Performance of Nomogram Prediction Combining MiRNAs in Cervical Mucus, HPV Genotype and Age for Cervical Cancer and its Precursor Lesions

Abstract Cervical cancer is the fourth most common cancer in women worldwide. Although cytology or HPV testing is available for screening, these techniques have their drawbacks and optimal screening methods are still being developed. Here, we sought to determine whether aberrant expression of miRNAs in cervical mucus could be an ancillary test for cervical neoplasms. The presence of miRNAs in 583 and 126 patients (validation and external cohorts) was determined by real-time RT-PCR. Performance of a combination with five miRNAs (miR-126-3p, -451a -144-3p, -20b-5p and -155-5p) was estimated by ROC curve analysis. Predicted probability (PP) was estimated by nomograms comprising -ΔCt values of the miRNAs, HPV genotype and age. A combination of five miRNAs showed a maximum AUC of 0.956 (95%CI: 0.933-0.980) for discriminating cancer. Low PP scores were associated with good prognosis over the 2-year observation period (p<0.05). Accuracy for identifying cancer and cervical intraepithelial neoplasia (CIN)3+ by nomogram was 0.983 and 0.966, respectively. PP was constant with different storage conditions of materials. We conclude that nomograms using miRNAs in mucus, HPV genotype and age could be useful as ancillary screening tests for cervical neoplasia.

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Cervical Cancer Screening Programs in Europe: The Transition Towards HPV Vaccination and Population-Based HPV Testing

Viruses ◽

10.3390/v10120729 ◽

2018 ◽

Vol 10 (12) ◽

pp. 729 ◽

Cited By ~ 42

Author(s):

Andreas Chrysostomou ◽

Dora Stylianou ◽

Anastasia Constantinidou ◽

Leondios Kostrikis

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Hpv Vaccination ◽

Screening Method ◽

Population Based ◽

Screening Tests ◽

Screening Methods ◽

Hpv Testing ◽

Screening Programs

Cervical cancer is the fourth most frequently occurring cancer in women around the world and can affect them during their reproductive years. Since the development of the Papanicolaou (Pap) test, screening has been essential in identifying cervical cancer at a treatable stage. With the identification of the human papillomavirus (HPV) as the causative agent of essentially all cervical cancer cases, HPV molecular screening tests and HPV vaccines for primary prevention against the virus have been developed. Accordingly, comparative studies were designed to assess the performance of cervical cancer screening methods in order to devise the best screening strategy possible. This review critically assesses the current cervical cancer screening methods as well as the implementation of HPV vaccination in Europe. The most recent European Guidelines and recommendations for organized population-based programs with HPV testing as the primary screening method are also presented. Lastly, the current landscape of cervical cancer screening programs is assessed for both European Union member states and some associated countries, in regard to the transition towards population-based screening programs with primary HPV testing.

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A New MicroRNA Expression Signature for Cervical Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000863 ◽

2017 ◽

Vol 27 (2) ◽

pp. 339-343 ◽

Cited By ~ 13

Author(s):

Ping Sun ◽

Yong Shen ◽

Jiao-Mei Gong ◽

Li-Li Zhou ◽

Jia-He Sheng ◽

...

Keyword(s):

Cervical Cancer ◽

Intraepithelial Neoplasia ◽

Lymph Node Involvement ◽

Healthy Controls ◽

Aberrant Expression ◽

Gynecology And Obstetrics ◽

Significant Difference ◽

Node Involvement ◽

Novel Biomarkers ◽

Cancer Tissues

BackgroundCervical cancer is the second most common cancer among women worldwide. The potential of microRNAs as novel biomarkers in cervical cancer is growing.ObjectivesIn this study, we investigated the functions and targets of miR-466 in cervical cancer tissues.MethodsFresh cervical tissues were obtained from 157 patients with cervical cancer, cervical intraepithelial neoplasia (CIN), and healthy controls, and the tissues were immediately frozen in liquid nitrogen until use. The RNA was extracted and quantitative real-time polymerase chain reaction (PCR) was performed.ResultsA total of 157 participants were summarized, including 56 patients with cervical cancer, 60 patients with CIN, and 49 healthy controls. The expression levels of miR-466 in cervical cancers (0.68) were higher than that in healthy controls (0.082) (P < 0.01). The average fold changes of miR-466 in the patients with CIN group and people group were 0.28 and 0.082, respectively (P < 0.01). It was a statistically significant difference in patients with lymph node involvement (P = 0.022). However, the expression of miR-466 was not correlated with International Federation of Gynecology and Obstetrics stages, tumor size, or vascular invasion (P = 0.506, P = 0.667, and P = 0.108, respectively).ConclusionsOur results indicate that the aberrant expression of miR-466 is closely associated with the occurrence and development of cervical cancer.

