). ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) is a multicentric study of cervical cancer screening with HPV testing and assessment of triage methods in Latin America, which has accrued close to 50,000 participants from twelve recruitment centers in nine Latin American countries since 2013. We hypothesized that the CervicalMethDx test can identify HPV positive women most likely to be diagnosed with CIN grades 2 and 3 by anatomic pathologists, before they are referred to colposcopy-driven biopsies. We assessed DNA methylation by quantitative Real Time Methylation Specific PCR (qMSP) analysis of sodium bisulfite-modified genomic DNA. Primers and probes were previously designed to specifically amplify the promoters of the 3 genes of interest and the promoter of a reference gene, β-actin, to assess DNA input. We performed blinded retrospective studies on well-characterized clinical samples in PreservCyt sample transport media (ThinPrep, Hologic), comparing DNA methylation levels in samples from Honduras and 88 HPV-positive previously tested US samples with No Intraepithelial Lesions or Malignancy (NILM), as controls. Our results showed that the CervicalMethDx test can correctly classify 96% of CIN2 (n=62) samples with 92% Sensitivity, 98% Specificity, and an AUC of 0.96 as well as 97% of CIN3 (n=51) samples with 96% Sensitivity, 98% Specificity, and an AUC of 0.97. Moreover, the assay correctly classified 96% of CIN2-CIN3 samples combined (n=113) with 95% Sensitivity, 98% Specificity, and AUC of 0.97, when compared to samples with NILM (n=88). Our results suggest that the CervicalMethDx test is a new and valuable tool to stratify HPV positive women prior to colposcopy-driven biopsies in developed countries and ablative treatment in developing countries, most of which are unnecessary. These results warrant further evaluation of the CervicalMethDX test in prospective, population-based studies, assessing the use of precision DNA methylation algorithms to triage HPV positive women before referral to colposcopy-driven biopsies or ablative treatments in cervical cancer screening clinics world-wide. Citation Format: Laura Palmieri, Fernando Zamuner, Yessy Cabrera, Jafet Ortiz-Quintero, Dieila Giomo De Lima, Ana Purcell-Wiltz, Amanda García-Negrón, Ashley Ramos-López, Mariana Brait, David Sidransky, Annabelle Ferrera, Rafael E. Guerrero-Preston. A precision DNA methylation test to triage HPV positive women before referral to colposcopy-driven biopsies or ablative treatment in cervical cancer screening clinics worldwide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB107.

Implementing HPV testing in 9 Latin American countries: The laboratory perspective as observed in the ESTAMPA study.

Replacement of cytology screening with HPV testing is recommended and essential for cervical cancer elimination. HPV testing for primary screening was implemented in 12 laboratories within 9 Latin American countries, as part of the ESTAMPA cervical cancer screening study. Our observations provide information on critical operational aspects for HPV testing implementation in diverse resource settings. We describe the implementation process of HPV testing in ESTAMPA, focusing on laboratory aspects. We assess the readiness of 12 laboratories to start HPV testing and their continuity capacity to maintain good quality HPV testing until end of recruitment or up to December 2021. Readiness was based on a checklist. Information from the study database; regular meetings and monitoring visits; and a questionnaire on laboratory operational aspects sent in May 2020 were used to assess continuity capacity. Compliance with seven basic requirements (readiness) and eight continuity requirements (continuity capacity) was scored (1 = compliant, 0 = not compliant) and totaled to classify readiness and continuity capacity as very limited, limited, moderate or high. Experiences, challenges, and enablers of the implementation process are also described. Seven of 12 laboratories had high readiness, three moderate readiness, and of two laboratories new to HPV testing, one had limited readiness and the other very limited readiness. Two of seven laboratories with high readiness also showed high continuity capacity, one moderate continuity capacity, and the other four showed limited continuity capacity since they could not maintain good quality HPV testing over time. Among three laboratories with moderate readiness, one kept moderate continuity capacity and two reached high continuity capacity. The two laboratories new to HPV testing achieved high continuity capacity. Based on gained expertise, five laboratories have become part of national screening programs. High readiness of laboratories is an essential part of effective implementation of HPV testing. However, high readiness is insufficient to guarantee HPV testing high continuity capacity, for which a "culture of quality" should be established with regular training, robust monitoring and quality assurance systems tailored to local context. All efforts to strengthen HPV laboratories are valuable and crucial to guarantee effective implementation of HPV-based cervical screening.

