Cytology-based Screening Research Articles

DETECTION OF ABNORMAL CERVICAL CYTOLOGY BY LBC (LIQUID BASED CYTOLOGY)

Introduction: Cancer cervix is the fourth most common cancer among women globally. It is responsible for 7.7% of all female cancer death.It takes around 15-20 years in normal immunity patients and 5-10 years in immune-compromised patients to convert precancerous lesions of the cervix into cancer cervix. Cervical cytology plays a very important role in the early diagnosis and management of these precancerous lesions to improve prognosis.quite low Pap smear sensitivity, in the range of 50%, but as low as 20%10 has been reported by some recent meta-analysis studies. LBC was introduced in the mid-1990s as an alternative technique to process cervical smear samples for cytological evaluation.11Studies of the accuracy of liquid-based preparations reports sensitivity of 61-66% and specicity of 82- 91%. A retrospective study was done at a private clinic and pathology lab in Di Materials And Methods: strict Shivpuri (MP) from 1st October 2020to 30th November 2022 on 760 patients. Inclusion criteria:-Patients in the age group of 21-65 years with complaints of abnormal vaginal discharge, intermenstrual bleeding, ostmenopausal bleeding, post-coital bleeding, dyspareunia, foul-smelling discharge, backache, and Lower abdominal pain were included in this study. Sample was taken with Broom, and Cyto-brush from the transformation zone and endocervix and placed in liquid xative buffered methanol solution and send to the pathology lab. Results Most of the patient 42% were between 31-40 years of age group. The majority 48.42% of them were educated up to High school. Most of them 84.07%were from rural back ground, multiparous 86.05%, and married 99.73%. 25% ofwomen visited OPD with complaints of abnormal vaginal discharge followed by menstrual abnormalities in 20.79%, other complaints were, Pain abdomen 16.97%, Vulval itching12.11%, Low back pain 3.95%, Dyspareunia 3.03% and others 5.13%. (Loss of weight and appetite, STD/genital warts) .9.08% women came for routine checkup. The most common nding on per speculum examination was Cervical ectopy in 33.95% .Normal cervix was found in 26.05%. Other ndings on Per-speculum examination were, Hypertrophied cervix, Inammation, Cervical Polyp, UV Prolapse/ cystocele, Cervical Ulcer ,Cervix ushed with the vagina and Cervical growth in. 20%, 9.08%, 4.34% 4.61% 3.03% 0.13% and 0.13% respectively. Out of 760 cases, 61.05% of patients were reported as negative for intraepithelial lesion (NILM). The most common non-neoplastic cytological nding was an inammatory smear in 25.00% of cases. Various Infections were found in 6.18% of cases, and epithelial cell abnormalities were found in 3.42% of cases. The most common abnormalities were ASC-US 0.92% and ASC-H 0.92%, followed by LSIL 0.53%, HSIL 0.66%, AGUS 0.26%, and SCC 0.13%. Bacterial vaginosis 2.37% was the most common infective organism found in cytology followed by Candida albicans 1.97%, Trichomonas vaginalis 1.71%, and Herpes simplex virus 0.13%. The cytology-based screening program is still the mainstay in the earl Conclusion y diagnosis of cancer cervix. To improve diagnostic accuracy as sensitivity and specicity in the eld of cervical cytology, Liquid-based cytology (LBC) is preferred. Its advantages over conventional Pap smears include proper visualization of cellular features due to a reduction in air-drying artifacts and reduced number of unsatisfactory smears. The residual specimens from the LBC technique can be used to detect human papillomavirus DNA through immune-cytochemistry if needed. thus, LBC is recommended as a cervical cytology screening tool to achieve the WHO elimination strategy.

Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus.