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The use of micro RNA in the early detection of cervical intraepithelial neoplasia

Carcinogenesis ◽

10.1093/carcin/bgaa046 ◽

2020 ◽

Cited By ~ 1

Author(s):

Julia Wittenborn ◽

Leonore Weikert ◽

Birgit Hangarter ◽

Elmar Stickeler ◽

Jochen Maurer

Keyword(s):

Cervical Cancer ◽

Squamous Cell Carcinoma ◽

Early Detection ◽

Cell Carcinoma ◽

Cervical Intraepithelial Neoplasia ◽

Squamous Cell ◽

Intraepithelial Neoplasia ◽

Cervical Mucus ◽

Micro Rna ◽

Screening Programs

Abstract An important issue in current oncological research is prevention as well as early detection of cancer. This includes also the difficulty to predict the progression of early or pre-cancerous lesions to invasive cancer. In this context, the characterization and categorization of pre-neoplastic lesions of squamous cell carcinoma [cervical intraepithelial neoplasia (CIN)] are an important task with major clinical impact. Screening programs are worldwide established with the aim to detect and eradicate such lesions with the potential to develop untreated into cervical cancer. From the literature it is known that around 5% of CIN 2 and 12% of CIN 3 cases will progress to cancer. The use of molecular markers extracted from cervical mucus might help to identify these high-risk cases and to exclude unnecessary biopsies or surgical treatment. Here we can show that micro RNA (miRNA) analysis from cervical mucus of 49 patients allowed us to distinguish between healthy patients and patients with CIN 3. The miRNA panel used in combination allowed for highly significant testing (P < 0.0001) of CIN 3 status. In parallel, the human papillomavirus status of the patients, the most important factor for the development of cervical cancer, significantly correlated with the miRNA markers hsa-miR-26b-5p, hsa-miR-191-5p and hsa-miR-143-3p, a subpanel of the original six miRNAs. We provide here a proof-of-concept for cervical mucus-based testing for pre-neoplastic stages of cervical squamous cell carcinoma.

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Is Primary HPV with Secondary p16/Ki67 Dual-Stain an Alternative HSIL-Risk Detection Strategy in Cervical Cancer Screening for Women under 30 Years?

Diagnostics ◽

10.3390/diagnostics11112012 ◽

2021 ◽

Vol 11 (11) ◽

pp. 2012

Author(s):

Martyna Trzeszcz ◽

Maciej Mazurec ◽

Robert Jach ◽

Karolina Mazurec ◽

Zofia Jach ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Age Groups ◽

Intraepithelial Neoplasia ◽

Screening Strategy ◽

Screening Tests ◽

Cervical Intraepithelial Neoplasia Grade ◽

Predictive Values ◽

Age Range

Recently, cervical cancer rates elevation has been noted in women aged 20–39 years in regions with a very high human development index (HDI). The onset of cancer elevation rates is observed in the age range of 25–29 years, which should necessitate effective precancer screening in younger age groups, including those <25 years. From 30.066 liquid-based screening tests results (n = 30.066), 3849 liquid-based cytology, 1321 high-risk human papillomavirus (HRHPV) and 316 p16/Ki67 performed in women <30 years were selected. Performance characteristics were calculated for three screening models: primary HRHPV with p16/Ki67 triage, primary cytology with reflex HPV and primary cytology alone. Primary HRHPV with p16/Ki67 triage was significantly more sensitive in high-grade squamous intraepithelial lesion quantified with cervical intraepithelial neoplasia grade 2 or worse [HSIL(CIN2+)] detection than cytology with reflex HRHPV and cytology alone (83.3% vs. 70.8%/45.8%) and had significantly higher diagnostic predictive values (PPV:29.4%/21.3%/22.9%; NPV:91.7%/82.9%/82.2%, respectively at CIN2+ threshold). The number of colposcopies per HSIL(CIN2+) detection indices was 3.4, 4.7 and 4.4, respectively. Primary HPV testing in women <30 years with p16/Ki67 triage of HPV-positive cases might be an effective cervical cancer screening strategy for HSIL(CIN2+) detection with superior diagnostic performance when compared with primary cytology-based models. Women <25 years might also benefit from an introduction to a more sensitive screening approach.

