NCT07480902 — Comparison Between Liquid-Based Cytology And Molecular Screening For Detecting Precursor Lesions and Cervical Cancer · CancerIndex
Clinical trial · Interventional
Comparison Between Liquid-Based Cytology And Molecular Screening For Detecting Precursor Lesions and Cervical Cancer
Study To Compare The Efficacy Of Cervical Cytology With Molecular Screening For Detecting Reactive Cellular Changes In The Cervix In An Open Population
This study compares how effective is the molecular screening (a blood test) using Pap smear as reference, that is, a comparison of these tests abilities to detect precursor lesions and cervical cancer among women of an open population
Conditions
Conditions (6)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
Condition (as posted)
Mapped entity
Match
Confidence
I) Atypical Squamous Cells of Undetermined Significance (ASC-US)
—
UNRESOLVED
—
II) Atypical Glandular Cells of Uncertain Significance (AGUS)
Screening for reactive cellular changes in the cervix
description
Participants will be drawn from an open population, so they will be asymptomatic for any cervical disease. Based on colposcopy, there will be four clinical groups: negative control (CTR), low-grade squamous intraepithelial lesion (LSIL, CIN-1), high-grade squamous intraepithelial lesion (HSIL, CIN-2/3), and cervical cancer (CC)
interventionNames
Procedure: Physical examination
Other: Liquid-based cytology
Other: Molecular screening
Other: HPV DNA test
Diagnostic Test: Colposcopy
type
OTHER
label
Cervical biopsy
description
Based on colposcopy, participants in the groups LSIL/CIN-1, HSIL/CIN-2/3, and cervical cancer (CC) will be biopsied
interventionNames
Diagnostic Test: Histopathology
Primary outcomes (5)
Eligibility
Eligibility (as posted)
Sex
Female
Minimum age
18 Years
Maximum age
85 Years
Show eligibility criteria text
Inclusion Criteria:
* Be in good general health.
* Age 18-85 years.
* A minimum fast of 6 hours and no more than 12 hours.
* Refrain from sexual intercourse 24 hours before the study.
* Give written informed consent.
Exclusion Criteria:
* Having a subtotal, total, or radical hysterectomy.
* Being pregnant or suspected of being pregnant. A rapid urine test will be performed. If the result is positive, the patient will be excluded from the protocol and referred for prenatal care.
* Being under oncological treatment (chemotherapy, radiotherapy and/or brachytherapy).
* Being on their period.
* Have a previous confirmatory diagnosis of HIV and/or hepatitis infection.
* Having taken antiplatelet medications, e.g., acetylsalicylic acid, at least 24 hours before the study.
Discontinuation Criteria:
* If the participant refuses any of the study procedures.
* If the study gynecologist detects that the participant has had a hysterectomy.
* If the volume of the biological samples is insufficient for testing.
References
Publications (52)
BACKGROUNDMayorga-Bautista, C. D. et al. Prevalence of high-grade intraepithelial lesions in women aged 15-25 years with cytology report of human papillomavirus infection. Ginecol Obstet Mex 89, (2021).
BACKGROUNDSeefoo-Jarquin P, Sosa-Jurado F, Maycotte-Gonzalez P. [Epidemiological Panorama of Cervical Dysplasia in a First-Level Care Unit]. Rev Med Inst Mex Seguro Soc. 2023 Mar 1;61(2):155-162. Spanish. PMID 37201194
BACKGROUNDAraujo, I., Rosales, B., Peña, I. & Araujo Grijalva, I. Sensitivity and Specificity of Cervicouterine Cytology and the PCR-hrHPV test with Histopathological diagnosis, at the "Solon Espinosa Ayala" Hospital, Solca-Quito. Oncología (Ecuador) (2017) doi:10.33821/227.
BACKGROUNDDeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988 Sep;44(3):837-45. PMID 3203132
BACKGROUNDMexican Social Security Institute (IMSS) & Government of Mexico. Clinical Practice Guideline. Treatment of Cervical Cancer at the Second and Third Levels of Care. https://www.imss.gob.mx/sites/all/statics/guiasclinicas/333GER.pdf (2017).