A pilot study of risk-stratified cervical cancer screening.

Background: Cervical screening programs target entire populations, although it is well established that cervical cancer risks can vary >100-fold based, in particular, on the woman's screening history. Since cervical screening switched to Human Papillomavirus (HPV) testing as the primary screening method, the risk differences are even larger as different HPV types may vary in associated cancer risk by 100 times. Furthermore, HPV infections with the most oncogenic types are declining dramatically because of HPV vaccination programs. Tailoring screening intensity based on the known cancer risk of the individual (risk-stratified screening) therefore has great potential to increase both the sensitivity and specificity. Within Horizon 2020 a major project for Risk-stratified Screening for Cervical Cancer (RISCC) has therefore been launched. We performed a pilot study of risk-stratified screening to evaluate feasibility and acceptability of offering vaginal HPV self-sampling tests to women with a higher risk of cervical cancer. Methods: We identified resident women who had had either i) atypical glandular cells in screening tests during the past six years (risk >150/100,000 woman-years) or ii) abnormal screening findings above the age of 50, but without sufficient follow-up (risk >65/100,000). The women were invited, either by short message service (SMS) or physical letters, to order an HPV self-sampling kit via the study web-platform. The returned self-collected samples were tested for HPV. If positive, women were invited for clinical follow-up. Results: Among 920 targeted women, 191 (21%) placed an order and 163 (18%) returned a self-collected sample. Among all tested samples, 19 (12%) were positive for hrHPV and 18 of these women attended clinical follow-up. Conclusions:SMS invitations to high-risk women complemented with physical letters are feasible and result in substantial requests for kits and submission of samples. Future work will focus on improving the efficiency of the procedure and further increasing attendance.

Verification of the association of the cycle threshold (Ct) values from HPV testing on Cobas4800 with the histologic grades of cervical lesions using data from two population-based cervical cancer screening trials

ObjectiveTo verify the association of high-risk human papillomavirus (hrHPV) viral load reflected by cycle threshold (Ct) values from HPV testing on Cobas4800 assay with the histologic grades of cervical lesions via analysis on the combined data from two cervical cancer screening trials and to explore the referability of Ct values in management of the abnormalities from cervical cancer primary screening.MethodsWe analyzed the data from Chinese Multi-Center Screening Trial (CHMUST) and BUJI Cervical Cancer Screening Study Project (BUJI Study). All data to be analyzed in this paper were related to provider-collected samples. One-way ANOVA was performed to compare the Ct values among different histological groups, and Kendall’s tau-b correlation was applied to examine the association between Ct values and cervical lesion grades. The stepwise incidence of CIN2+ and CIN3+ in every 100 HPV positive individuals were calculated according to the descending of the genotype specific Ct values. The highest Ct values related to CIN3+ incidence rate 4% (or 25%) were used as the cutoffs to distinguish low-Ct value cases from the high-Ct value ones.ResultsA total of 1376 women in CHUMUST and BUJI Study who were aged 30–59 and positive of hrHPV for provider-collected samples on Cobas4800 with complete data in terms of the relevant Ct values (CtV) and the histological diagnosis were included for analysis. Our data showed significant difference among different histological grades of cervical lesions in the CtV of hrHPV, HPV16-plus (positive of HPV16 only or HPV16 plus 18 and/or pooled 12-HPV), and pooled 12-HPV (P < 0.05). No significant difference was found among different grades of lesions in term of correlated CtV of HPV18-plus (positive of HPV18 only or HPV18 plus pooled 12-HPV) (P > 0.05). The CIN2+ or CIN3+ incidence per 100 positives significantly increased corresponding to the descending of the CtV of hrHPV, HPV16-plus and pooled 12-HPV. Compared with high-CtV groups (CtV > 33.2 for hrHPV, CtV > 29.6 for pooled 12-HPV), the relevant risks (RRs) of CIN2+ for hrHPV and pooled 12-HPV positive groups with low-CtV (CtV ≤ 33.2 and ≤ 29.6, respectively) were 3.2 (95%CI 2.18–4.80) and 2.3 (95%CI 1.50–3.45). Similarly, the RRs of CIN3+ for hrHPV and pooled 12-HPV positive groups with low-CtV were 6.5 (95%CI 2.83–14.80) and 2.7 (95%CI 1.15–6.39), respectively. The RRs of CIN2+ for medium- (30.3 < CtV ≤ 37.4) and low- (≤ 30.3) CtV HPV16-plus positives were 5.1 (95%CI 0.68–38.38) and 20.6 (95%CI 2.96–143.92) related to high-CtV (> 37.4) groups, and the CIN3+ incidence in low-CtV value group was nine-fold higher of that in medium-CtV ones [RRs, 9.0 (95%CI 2.89–28.10)]. In comparing with the algorithms of “HPV16-plus/18-plus + cytology ≥ ASCUS for pooled 12-HPV”, triage algorithm “HPV16-plus/18-plus + Ct value ≤ 33.2 for pooled 12-HPV” could achieve a comparable sensitivity of 93.2%.ConclusionHPV viral loads reflected by Ct values for hrHPV, HPV16-plus and pooled 12-HPV from Cobas4800 HPV testing were directly associated with the severity of cervical lesions. A lower HPV genotype-specific Ct value prompted a significantly high CIN3+ risk of 4% or higher in women positive of hrHPV, HPV16-plus or pooled 12-HPV, indicating that HPV viral load reflected by Ct values on Cobas4800 may be a promising risk indicator in management of abnormalities from primary cervical cancer screening.