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Prevention of cervical cancer: early detection of precancerous lesions of cervix in women from a marginalized environment

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20184984 ◽

2018 ◽

Vol 7 (12) ◽

pp. 5156

Author(s):

D. M. Christe ◽

Anjalakshi Chandrasekar ◽

K. Jayashree ◽

P. Meenalochani ◽

Shaanthy T. K. Gunasingh

Keyword(s):

Cervical Cancer ◽

Early Detection ◽

Visual Inspection ◽

Histopathological Examination ◽

Precancerous Lesions ◽

Low Cost ◽

Intraepithelial Neoplasia ◽

Cost Effective ◽

Risk Groups ◽

Screening Tests

Background: The objective of the present study was to find out the efficacy of low-cost methods, available for screening for cervical cancer and early detection of precancerous lesions, of cervix.Methods: The study with power above 80%, was conducted over a period of almost three years. Women aged below fifty years were included in the study. A total of 100 women were diagnosed with cervical intraepithelial neoplasia (CIN) and 244 women with chronic cervicitis by histopathological examination reports. Ten women were HIV positive. Results: Low cost screening tests of visual inspection of cervix after application of 5% acetic acid (VIA) and visual inspection of cervix after application of Lugol’s iodine (VILI) were positive in 75% of women with CIN and in combination with colposcopy, positive in 93%. The diagnostic accuracy of colposcopy was highest at 86%. (Odds ratio-.48.79).Conclusions: Initial screening for younger women with fewer years of exposure, the low cost tests, VIA / VILI could be used under low magnification. Colposcopy should be done for all women with positive tests. The costlier human papilloma virus (HPV) tests should be done at cost effective purpose for high risk groups and when indicated, for early detection of precancerous lesions of cervix and prevention of cervical cancer.

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Screening for non-communicable diseases

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20200881 ◽

2020 ◽

Vol 9 (3) ◽

pp. 1092

Author(s):

D. M. Christe ◽

S. Vijaya ◽

K. Tharangini

Keyword(s):

Breast Cancer ◽

Diabetes Mellitus ◽

Cervical Cancer ◽

Communicable Diseases ◽

Screening Tests ◽

Screening Methods ◽

Care Hospital ◽

Test Results ◽

Non Communicable Diseases ◽

Positive Results

Background: This study was conducted to enumerate the results of screening for non-communicable diseases in the NCD clinic over a period of one year in a tertiary health centre.Methods: The results from screening tests conducted in the NCD clinic, for detecting hypertension, diabetes mellitus, breast cancer and cervical cancer, in Government tertiary care Hospital for Women, Chennai, were recorded. The flowchart and screening methods followed were those recommended by the NHM - NPCDCS. Data thus obtained was analyzed using standard statistical methods.Results: Of 42,519 women screened for common non communicable diseases - hypertension, diabetes mellitus, breast cancer and cervical cancer, nearly 5.55% women (n = 2359) had positive results, for any one of the diseases screened. Of 11,708 women screened for diabetes mellitus and 13,971 screened for hypertension, positive results were found in 856 women and 1,216 women respectively. Around 7,568 women were screened for cervical cancer and 175 women tested positive. A large number of 9,272 women were screened for breast cancer and 112 women had positive results. As per the guidelines, women who tested positive for screening tests were referred to the concerned departments in RGGGH.Conclusions: Nearly 42,519 women were screened for common non-communicable diseases (NCDs) - hypertension, diabetes mellitus, breast cancer and cervical cancer, and 5.55% women had positive test results for any one of the diseases screened. The screening revealed, 8.7% of women had raised blood pressure, 7.31% had raised blood sugar levels, 1.21% women had positive screening test results for breast cancer, and 2.31% women for cervical cancer.