Compared with women who are human immunodeficiency virus (HIV) negative, women with human immunodeficiency virus (WWH) have a higher human papillomavirus (HPV) prevalence and increased cervical cancer risk, emphasizing the need for effective cervical cancer screening in this population. The present study aimed to validate methylation markers ASCL1 and LHX8 for primary screening in a South African cohort of WWH. In this post hoc analysis within the DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) study, a South African observational multicenter cohort study, cervical scrape samples from 411 HIV-positive women were analyzed for hypermethylation of ASCL1 and LHX8 genes, HPV DNA, and cytology. Sensitivities, specificities, and positive and negative predictive values of primary methylation-based, HPV-based and cytology-based screening were calculated for the detection of cervical intraepithelial neoplasia of grade 3 or higher. Single markers ASCL1 and LHX8 resulted in a good performance for the detection of cervical intraepithelial neoplasia of grade 3 or higher, with sensitivities of 85.9% (95% confidence interval [CI], 78.2%-93.6%) and 89.7% (83.0%-96.5%), respectively, and specificities of 72.9% (67.3%-78.5%) and 75.0% (69.5%-80.5%). Combining markers ASCL1 and LHX8 resulted in a lower sensitivity compared with HPV testing (84.6% vs 93.6%, respectively; ratio, 0.90 [95% CI, .82-.99]) and a higher specificity (86.7% vs 78.3%; ratio 1.11 [1.02-1.20]) and reduced the referral rate from 46.8% to 33.4%. ASCL1/LHX8 methylation had a significantly higher sensitivity than cytology (threshold, high-grade intraepithelial squamous lesion or worse), (84.6% vs 74.0%, respectively; ratio, 1.16 [95% CI, 1.01-1.32]) and similar specificity (86.7% vs 91.0%; ratio, 0.95 [.90-1.003]). Our results validate the accuracy of ASCL1/LHX8 methylation analysis for primary screening in WWH, which offers a full-molecular alternative to cytology- or HPV-based screening, without the need for additional triage testing.

Decline of cytology-based cervical cancer screening for COVID-19: a single-center Peruvian experience.

Cervical cancer is the second most frequent malignant disease in the Peruvian female population, and the Papanicolaou test is its main screening tool. However, the COVID-19 pandemic can hinder cervical cancer screening, reducing its scope. To analyze the decline of Papanicolaou-based cervical cancer screening due to COVID-19 in a specialized hospital in Lima. We designed a retrospective study (from 2015 to 2020) on 355 029 Papanicolaou smears at the Hospital Nacional Madre Niño San Bartolomé. T-test and one-way ANOVA were used to define differences in the study period and Ljung-Box test with ARIMA (1,0,0) model to describe and forecast monthly expected Papanicolaou smears for 2020. Throughout the six years of the study, the average Papanicolaou smears was 59 171.5 ± 8898.7 per year. However, in 2020 only 16 273 (4.58%) Papanicolaou tests were performed with a monthly mean of 1356.1 ± 684.2 (95% confidence interval 149.7 to 2861.9) (p < 0.001). The forecast showed 66 960 Papanicolaou smears for 2020 and a monthly mean of 5580 ± 129.3. Actual screenings during that year were only 16 273 Papanicolaou smears, resulting in a 76.7% reduction in cervical cancer screening during the pandemic. Our results suggest a dramatic decrease in cervical cancer screening based on Papanicolaou smears during 2020 in Peru due to prevention and control measures against COVID-19.

Routine Pap smear screening in Pakistan: A current perspective.

Routine Pap smear screening in Pakistan: A current perspective.

Oral epithelial cell segmentation from fluorescent multichannel cytology images using deep learning

Background and objectivesCytology is a proven, minimally-invasive cancer screening and surveillance strategy. Given the high incidence of oral cancer globally, there is a need to develop a point-of-care, automated, cytology-based screening tool. Oral cytology image analysis has multiple challenges such as, presence of debris, blood cells, artefacts, and clustered cells, which necessitate a skilled expertise for single-cell detection of atypical cells for diagnosis. The main objective of this study is to develop a semantic segmentation model for Single Epithelial Cell (SEC) separation from fluorescent, multichannel, microscopic oral cytology images and classify the segmented images. MethodsWe have used multi-channel, fluorescent, microscopic images (number of images; n = 2730), which were stained differentially for cytoplasm and nucleus. The cytoplasmic and cell membrane markers used in the study were Mackia Amurensis Agglutinin (MAA; n: 2364) and Sambucus Nigra Agglutinin-1 (SNA-1; n: 366) with a nuclear stain DAPI. The cytology images were labelled for SECs, cluster of cells, artefacts, and blood cells. In this study, we used encoder-decoder models based on the well-established U-Net architecture, modified U-Net and ResNet-34 for multi-class segmentation. The experiments were performed with different class combinations of data to reduce imbalance. The derived MAA dataset (n: 14,706) of SEC, cluster, and artefacts/blood cells were used for developing a classification model. InceptionV3 model and a new custom Convolutional-Neural-Network (CNN) model (Artefact-Net) were trained to classify SNA-1 marker stained segmented images (n:6101). For segmentation models, Intersection Over Union (IoU) and F1 score were used as the evaluation matrices, while the classification models were evaluated using the conventional classification metrics like precision, recall and F1-Score. ResultsThe U-Net and the modified U-Net models gave the best IoU overall (0.73–0.76) as well as for SEC segmentation (079). The images segmented using the modified U-Net model were classified by Artefact-Net and Inception V3 model with F1 scores of 0.96 and 0.95 respectively. The Artefact-Net, when compared to InceptionV3, provided a better precision and F1 score in classifying clusters (Precision: 0.91 vs 0.80; F1: 0.91 vs 0.86). ConclusionThis study establishes a pipeline for SEC segmentation with the segmented component containing only single cells. The pipline will enable automated, cytology-based early detection with reduced bias.