HPV testing for cervical cancer screening in Mozambique: challenges and recommendations

Background Cervical cancer is the fourth most common cancer affecting women worldwide and is the leading cause of cancer and related deaths among women in Mozambique. The World Health Organization (WHO) recommends screening with human papillomavirus (HPV) testing, but it has not yet been implemented in many low- and middle-income countries (LMICs). We conducted a cervical cancer screening study in Mozambique using the careHPV test (QIAGEN, Germantown, MD, USA). This study aimed to describe our experience with HPV testing for cervical cancer screening in Maputo, Mozambique, including challenges and lessons learned. Methods We conducted a cervical cancer screening pilot demonstration project at the General Hospital of Mavalane in Maputo, Mozambique, from April 2018 to September 2019, using primary HPV testing with careHPV. We performed the direct observations and discussions with participating laboratory experts, technicians, nurses and physicians from Mozambique, Brazil and the United States. Results HPV testing was successfully implemented. The main challenges we experienced were inadequately equipped laboratory facilities, a lack of laboratory and clinical staff expertise, and difficulties procuring equipment, tests and laboratory supplies. These challenges were overcome by increasing the budget to better equip the laboratory, building relationships with procurement and importation specialists and training sessions for laboratory personnel and medical providers. Conclusions Our findings suggest that primary HPV testing is achievable in Mozambique. Several challenges were identified and are being addressed for a successful scale-up.

A pilot study of risk-stratified cervical cancer screening

Background: Cervical screening programs target entire populations, although it is well established that cervical cancer risks can vary &gt;100-fold based, in particular, on the woman’s screening history. Since cervical screening switched to Human Papillomavirus (HPV) testing as the primary screening method, the risk differences are even larger as different HPV types may vary in associated cancer risk by 100 times. Furthermore, HPV infections with the most oncogenic types are declining dramatically because of HPV vaccination programs. Tailoring screening intensity based on the known cancer risk of the individual (risk-stratified screening) therefore has great potential to increase both the sensitivity and specificity. Within Horizon 2020 a major project for RIsk-stratified Screening for Cervical Cancer (RISCC) has therefore been launched. We performed a pilot study of risk-stratified screening to evaluate feasibility and acceptability of offering vaginal HPV self-sampling tests to women with a higher risk of cervical cancer. Methods: We identified resident women who had had either i) atypical glandular cells in screening tests during the past six years (risk &gt;150/100,000 woman-years) or ii) abnormal screening findings above the age of 50, but without sufficient follow-up (risk &gt;65/100,000). The women were invited, either by short message service (SMS) or physical letters, to order an HPV self-sampling kit via the study web-platform. The returned self-collected samples were tested for HPV. If positive, women were invited for clinical follow-up. Results: Among 920 targeted women, 191 (21%) placed an order and 163 (18%) returned a self-collected sample. Among all tested samples, 19 (12%) were positive for hrHPV and 18 of these women attended clinical follow-up. Conclusions: We found that SMS invitations to high-risk women are feasible and result in substantial requests for kits and submission of samples. Future work will focus on improving the efficiency of the procedure and further increasing attendance.