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Feasibility and Acceptability of Smartphone-Based Cervical Cancer Screening Among HIV-Positive Women in Western Kenya

JCO Global Oncology ◽

10.1200/go.21.00013 ◽

2021 ◽

pp. 686-693

Author(s):

Chemtai Mungo ◽

Cirilus Ogollah Osongo ◽

Jeniffer Ambaka ◽

Magdalene A. Randa ◽

Benard Samba ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Screening ◽

Cervical Cancer Screening ◽

Intraepithelial Neoplasia ◽

Screening Methods ◽

Cervical Intraepithelial Neoplasia Grade ◽

High Quality ◽

Middle Income ◽

Western Kenya ◽

Low And Middle Income

PURPOSE Adjunct cervical cancer screening methods are under evaluation to improve the diagnostic accuracy of human papillomavirus (HPV)-based screening in low- and middle-income countries. We evaluated the feasibility and acceptability of smartphone-based cervicography among HPV-positive women living with HIV (WLWH) in Western Kenya. METHODS HPV-positive WLWH of 25-49 years of age enrolled in a clinical trial (ClinicalTrials.gov identifier: NCT04191967 ) had digital images of the cervix taken using a smartphone by a nonphysician provider following visual inspection with acetic acid. All participants had colposcopy-directed biopsy before treatment. Cervical images were evaluated by three off-site colposcopists for quality, diagnostic utility, and assigned a presumed diagnosis. We determined the proportion of images rates as low, medium, or high quality, interobserver agreement using Cohen’s Kappa statistic, and the off-site colposcopist’s sensitivity and specificity for diagnosis of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) compared with histopathology. Acceptability was evaluated using a questionnaire. RESULTS One hundred sixty-four HPV-positive WLWH underwent cervicography during the study period. Mean age was 37.3 years. Images from the first 94 participants were evaluated by off-site colposcopists, with a majority (70.9%) rated as high quality. Off-site colposcopists had a sensitivity ranging from 21.4% (95% CI, 0.06 to 0.43) to 35.7% (95% CI, 0.26 to 0.46) and a specificity between 85.5% (95% CI, 0.81 to 0.90) to 94.9% (95% CI, 0.92 to 0.98) for diagnosis of CIN2+ based compared with histopathology. The majority of women, 99.4%, were comfortable having an image of their cervix taken as part of screening. CONCLUSION Cervicography by a nonphysician provider as an adjunct to HPV-based screening among WLWH in a low- and middle-income country setting is feasible and acceptable. However, low sensitivity for diagnosis of CIN2+ by off-site expert colposcopists highlights the limitations of cervicography.

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Awareness and Attitude to the Risk of Cervical Cancer and Screening Methods among Women in the Najran Region of Southern Saudi Arabia

10.21203/rs.3.rs-33070/v1 ◽

2020 ◽

Author(s):

Majed Alshahrani ◽

Salem Ali Alatef Sultan

Keyword(s):

Risk Factors ◽

Cervical Cancer ◽

Pap Smear ◽

Healthcare Providers ◽

Screening Tests ◽

Screening Methods ◽

Sources Of Information ◽

Cross Sectional ◽

Pap Smear Screening ◽

History Of

Abstract Introduction:The aim of this study was determined the level of awareness among women regarding risk factors for cervical cancer and screening methods, their sources of information, and general attitudes toward Pap smear screening tests and human papilloma virus vaccination.Method: A cross-sectional interviewer administered an electronic questionnaire among women in Najran City during the period from March 1, 2019 to June 30, 2019. The data were analyzed using IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.Result: A total of 3,387 women participated in this study. Less than 10% of the participants had good awareness and 70% had poor awareness about the risk factors for cervical cancer. In terms of the major barriers to taking the Pap smear test among married women, 968 (56.7%) had no knowledge of the test and 338 (19.85%) considered it unnecessary. Significant predictors of the level of awareness about cervical cancer and Pap smear testing were identified as the age of women, occupation, family history of cancer, monthly income (P < 0.001) and education level (P = 0.003).Conclusion: we detected a lack of awareness about risk factors for cervical cancer and the benefits of early detection among women in this region. Healthcare providers should implement policies or programs for cervical cancer screening and vaccination throughout all primary healthcare centers.