BACKGROUNDHu ZY, Xiao L, Bode AM, Dong Z, Cao Y. Glycolytic genes in cancer cells are more than glucose metabolic regulators. J Mol Med (Berl). 2014 Aug;92(8):837-45. doi: 10.1007/s00109-014-1174-x. Epub 2014 Jun 8. PMID 24906457
BACKGROUNDXue C, Gu X, Li G, Bao Z, Li L. Expression and Functional Roles of Eukaryotic Initiation Factor 4A Family Proteins in Human Cancers. Front Cell Dev Biol. 2021 Nov 19;9:711965. doi: 10.3389/fcell.2021.711965. eCollection 2021. PMID 34869305
BACKGROUNDLi H, Liu J, Shen S, Dai D, Cheng S, Dong X, Sun L, Guo X. Pan-cancer analysis of alternative splicing regulator heterogeneous nuclear ribonucleoproteins (hnRNPs) family and their prognostic potential. J Cell Mol Med. 2020 Oct;24(19):11111-11119. doi: 10.1111/jcmm.15558. Epub 2020 Sep 11.
measure
Liquid-based Cytology results (categorical)
timeFrame
Cervical smear will be taken during the first visit (Day 1). LBC results will be available within a maximum of 20 days after sampling. This test will be performed by a Licensed Clinical laboratory. All participants will be subjected to this test.
description
Cytology's results:
Negative to lesion/malignancy. Negative with inflammation. Negative with sexually transmitted infection. Negative with HPV/Herpes cytopathic changes. Negative with atrophy. Positive with ASC-US. Positive with ASC-H. Positive with AGUS. Positive with CIN-1. Positive with CIN-2. Positive with CIN-3. Positive with carcinoma in situ. Positive with LSIL/HSIL. Positive with adenocarcinoma. Positive with Cancer/Malignancy. Positive with probable lesion/cancer/malignancy.
measure
Molecular screening result (numeric)
timeFrame
Blood samples will be taken during the first visit (Day 1). Molecular screening results will be available within a maximum of 20 days after sampling. All participants will be subjected to this test
description
Molecular screening detects three human protein biomarkers in human sera by Western blot and ELISA. Western blot results are qualitative (band intensity units or IU) and ELISA results are quantitative (ng/mL). The final result for molecular screening test is computed as follows:
Negative. Only if the three independent biomarkers are below their cutoff values.
Positive. If any of the three independent biomarkers is equal to or greater than its cutoff value.
Cutoff values will be calculated using a ROC curve with the gold standard.
measure
HPV test results (categorical)
timeFrame
Cervical smear will be taken during the first visit (Day 1). HPV test results will be available within a maximum of 20 days after sampling. This test will be performed by a Licensed Clinical laboratory. All participants will be subjected to this test.
description
HPV test will detect fifteen different high-risk genotypes by PCR:
HPV-16 genotype. HPV-18 genotype. HPV-pool (including HPV-31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 67, and 68 genotypes).
The final test result will be assigned as follows:
Positive HPV test: If at least one of the fifteen genotypes is detected on the sample.
Negative HPV test: Only if none of the fifteen genotypes are detected on the sample.
measure
Colposcopy diagnosis (categorical)
timeFrame
Colposcopy will be performed during the first visit (Day 1). This diagnostic test will be performed by a licensed gynecologist. All participants will be subjected to this diagnostic test. Colposcopy will be used as a reference test.
description
Colposcopy is the exploration of the female genitalia -vulva, vagina, and cervix- using a lighted magnifying instrument (colposcope). Its accuracy is higher than that of the cytology. If the gynecologist detects/suspects a lesion or malignancy during colposcopy, a biopsy will be drawn for histopathologic analysis.
Colposcopy results:
Negative with no alterations. Negative with inflammation. Negative with condyloma/condylomatosis/HPV. Negative with atrophy. Negative with squamous metaplasia. Negative with ectropion/ectopy/cervical erosion/cervical eversion/glandular eversion.