Seizing the Means of Reproduction? Canada, Cancer Screening, and the Colonial History of the Cytopipette.

In recent years, self-sampling has emerged as a compelling way of increasing cervical cancer screening rates within First Nations, Inuit and Métis communities. By allowing women to take their own samples in private, when and where they are most comfortable, home testing kits have been framed as a new, unequivocally feminist technology, and a panacea in Indigenous health. But are these techniques really as ethical and empowering as they have been made out to be? To answer this question, this article traces the history of the uptake and use of cervical cancer screening technologies in Canada. By tracing the mechanics and motivations of two state-sponsored cervical cancer screening studies carried out by Canada's Department of Indian Health Services during the mid to late twentieth century, this piece explores the settler-colonial roots of cancer surveillance, and shows how the implementation of both Pap-testing and DIY forms of screening within Indigenous communities has, at least historically, been more about enacting biopolitical regimes than promoting feminist ideals or improving health outcomes.

Type-specific persistence, clearance and incidence of high-risk HPV among screen-positive Rwandan women living with HIV

BackgroundPersistent infection with high-risk human papillomavirus (hrHPV) is a critical step in cervical carcinogenesis. We report on type-specific hrHPV persistence, clearance and incidence among screen-positive Rwandan women living with HIV (WLWH).MethodsThis was a nested analysis from a large cervical cancer screening study of ~ 5000 Rwandan WLWH. Women who tested positive for hrHPV and/or visual inspection with acetic acid were referred to colposcopy. For a subset of women (n = 298) who were ≥ 6 months delayed in receiving colposcopy, we tested their screening and colposcopy visit specimens using the AmpFire HPV genotyping assay that tests 14 hrHPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) individually.ResultsThe mean, median (interquartile range [IQR]) and range of time between the screening and colposcopy visits were 644, 650 (490–820.5) and 197–1161 days, respectively. Mean, median (IQR) and range of age at the screening visit were 38, 37 (34–43) and 30–54 years, respectively. Two-hundred eighty-three (95.0%) had CD4 count (cells per mm3) data available at baseline with mean, median (IQR) and range of 592, 513 (346–717) and 0–7290, respectively. Two-hundred thirty-five WLWH were positive for at least one hrHPV type at the screening visit, of whom 50.2% had at least one HPV type-specific infection persist; 37.2% of all HPV infections detected at the screening visit persisted. Compared to all other HPV types in aggregate, HPV16 (vs. non-HPV16 types) (47.7%, p = 0.03) and HPV33 (vs. non-HPV33 types) (56.7%, p = 0.03) were significantly more likely, and HPV39 (vs. non-HPV39 types) (6.7%, p = 0.01), HPV51 (vs. non-HPV51 types) (15.6%, p < 0.01), and HPV66 (vs. non-HPV66 types (17.9%, p = 0.04) were significantly less likely, to persist. Lower CD4 counts were associated with having any persistent hrHPV infection (ptrend = 0.04) and multiple persistent hrHPV infections (ptrend = 0.04).ConclusionThere is a significant proportion of WLWH with persistent hrHPV infection, emphasizing the need to vaccinate them against HPV prior to becoming sexually active.

Why Does Cancer Screening Persist Despite the Potential to Harm?

Population screening for early-stage cancer or cancer precursors began in the mid-twentieth century, with the goal of reducing suffering from cancer illness and lengthening average life by preventing cancer deaths. Since the establishment of cancer screening, concerns have emerged that it may be doing considerable harm; despite this, screening practices have remained relatively intractable. This intractability in the face of harm is the central problematic of my analysis. I reinterpret a large study of breast, cervical and prostate cancer screening completed recently by our Australian research group, working across empirical bioethics, public health and social science. I suggest three reasons why cancer screening might persist as it does, and thus reach conclusions about what might be required to make cancer screening systems more responsive to the potential for harm.