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Triage of Women Testing Positive With the careHPV Test on Self-Collected Vaginal Samples for Cervical Cancer Screening in a Low-Resource Setting

Journal of Global Oncology ◽

10.1200/jgo.2016.008078 ◽

2018 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Usha Rani Poli ◽

Swarnalata Gowrishankar ◽

Meenakshi Swain ◽

Jose Jeronimo

Keyword(s):

Cervical Cancer ◽

Cervical Intraepithelial Neoplasia ◽

Intraepithelial Neoplasia ◽

Screening Tests ◽

Low Resource Settings ◽

Screening Programs ◽

Low Resource ◽

Incidence And Mortality ◽

Hpv Test

Purpose Human papillomavirus (HPV) DNA screening reduces cervical cancer incidence and mortality in low-resource settings. Self-collected vaginal samples tested with affordable HPV tests such as careHPV can increase the rate of screening in resource-constrained settings. We report the role of visual inspection with acetic acid (VIA) as a triage test for women testing positive with the careHPV test on self-collected vaginal samples. Methods As part of a multicountry demonstration study, 5,207 women 30 to 49 years of age were recruited from urban slums to undergo four cervical screening tests using the careHPV test on self-collected vaginal samples, provider-collected cervical samples, the Papanicolaou test, and VIA. All women who tested positive for any of the screening tests were evaluated with colposcopy and guided biopsies, followed by treatment if any cervical lesions were detected. The data from the 377 women who tested positive for HPV in the self-collected vaginal samples were also analyzed to assess the performance of VIA, conventional cytology, and colposcopy, as triage tests in the detection of cervical cancer and precancerous lesions. Results Nineteen percent of women who tested positive for vaginal HPV (V-HPV) also tested positive with the VIA test; cervical intraepithelial neoplasia 2+ lesions were detected in 58% of these women. In the 30 % of the women who tested positive for V-HPV with cytology triage, cervical intraepithelial neoplasia 2+ lesions were detected in 80% of these women. The colposcopy referrals for women who tested positive for V-HPV were reduced from 7.6% to 1.5% by VIA triage, and to 2.3% by cytology triage. Although the sensitivity was reduced, the positive predictive value improved after triage with VIA and cytology. Conclusion This study reflects the optimal role of VIA triaging for treatment selection of lesions among those who test positive for V-HPV in screen and treat screening programs that use an HPV test in low-resource settings.

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Awareness and Knowledge About Screening Tests for Cervical Cancer in Patient Attending Obstetrics and Gynaecology Out Patient Department at a Tertiary Care Hospital in Lalitpur

Medical Journal of Shree Birendra Hospital ◽

10.3126/mjsbh.v17i2.20019 ◽

2018 ◽

Vol 17 (2) ◽

pp. 12-18

Author(s):

Meenu Maharjan ◽

Heera Tuladhar

Keyword(s):

Cervical Cancer ◽

Health Care Providers ◽

Pap Smear ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Screening Tests ◽

Screening Methods ◽

Care Hospital ◽

Care Providers ◽

Obstetrics And Gynaecology

Introduction: Cervical cancer is the leading cause of cancer deaths for women worldwide. Early diagnosis of cervical cancer may be done by a simple and cost effective technique of Pap smear. The morbidity and mortality could be significantly reduced with an active cervical cancer screening programme.Methods: A cross sectional interview based study was done among 200 patients attending Obstetrics and Gynaecology OPD of one of the tertiary care hospital at Lalitpur, to assess the knowledge and awareness of patient regarding screening methods of cervical cancer and its prevention and early detection. Results: Among all the participants, 76.5% (n-153) were literate and 23.5% (n-47) were illiterate. Only 41% had heard about the Pap test and only 1% had heard about other methods of screening test like VIA(Visual Inspection with Acetic acid). Only 16% think that infection of the genital tract and 12.5% think that multiple partners is the leading cause of cervical cancer. Among them 51% (n-102) think that regular screening will prevent cervical cancer. But only 22.5% (45) had done Pap smear once and 67% did not know the risk factor of cervical cancer. Only 7% had heard of HPV vaccination but did not know details about it.Conclusions: There is very low level of knowledge about cervical cancer, Pap smear and HPV among the participants attending Obstetrics and Gynaecology OPD. For using Pap smear as a preventive method for cervical cancer, it is necessary to inform women about cervical cancer and the Pap smear test. An aggressive campaign with in depth teaching about cervical cancer by media and health care providers is mandatory.

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