HPV-genotyping versus conventional cervical cytology as a screening method to detect dysplastic cervical epithelial changes

The world health organization (WHO) called for coordinated global action in 2018 to eliminate cervical cancer, ensuring that every woman is screened and treated for precancerous lesions (World Health Organization. Cervical cancer: an NCD we can overcome. Geneva, 2018. http://www.who.int/director-general/speeches/detail/cervical-cancer-an-ncd-we-can-overcome.tegy). Cytology-based screening has been for decades the conventional method of screening. Ancillary techniques have been added like immunocytochemistry with P16/Ki67 and L1-Capsid, but these methods require maintenance of complex infrastructure and highly trained personnel as well as relatively short screening intervals. HPV-based screening method to detect high-risk groups is a faster and automated method, which does not need morphologically highly qualified personal with high social costs. In the study, we have focused on the distribution of cervical lesions in the age groups with concordance of detection HPV high-risk subtypes (HPV-HR) and on the safety of the screening method. In the Institute for Pathology and Cytology-Schuettorf-Leer-Germany 146.800 samples of women from the age of and above 35 years were analyzed between the beginnings of 2020 until the beginning of 2021. 63.710 cases under 35 years old were analyzed. The samples were processed for both conventional cytological techniques and for molecular detection and subtyping of HPV-HR according to the advice and measurements of BD-manufacture. In this study, we have studied the histopathological results (Table 2) after colposcopy according to the age subgroups. The histopathological results were subdivided into no dysplasia, cervical intraepithelial neoplasia I (CIN I), cervical intraepithelial neoplasia II (CIN II), cervical intraepithelial neoplasia III (CIN III), squamous cell carcinoma (Sq.c.c), adenocarcinoma in situ (AIS), endometrial carcinoma, endocervical adenocarcinoma and cases without biopsy during the colposcopy (COB). We have used the muenchener classification III (Table 3) as a subgrading system for the cytological specimens. The frequency of detecting HPV56/59/66 is higher as detecting HPV-16 and HPV18 in age groups under 35 years old, 41–50 years old and 51–60 years old. HPV16 is detected higher in age groups 35–40 years old and above 60 years. The incidence of high squamous intraepithelial lesions (CIN II and III) is 0.92% in age group 35–40 years, 0.54% in age under 35 years, 0.59% in age group 41–50 years old, 0.35% in age group 51–60 years old and 0.15% in age group above 60 years old. There is no significance (p value = 0.4060). Low grade cervical lesions (CIN I) were 0.13% (< 35 Ys), 0.35% (35–40 Ys), 0.36% (41–50 Ys), 0.25% (51–60 Ys) and 0.098% (> 60Y s), which was statistically significant (p value = 0.04,0.60). Without dysplasia 0.19% (< 35 Ys), 0.5% (35–40 Ys), 0.56% (41–50 Ys), 0.51 (51–60 Ys) and 0.26% (> 60 Ys). There is no significance between occurrence of cervical dysplasia and without dysplasia despite of detection of HPV-HR subtypes (p value = 0.1754). The only use of HPV-subtyping is not a secure method and a protective way for women. There are worldwide many HPV-positive cases, which have been psychologically impaired with higher costs, although they have no cervical epithelial changes during the HPV-infection. There are many HPV-negative cases, in some studies up to 13% of cases, which develop cervical cancer. We have the opinion and are convinced that the screening should be both morphologically via cytological examination and may be with adding immunocytochemistry to detect the really dysplastic cervical lesions. HPV-subtyping may be added every three years to detect the concomitant subtype.

Feasibility of implementing cytology-based cervical cancer screening national program in Lebanon: A pilot study.