Adjunctive testing by cytology, p16/Ki-67 dual-stained cytology or HPV16/18 E6 oncoprotein for the management of HPV16/18 screen-positive women.

High-risk human papillomavirus type 16/18 (HPV16/18) genotyping is unable to accurately discriminate nonprogressive infections from those that will progress to cervical cancer. Our study aimed to assesses if additional testing either with liquid-based cytology (LBC) or the putative progression markers p16/Ki-67 and HPV16/18 E6 oncoprotein (E6) can improve the efficiency of HPV16/18 genotyping for triaging high-risk HPV (hrHPV)-positive women through better cancer risk stratification. Women attending colposcopy after positive HPV16/18 genotyping results within the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA) hrHPV-based screening study in Tlaxcala, Mexico, underwent further testing with LBC, p16/Ki-67 dual-stained (DS) cytology and E6. We calculated measures of test performance for detecting histologically confirmed cervical intraepithelial neoplasia grade 2 or higher (CIN2+) and grade 3 or higher (CIN3+). A number of 475 (64.3%) of 739 HPV16/18-positive women had complete results for all tests. Triage positivity rates were 14.1%, 18.5% and 24.4%, for LBC, E6 and DS, respectively. Compared with LBC, DS had higher sensitivity (24.4% vs 60.0%) although lower specificity (87.0% vs 79.3%) for CIN3+ (P < .001), whereas E6 had a sensitivity of 37.8% and a specificity of 83.5%. No invasive cancer was missed by DS or E6, but 75% were in normal cytology. DS test was associated with nearly 75% reduction of colposcopy referrals compared with the direct referral of all HPV16/18-positive women, giving the least number of colposcopies (n = 4.3) per CIN3+ detected. We show that adjunctive testing of HPV16/18-positive women with DS may greatly reduce unnecessary colposcopy referrals within HPV-based screening employing HPV16/18 genotyping while retaining acceptable sensitivity for CIN2+ and CIN3+.

Abstract PO-252: Exploratory study of cervical cancer screening among Latinas in a remote agricultural community

Abstract Background: Cancer is the leading cause of death among Latinos. Compared to non- Hispanic Whites, Latinos are more likely to be diagnosed with advanced stages of disease and to experience poorer outcomes and quality of life after a cancer diagnosis. Latino women (Latinas) have among the highest cervical cancer incidence rates. Overall, the cervical cancer incidence rate among US Latinas is about 44% higher than among non-Hispanic Whites. Low rates of screening and poor adherence to recommended follow-up after an abnormal test are thought to contribute to the higher cervical cancer mortality rates among Latinas. The lack of timely cancer screening negates the benefits otherwise afforded by early detection of cancer. Limitations in the research contributes to our lack of understanding of the potential web of factors that likely influences cervical cancer screening in Latinas. Purpose: This study aimed to identify and describe potential modifiable factors in the participants that would explain the lack of cervical cancer screening utilization. Methods: In this exploratory study, we recruited Latinas in Monterey County who received primary care in a local community clinic from January 2014 to December 2018. We conducted 7 in-depth interviews to identify the stages of change, health behaviors, health beliefs, perceptions of cancer risk, and self-efficacy to complete recommended cancer screening. All interviews were conducted in Spanish and were audio-recorded. The transcripts were translated from Spanish to English for analysis. Preliminary Findings: The mean age of participants was 52.0 years (SD, 13.7; range, 29-63 years) and all were of Mexican origin. The predictors of cancer screening were identified through the analysis of the transcripts. The lack of income to see a doctor, lack of insurance, lack of knowledge about cancer prevention and risk, and the absence of primary care utilization in their native country, created barriers to cervical cancer screening. Healthy foodways, positive outlook on life, and attending Women, Infant, and Children (WIC) classes facilitated cancer screening use. Religion and cultural factors expressed as “male machismo”, as well as the use of home remedies, and having family support mediated cancer screening behaviors. Conclusion: This exploratory study informs the direction for future intervention research that ultimately can increase community knowledge of the benefits afforded by cancer early detection and timely treatment. Such interventions may result in an increase in cervical cancer screening rates in Latinas. Citation Format: Meng-Han Tsai, Daramola N. Cabral. Exploratory study of cervical cancer screening among Latinas in a remote agricultural community [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-252.

Abstract LB-165: Risk factor prediction models for triage of HR-HPV positive women: The Estampa study

Abstract Background: Cervical cancer remains an important public health problem worldwide, being the 4th most common cancer in women globally. HPV testing has been proposed for primary cervical cancer screening, given its higher sensitivity compared to cytology to detect cervical cancer precursors. However, HPV testing may lead to costly and unnecessary increases in follow-ups and/or treatments for transiently HPV positive women. Thus, triage methods are needed for HR-HPV positive women to determine optimal management. This study aims to construct and validate a risk prediction model for cervical pre-cancer based on demographics, clinical, and lifestyle characteristics among HR-HPV positive women. Methods: This analysis from the Multicentric study of cervical cancer screening and triage with HPV testing (ESTAMPA) included HR-HPV positive women aged 30-65 recruited on nine countries in Latin America from 2012 to 2019 (n=4565). The outcomes were: (1) cervical intraepithelial neoplasia grade 2 or more severe disease (CIN2+), and (2) CIN grade 3 or more severe disease (CIN3+) before final pathology review. Covariates included demographic characteristics and cervical cancer risk factors. Univariate logistic regression models were used to assess potential predictors of CIN2+ and CIN3+, controlling for the effect of the country of residence, using a multilevel approach. A multivariate logistic regression model was used to predict outcomes. After computing the probability of CIN2+ and CIN3+ among participants, we categorized these probabilities in deciles, to set the scale boundaries. Receiver-operating curves (ROC) and the Area under the Curves (AUC) were constructed. Sensitivity, specificity and predictive values were used to summarize the performance of the scoring system. Results: The prevalence of CIN2+ and CIN3+ in the study population were 14.7% and 9.7%, respectively. Age at recruitment, history of last Pap test, number of pregnancies, use of oral contraceptives, cigarette use and age at first sexual intercourse were significantly associated (p&amp;lt;0.05) with having CIN2+ and CIN3+. The AUC for the risk factor prediction model was 0.66 for CIN2+ and 0.69 for CIN3+. The optimal cutpoint selected by the Youden's statistic was the 5th decile for CIN2+ and 6th decile for CIN3+. This optimal point was for women with probabilities of CIN2+ greater than 13% and greater than 10% for CIN3+. Thus, in these deciles the number of referrals to colposcopy decreased from 100% to 60% for CIN2+ (100% to 49% for CIN3+), and the sensitivity and specificity obtained in this decile was 80% and 43% for CIN2+, respectively (73% and 54% for CIN3+). Conclusions: Our risk prediction model demonstrated a close to acceptable discrimination. This risk prediction model has the potential to reduce the number of HR-HPV positive women who are referred to colposcopy or treatment unnecessarily, reducing the burden for the patient and the healthcare system. Further analyses after pathology review are underway. Citation Format: Marievelisse Soto-Salgado, Maribel Almonte, Ana Patricia Ortiz, Erick L. Suarez, Luis R. Pericchi, Armando Baena, Rolando Herrero. Risk factor prediction models for triage of HR-HPV positive women: The Estampa study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-165.

Benefit of double-reading cytology smears as a triage strategy among high-risk human papillomavirus-positive women in Mexico.

The goal of this study was to determine whether the detection of histologically confirmed cases of cervical high-grade squamous intraepithelial lesions or worse (HSIL+) can be increased by having each liquid-based cytology (LBC) slide read by 2 cytotechnologists as part of routine screening. Over 36,212 women aged 30 to 64years participated in the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA) Study in Mexico between 2013 and 2016. For each participant, 2 cervical samples were collected at the same clinic visit, one to test for high-risk human papillomavirus (hrHPV) and the other for LBC, which was used to triage those with a hrHPV positive result. LBC slides were evaluated by 7 cytotechnologists, with each slide read independently by 2 blinded cytotechnologists. All women with atypical cells of undetermined significance or a worse result were referred to colposcopy for further evaluation and diagnosis. Three pathologists evaluated the biopsy specimens to confirm the final HSIL+ diagnosis. The HSIL+ detection rates for the single versus double reading were estimated and compared. A total of 3,914 women with a positive hrHPV result were triaged with LBC. The first and second cytology readings resulted in 43 HSIL+ cases detected; the double-reading strategy detected 9 additional HSIL+ cases, resulting in a total of 52 HSIL+ cases. The HSIL+ detection rate increased from 10.99/1000 with a single reading to 13.29/1000 with the double-reading strategy (P=.004). A 20.9% increase in HSIL+ cases detected was achieved with a double reading of the LBC slides in this sample of hrHPV-positive women.

Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America: the ESTAMPA screening study protocol

IntroductionHuman papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents...

Value of multi-quadrants biopsy: Pooled analysis of 11 population-based cervical cancer screening studies.

ObjectiveThe accuracy of colposcopy-guided biopsy is key to the success of colposcopic triage in cervical cancer screening programs. However, there is no widely adopted biopsy guideline up to date. Our study aimed to determine whether multi-quadrants biopsy improves the yield of cervical lesions.MethodsEleven population-based cervical cancer screening studies were conducted in China. Cytology, high-risk human papillomavirus (hrHPV) testing and visual inspection were performed for primary screening. Females positive on one or more tests were referred for colposcopy and biopsy. The proportion of detected cervical intraepithelial neoplasia (CIN)2+ and yields by quadrant lesion-targeted biopsy or 4-quadrant random biopsy were compared.ResultsAmong 4,923 females included, 1,606 had quadrant lesion-targeted biopsy, and 3,317 had 4-quadrant random biopsy. The cumulative CIN2+ yield increased from 0.10 for only one quadrant-targeted biopsy to 0.21, 0.34, and 0.58 for at most two, three and four quadrants targeted biopsies. Among hrHPV positive females with high-grade squamous intraepithelial lesion (HSIL)+ cytology, the cumulative CIN2+ yield of a second targeted biopsy in another quadrant was significantly increased (P<0.05). Among hrHPV-negative females, the yield of 4-quadrant random biopsies was 0.005, and the yield by lesion-targeted biopsies was 0.017. For hrHPV positive females who had 4-quadrant random biopsy, the additional CIN2+ yield for HSIL+, low-grade squamous intraepithelial lesion (LSIL) cytology, or abnormal visual inspection via acetic acid and Lugol’s iodine (VIA/VILI) were 0.46, 0.11, 0.14.ConclusionsA 4-quadrant random biopsy is recommended only for hrHPV positive females with HSIL cytology, and is acceptable if hrHPV positive with LSIL cytology or with abnormal VIA/VILI. Our findings add evidences for an objective and practical biopsy standard to guide colposcopy in cervical cancer screening programs in low- and middle-income countries.

Diagnostic Yield and Performance of a Large Population-Based Cervical Cancer Screening Program in High-Risk Rural China.

Primary cervical cancer screening by liquid-based cytology alone or with adjunctive HPV testing are available worldwide. However, little if any information is available about cervical cancer diagnostic yield of population-based cervical cancer screening in China. In response to it, we conducted a large prospective study on 40,000 women cervical cancer screening within six-month period in rural Shanxi Province, where has been reported as the highest cervical cancer rates in China. A standard cross-sectional survey by self-completed questionnaire was collected and followed by the liquid-based cytology screening. Follow-up biopsy with the diagnosis of cervical intraepithelial neoplasia 2 or higher lesion (CIN2+) were analyzed. Of initial 40,000 women participating in this study, 6.76% (2702/40,000) women had ASC-US or higher cytology screening results with ASC/SIL ratio at 6.14 (2381:388). Among them, 1.96% (782/40,000) women were found CIN lesions (95% CI, 1.68-2.23%) on confirmatory biopsies, including 0.55% (218/40,000) CIN2+ and 19 SCCa (47.5/100,000, 95% CI, 29-74/100,000). Women in Yangqu County had lower ASC/SIL ratio, but higher CIN2+ detection rate in comparison with that of Jiexiu County (6.69 vs. 8.84 and 56.7% vs. 43.9%), which reflects the cervical cancer distribution in different populations and regions. Analysis in age-stratified cytology results indicated women aged 60-65 years had the highest incidence of cytologic abnormality among all the age group; likewise, women aged >50 years were at higher risk in developing cervical high grade dysplasia or cancer than women aged <50 years (0.82% vs. 0.49%). This large-scale cervical cancer screening study provided important references as the instructive for establishing the nation-wide cervical cancer screening strategy.