To review our national cervical cancer screening program using existing Ministry of Public Health primary healthcare centers (PHCs) and report the impact of women's knowledge, attitude, behavior, and practices on screening uptake and outcome. A cross-sectional study on cervical cancer screening offered to sexually active Lebanese women aged 21 years and above visiting PHCs. Exclusions were history of complete hysterectomy, gynecologic cancers, and current pregnancy. Data were collected through a questionnaire and conventional cervical smear performed by trained healthcare providers and sent to one centralized cytopathology laboratory. Of 12 273 eligible women, 1.7% had an abnormal cervical smear test including 161 atypical squamous cells (ASC) of undetermined significance, 6 atypical glandular cells of undetermined significance, 16 low-grade squamous intraepithelial lesion (SIL), 17 ASC-cannot rule out high-grade SIL, 11 high-grade SIL, and one invasive carcinoma. Knowledge and attitudes significantly affected participation in screening; women lacking awareness had rarely undergone a cervical smear. In Lebanon, cytology-based cervical cancer screening is feasible within the PHCs. Positive screen incidence was low. Despite previous campaigns, a low level of knowledge persists, and affects women's com with the screening guidelines. Advocacy and awareness activities by key healthcare providers may help to improve participation.

P16/Ki-67 Dual Staining in Positive Human Papillomavirus DNA Testing for Predictive Diagnosis of Abnormal Cervical Lesions in Northeastern Thai Women.

Cervical cancer screening can effectively reduce new cervical cancer cases, including in Thailand. The abnormal results are subsequently referred for colposcopy. To avoid unnecessary colposcopy, an efficient triage is still needed for validation. This study aimed to investigate the overall positivity of cytology-based screening, HPV detection, and p16/Ki-67 dual staining and evaluate different triage strategies for predictive diagnosis of abnormal cervical lesions in northeastern Thailand. Cervical cells were collected from 191 women who came for cervical screening in the gynecological outpatient department during March 2019-February 2020. Pap smear samples were classified into 6 groups including 17 atypical glandular cells (AGC), 21 atypical squamous cells of undetermined significance (ASC-US), 7 atypical squamous cells - cannot exclude HSIL (ASC-H), 26 low-grade squamous intraepithelial lesions (LSILs), 19 high-grade SILs (HSILs) and 101 no squamous intraepithelial lesion (noSIL). Polymerase chain reaction (PCR) was performed for HPV DNA detection. HPV genotyping was determined by reverse line blot hybridization. P16/Ki-67 dual staining was performed by using CINtec PLUS Cytology kit. Biopsies from abnormal screening were collected for surgical pathology classification. High-risk HPV (HR-HPV) infection was 2.97%, 29.41%, 38.10%, 57.14%, 46.15% and 84.21% in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL cytology respectively. P16/ Ki-67 in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL was 0.99%, 5.88%, 9.52%, 42.86%, 26.92% and 63.16%, respectively (P-value < 0.001). Among p16/Ki-67 positive cases, 96.15% (25/26) were infected with HPV and 84.62% (22/26) were HR-HPV. The overall positivity of each and co-testing between cytology or HPV DNA testing or p16/Ki-67 dual staining was evaluated. In each cervical lesion, primary HPV DNA testing showed the highest sensitivity, but low specificity. The combined all HPV/HR-HPV with p16/Ki-67 detection increased the specificity of abnormal cervical lesions. P16/Ki-67 dual stain cytology in HPV-positive women performs well for diagnosis of abnormal cervical lesions and should be considered for management of HPV-positive women to avoid unnecessary colposcopy referrals.

Cervical Imaging in the Low Resource Setting: A Review.

Cervical cancer is one of the most significant global health inequities of our time and is the fourth most common cancer in women worldwide, disproportionally affecting developing countries where the disease burden is 84%. Sometimes referred to as preventable cancer, it progresses slowly, providing a window of time for routine screening in which pre-cancerous lesions can be identified and treated. The high mortality rate can be attributed to many reasons, including the high cost of cytology-based screening, lack of human resources to conduct screening, and inadequate preventive medicine services and systems. Due to its slow progression, early intervention is feasible with appropriate screening. However, the standard screening procedures require access to lab-based tests and physician expertise. Several imaging devices have been introduced in the literature to aid cervical screening in low-resource settings. This review details the instrumentation and clinical testing of devices currently deployed in low-resource locations worldwide. The devices’ imaging, portability, illumination, and power requirements (among other metrics) are documented with specifics of human pilot studies conducted with these tools.

Selected Articles from This Issue

Inflammatory and insulinemic pathways have been linked to prostate cancer; thus, health behaviors that activate these pathways may impact prostate cancer survivorship. In this study, Langlais and colleagues predicted biomarker levels of inflammation, hyperinsulinemia, and insulin resistance pathways from questionnaire data among 2,056 men with prostate cancer. The authors examined the scores in relation to risk of prostate cancer progression. Over a median of 6.4 years of follow-up, the most pro-inflammatory and pro-insulinemic behaviors following a prostate cancer diagnosis were associated with a 1.6- to 2.8-fold increased risk of prostate cancer progression. Limiting inflammation and insulin hypersecretion through diet and physical activity may improve prostate cancer survivorship.Testicular germ cell tumors (TGCTs), whose etiology is largely unknown, are believed to arise from primordial gonocytes with an altered DNA methylation reprogramming. Grasso and colleagues evaluated the association between 273 single-nucleotide polymorphisms (SNPs) from 28 DNA methylation-related genes and TGCT risk using summary statistics from the Genome Wide Association Study meta-analysis of the international Testicular Cancer Consortium on 10,156 TGCT cases and 179,683 controls. Four MTHFR SNPs, potentially affecting DNA methylation pattern, were associated with TGCT risk. This suggests that TGCT pathogenesis could be linked to folate cycle status, and this relation could be partly due to hereditary factors.In the United States (US), the incidence of Hodgkin lymphoma (HL) differs by ethnicity. In a large population-based case-control study, Graham and colleagues found that having a foreign-born mother (versus a US-born mother) was associated with an increased risk of early onset HL among non-Hispanic White individuals and a decreased risk among Hispanic individuals. In addition, sex, birthweight and parental age were also linked to risk of early onset HL. The findings suggest that the etiology of early onset HL is multi-faceted, and the observed disparity warrants further evaluation.This article describes the randomized transition from established cytology-based screening to primary HPV-based screening in Norway. This programmatic change required substantial modifications to existing infrastructure and screening protocols, affecting activity volumes, staff training, and changes in the data-flow and communication systems. Nygård and colleagues report a relative increase of 60% in the detection of cervical precancers and 40% in cancer using HPV-based screening as compared to the cytology-based screening. Introducing new screening technology gradually and in a controlled manner should be considered in both established and novel population-based cancer screening programs and specifically implementing HPV-based screening to advance the cervical cancer elimination.

A systematic review of economic evaluations of cervical cancer screening methods

ObjectiveThe aims of this systematic review were to (1) identify primary- and model-based economic evaluations of cervical cancer screening methods and to (2) provide a contextual summary of valuation outcomes associated with three types of cervical cancer screening tests: visual inspection with acetic acid, human papillomavirus deoxyribonucleic acid, and Papanicolaou smear.IntroductionCervical cancer screening is an important public health priority with the potential to improve the detection of precancerous lesions in high-risk females for early intervention and disease prevention. Test performance and cost-effectiveness differ based on the specific screening method used across different platforms. There is a need to appraise existing economic evaluations of cervical cancer screening methods.MethodsThis review considered primary-based and model-based full economic evaluations of cervical cancer screening methods. The evaluation methods of interest included cost-effectiveness analysis, cost-utility analysis, cost-minimization analysis, cost–benefit analysis, and cost-consequence analysis. We searched Scopus, PubMed, National Health Economic Evaluation Database (NH EED), Cochrane, and the Health Economic Evaluation Database for full economic evaluations of cancer screening methods. No formal date restrictions were applied. Model-based and primary-based full economic evaluations were included. A critical appraisal of included studies was performed by the main investigator, while a second independent reviewer assessed critical appraisal findings for any inconsistencies. Data were extracted using a standardised data extraction tool for economic evaluations. The ultimate outcomes of costs, effectiveness, benefits, and utilities of cervical cancer screening modalities were extracted from included studies, analysed, and summarised.ResultsFrom a total of 671 screened studies, 44 studies met the study inclusion criteria. Forty-three studies were cost-effectiveness analyses, one study reported both cost-utility and cost-effectiveness outcomes, and another study reported cost utilities of cervical cancer screening methods only. Human papillomavirus (HPV) DNA testing was reported as a dominant stand-alone screening test by 14 studies, while five studies reported visual inspection with acetic acid (VIA) as a dominant stand-alone screening test. Primary HPV screening strategies were dominant in 21 studies, while three studies reported cytology-based screening strategies as the dominant screening method.ConclusionsExisting evidence indicates that HPV-based and VIA testing strategies are cost-effective, but this is dependent on setting. Our review suggests the limited cost-effectiveness of cytology-based testing, which may be due in part to the need for specific infrastructures and human resources.Systematic review registrationPROSPERO CRD42020212454.

Do they cope or mope? A survey of GPs’ experiences with the changes in the Norwegian Cervical Cancer Screening Programme

Objective To explore Norwegian general practitioners’ (GPs) experiences with the changes in the cervical cancer screening programme and to uncover which aspects of the programme they find most challenging. Design We conducted an electronic cross-sectional survey. Setting Norwegian GPs were invited to participate in the survey between February and September in 2020. Subjects One hundred and fifty-five of 429 invited Norwegian GPs responded. Main outcome measures Self-reported measures were used to analyse GPs experiences and beliefs related to the screening programme. Results Most GPs did not find it particularly challenging to keep up with the changes in the screening programme, regardless of whether they came from areas with HPV-based or cytology-based cervical cancer screening implemented. Challenges concerning the follow-up of patients after an abnormal test were a frequently reported issue. We did not find any differences in how often GPs were uncertain of the follow-up of an abnormal test result in areas with HPV-based compared to cytology-based screening. Conclusions The implementation of HPV-based cervical cancer screening in women 34–69 years does not seem to have affected how challenging the GPs perceive the screening programme. Key Points How Norwegian general practitioners (GPs) keep up with changes in the Norwegian Cervical Cancer Screening Programme (NCCSP) has not been assessed previously. Most GPs did not find it particularly challenging to keep up with changes in the NCCSP regardless of whether they belonged to an area of HPV-based or cytology-based screening. The follow-up of patients with an abnormal test result was one of the main challenges reported by the GPs.

Cytology-based Screening for Anal Intraepithelial Neoplasia in Immunocompetent Brazilian Women with a History of High-Grade Cervical Intraepithelial Neoplasia or Cancer.

To determine the prevalence and possible variables associated with anal intraepithelial neoplasia and anal cancer in immunocompetent women with high-grade cervical intraepithelial neoplasia. A cross-sectional study involving immunocompetent women with a histological diagnosis of high-grade cervical intraepithelial neoplasia and cervical cancer, conducted between January 2016 and September 2020. All women underwent anal cytology and answered a questionnaire on characterization and potential risk factors. Women with altered cytology were submitted to anoscopy and biopsy. A total of 69 women were included in the study. Of these, 7 (10.1%) had abnormal anal cytology results: (high-grade lesion, atypical squamous cells of undetermined significance, and atypical squamous cells, cannot exclude high-grade lesions: 28,5% each; low grade lesion: 14,3%). Of the anoscopies, 3 (42.8%) showed alterations. Of the 2 (28,5% of all abnormal cytology results) biopsies performed, only 1 showed low-grade anal intraepithelial neoplasia. The average number of pregnancies, vaginal deliveries, and abortions was associated with abnormal anal cytology. However, the highest mean regarding the cesarean sections was associated with normal cytology. The prevalence of anal intraepithelial neoplasia was compatible with data from recent studies, especially those conducted in Brazil. Opportunistic screening for anal intraepithelial neoplasia in this high-risk population should be considered. Anal cytology is suitable for this purpose, due to its low cost and feasibility in public health services.

Abstract 6239: Colposcopy referral rates in an organized cytology-based cervix screening program after receipt of multiple rounds of HPV-based screening in the FOCAL trial

Abstract Purpose: Due to the increased sensitivity but reduced specificity of HPV testing compared to cytology to detect cervical lesions, a shift from cytology to HPV-based screening will initially raise population colposcopy referrals rates, which could put a strain on the healthcare system. However, it is unclear if this increase persists past the initial round of HPV screening or if rates will subsequently decrease due to earlier detection of precancer using HPV screening, which once treated may not reoccur. Methods: Participants of the HPV FOr CervicAL Cancer (FOCAL) randomized controlled trial (N = 25,223; 2008-2016) received up to two rounds of HPV-based cervix screening during the trial before returning to the cytology-based screening program in British Columbia, Canada (BC). After trial exit, participants were followed through the provincial screening program, which collects results from all screens received in BC, to detect any referral to colposcopy. A comparison cohort from the BC general screening population was created by selecting individuals who were eligible for FOCAL but not invited to participate and pulling their screening data from the provincial registry over the same time period. Post-trial colposcopy rates, calculated per-screen (not per participant), were calculated for the FOCAL population and comparison cohort overall and for those who received one round of HPV testing, those who received two rounds, those who received a negative result on their one round of testing, and those who received two negative results on their two rounds of testing. Results: The post-trial colposcopy referral rate in the overall FOCAL population was lower than in the comparison cohort. FOCAL had 180 referrals out of 30654 screens (5.9 per 1000 screens, 95%CI: 5.1-6.8), whereas the comparison cohort had 1765/177880 (9.9/1000, 95%CI: 9.5-10.4). The rates between those who had one versus two HPV tests were similar: one test: 99/17599 (5.6/1000, 95%CI: 4.6-6.8); two tests: 100/16945 (5.9/1000, 95%CI: 4.9-7.2). Rates were much lower among those who received negative results: one negative result: 55/15551 (3.5/1000, 95%CI: 2.7-4.6); two negative results: 40/12438 (3.2/1000, 95%CI: 2.4-4.4). Conclusions: After the first round of HPV-based cervix screening, colposcopy rates may decrease potentially below that seen in a cytology-based program. To avoid a surge in colposcopy referrals that could exceed health system capacity, the introduction of HPV-based screening should be done in waves, for example by inviting a new age group each year to HPV-based screening. Citation Format: Anna Gottschlich, Jennifer J. Anderson, Lovedeep Gondara, Marette Lee, Dirk van Niekerk, Laurie W. Smith, Darrel Cook, Lily Proctor, Joy Melnikow, Gavin Stuart, Ruth E. Martin, Stuart Peacock, Eduardo L. Franco, Mel Krajden, Gina Ogilvie. Colposcopy referral rates in an organized cytology-based cervix screening program after receipt of multiple rounds of HPV-based screening in the FOCAL trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6239.

Performance of Cervical Screening a Decade Following HPV Vaccination: The Costa Rica Vaccine Trial.

We investigated the impact of human papillomavirus (HPV) vaccination on the performance of cytology-based and HPV-based screening for detection of cervical precancer among women vaccinated as young adults and reaching screening age. A total of 4632 women aged 25-36 years from the Costa Rica HPV Vaccine Trial were included (2418 HPV-vaccinated as young adults and 2214 unvaccinated). We assessed the performance of cytology- and HPV-based cervical screening modalities in vaccinated and unvaccinated women to detect high-grade cervical precancers diagnosed over 4 years and the absolute risk of cumulative cervical precancers by screening results at entry. We detected 95 cervical intraepithelial neoplasia grade 3 or worse (52 in unvaccinated and 43 in vaccinated women). HPV16/18/31/33/45 was predominant (69%) among unvaccinated participants, and HPV35/52/58/39/51/56/59/66/68 predominated (65%) among vaccinated participants. Sensitivity and specificity of cervical screening approaches were comparable between women vaccinated as young adults and unvaccinated women. Colposcopy referral rates were lower in the vaccinated group for HPV-based screening modalities, but the positive predictive value was comparable between the 2 groups. Among women approaching screening ages, vaccinated as young adults, and with a history of intensive screening, the expected reduction in the positive predictive value of HPV testing, associated with dropping prevalence of HPV-associated lesions, was not observed. This is likely due to the presence of high-grade lesions associated with nonvaccine HPV types, which may be less likely to progress to cancer.

Human papillomavirus and cervical cancer: an insight highlighting pathogenesis and targeting strategies.

Cervical cancer is marked by the uncontrolled proliferation and division of cells making up the cervix. Because of its enormous population, Asia accounts for more than half of the cervical cancer cases and deaths in the world. Cervical cancer is the major cause of death from cancer in women in rural as well as urban areas in India. In most cases, persistent infection with highly infectious types of human papillomavirus (HPV) such as HPV 16 and 18 is believed to be the cause of the disease. The HPV virus is primarily reported to invade cervical epithelial cells and then goes through a non-viremic infection cycle under the influence of various potent viral oncogenic proteins, namely E6 and E7. Among several other risk factors, increased oxidative stress, hyperactivation of inflammatory pathways, and immunological factors play a key role in cervical cancer pathogenesis. Although, standardized screening services in developed countries have substantially reduced the prevalence of cervical cancer but there are numerous drawbacks to cytology-based screening. Advances in understanding the virology of the human papillomavirus have prompted the discovery of several novel biomarkers of different categories such as protein-based, DNA-based as well as stem cell-based markers. The incorporation of biomarker information will assist in recognizing efficacious therapy systems as well as improve the prognosis of cervical malignancy. The review discussed the role of HPV in the development of cervical cancer and its pathogenesis. Further, summarized the potential therapeutic biomarkers for the prevention and treatment of cervical cancer.

P16/Ki-67 Dual Staining Is a Reliable Biomarker for Risk Stratification for Patients With Borderline/Mild Cytology in Cervical Cancer Screening.

To evaluate p16/Ki-67 dual-staining performance for detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in the management of women with minor cervical abnormalities. All 759 enrolled patients were tested for cytology, high-risk human papillomavirus (HR-HPV) and dual p16/Ki-67 staining. Positivity rates for HR-HPV and dual staining increased as dysplasia was worsened from non-CIN (37.6% and 0%) to CIN1 (62.5% and 1.6%) and CIN2+ (98.7% and 97.3%), respectively. HPV18 and HPV16 exhibited the highest odds ratios (53.16 and 11.31) in the CIN2+ group. Both p16/Ki-67 dual staining and HR-HPV presented similar sensitivities (97.3% and 98.7%, respectively) for CIN2+ detection. Dual staining specificity, however, was 99.3%, significantly higher compared to HR-HPV testing (52.2%). The utility of dual staining was evaluated in different screening strategies and appeared to reduce the number of colposcopies required for the detection of CIN2+ cases. p16/Ki-67 dual-staining cytology is a surrogate triage biomarker in cytology-based screening programs, with high performance for efficient risk stratification of women with mild cervical abnormalities.

Human papillomavirus genotype distribution in low-grade squamous intraepithelial lesion cytology, and its immediate risk for high-grade cervical lesion or cancer: a single-center, cross-sectional study

ObjectiveTo investigate the distribution of human papillomavirus (HPV) genotypes in low-grade squamous intraepithelial lesion (LSIL) cytology and the immediate risk of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) lesions.MethodsThis prospective cross-sectional study enrolled women aged ≥21 years that were diagnosed with LSIL cytology at Siriraj Hospital (Bangkok, Thailand) during 2017–2019. Anyplex II HPV testing was performed to detect 14 high-risk HPV cases prior to colposcopy-directed biopsy.ResultsIn total, 318 patients were included in the final analysis. Of those, 24 (7.5%), 241 (75.8%), 53 (16.7%) were aged 21–25 years, 25–50 years, and ≥50 years, respectively. Eighty-two patients (25.8%) had abnormal screening results within the previous 5 years. High-risk HPV infection was found in 188 patients (59.1%) with 127 (39.9%) having single and 61 (19.2%) having multiple infections. The five most common HPV genotypes were HPV 66 (18.6%), HPV51 (9.7%), HPV58 (9.4%), HPV16 (9.1%), and HPV56 (8.2%). The immediate risk of CIN2+ was 6% in LSIL, regardless of the HPV status, 8% in high-risk HPV-positive LSIL, and 3.1% in high-risk HPV-negative LSIL. When using 6% as the threshold risk for colposcopy, performing reflex HPV testing in LSIL cytology can decrease the number of colposcopies by 40.9%, with an area under the receiver operating characteristic curve of 0.6 (95% confidence interval, 0.5–0.7).ConclusionThe study findings support the idea that geographic variations affect the HPV genotype. Reflex HPV testing may decrease the number of colposcopies in cytology-based screening regions with a high prevalence of low-carcinogenic HPV.

214 HPV-Based cervical screening in Portugal

Introduction and aims of the study: Portugal’s National Cervical Screening Program has changed in 2017 from cytology-based screening to HPV testing-based screening, including women aged 25 to 60 years. Samples are collected in primary care and patients are referred to Cervical Pathology Units when screened positive for high-risk HPV. Our aim was to characterize patients with high-grade lesions referred to our unit with HPV based-testing and evaluate the outcomes. Methods: A retrospective observational study was conducted concerning the period from January to October 2020 in Instituto Português de Oncologia de Coimbra.

Loss to Follow-Up and the Care Cascade for Cervical Cancer Care in Rural Guatemala: A Cross-Sectional Study.

PURPOSEMore than 80% of cervical cancer cases and deaths occur in low- and middle-income countries. Here, we analyze a large geographically extensive cross-sectional data set from the Western rural highlands of Guatemala. Our objective is to better characterize weak points in care along the cervical cancer care continuum and investigate sociodemographic and clinical correlates of loss to follow-up.METHODSWe conducted a retrospective review of electronic health records data from July 21, 2015, through December 10, 2020 for a cytology-based screening and cervical cancer treatment program. We used a care cascade analysis to characterize the progression of individuals through screening, confirmatory testing, and treatment. We examined demographic and clinical factors correlated with screening and loss to follow-up using multivariate logistic regression.RESULTSA total of 8,872 individuals were included in the analysis. Five thousand nine hundred thirteen cervical cancer screenings were conducted. 4.1% of all screening tests were abnormal, including 0.61% cervical intraepithelial neoplasia or overt cervical cancer. Care cascade analysis showed that 67% of eligible women accepted screening. Of those requiring confirmatory testing or treatment, 73% completed recommended follow-up. In adjusted multivariable analysis, prior history of sexual transmitted infection, prior experience with cervical cancer screening, older age, and current contraceptive use were associated with accepting screening. Age and contraceptive use were also associated with retention in care after a positive first screen.CONCLUSIONIn a large rural Guatemalan retrospective cohort, a care continuum analysis showed that both declining the opportunity to receive cervical cancer screening as well as declining confirmatory testing after a first positive screen were both important weak points along the care continuum. These data support the need for comprehensive and culturally appropriate initiatives to improve screening uptake and retention in care.