Negative with Nabothian cysts. Negative with cervical polyp. Negative with Lichen sclerosus. Positive with CIN-1. Positive with CIN-2. Positive with CIN-3. Positive with carcinoma in situ CIN-3. Positive with neoplasia/invasive neoplasia. Positive with LSIL/HSIL. Positive with probable lesion/CIN/LSIL/HSIL.
measure
Histopathology diagnosis (cathegorical)
timeFrame
The biopsy for histopathology will be drawn during the first visit (Day 1). Histopathology is the gold standard for cervical cancer diagnosis. Biopsies will be drawn only from women with positive colposcopy results.
description
Histopathology is the microscopic analysis of a stained slide of a cervical biopsy by a licensed pathologist. The standard staining is H\&E (hematoxylin and eosin).
Histopathology results:
Negative with normal tissue. Negative with cervicitis. Negative with HPV/Herpes infection. Positive with CIN-1. Positive with CIN-2. Positive with CIN-3. Positive with carcinoma in situ CIN-3. Positive LSIL/HSIL. Positive with microinvasive/invasive cancer. Positive with adenocarcinoma. Positive with sarcoma and other tumors. Positive with carcinoma of unknown primary origin/unspecified malignancy.
Secondary outcomes (15)
measure
Age (numeric)
timeFrame
During the first visit (Day 1).
description
The study physician will record the participants date of birth. Age (in years) will be calculated in reference to the first visit date.
measure
Body Mass Index BMI (numeric)
timeFrame
During the first visit (Day 1).
description
The study physician will record the participants:
Weight in kilograms (kg). Height in meters (m). The Body Mass Index will be calculated as follows: BMI = kg/m\^2.
measure
Blood pressure (numeric)
timeFrame
During the first visit (Day 1).
description
Blood pressure is the amount of force the blood uses to get through the circulatory system measured in mmHg. It consists of two measurements:
Systolic pressure, e.g., 120 mmHg. Diastolic pressure, e.g., 80 mmHg. The final result will display the two independent measurements, e.g., 120/80 mmHg.
measure
Ethnicity (categorical)
timeFrame
During the first visit (Day 1) by clinical interview.
description
Ethnicity data will be obtained through clinical interview. Ethnicity is linked to cultural expression and identity.
Ethnicity options:
Hispanic/Latino. Not Hispanic/Latino.
measure
Race (categorical)
timeFrame
During the first visit (Day 1) by clinical interview.
description
Race data will be obtained through clinical interview. Race is linked to physical characteristics.
Race options:
American Indian. Alaska Native. Asian. Black or African American. African Mexican. Native Hawaiian or Other Pacific Islander. Mexican Original People. White.
measure
Age at Menarche (numeric)
timeFrame
During the first visit (Day 1) by clinical interview.
description
Age at menarche -in years- will be obtained during the clinical interview. Menarche is the first menstrual period in a female adolescent, typically occurs between the ages of 10 and 16.
measure
Age at sexual debut (numeric)
timeFrame
During the first visit (Day 1) by clinical interview.
description
The age at sexual debut -in years- will be obtained during the clinical interview. The age will be recorded in years.
measure
Number of years since menarche to sexual debut (numeric)
timeFrame
During the first visit (Day 1) by clinical interview.
description
The number of years since menarche to sexual debut will be calculated as follows:
NYSMSD = Age of Sexual Debut - Age of Menarche.
measure
Number of lifetime sexual partners (numeric)
timeFrame
During the first visit (Day 1) by clinical interview.
description
The number of lifetime sexual partners of the participants will be obtained during the clinical interview.
measure
Number of years since last cytology (numeric)
timeFrame
During the first visit (Day 1) by clinical interview.
description
The year of last or previous cytology will be obtained during the clinical interview. The number of years since las cytology will be calculated as follows:
NYSLCy =Year of Participation in the Study - Year of Last/Previous Cytology.
measure
Number of years since colposcopy (numeric)
timeFrame
During the first visit (Day 1) by clinical interview.
description
The year of last or previous colposcopy will be obtained during the clinical interview. The number of years since last colposcopy will be calculated as follows:
NYSLCo =Year of Participation in the Study - Year of Last/Previous Colposcopy.
measure
Number of abortions (numeric)
timeFrame
During the first visit (Day 1) by clinical interview.
description
The number of abortions will be obtained during the clinical interview.
measure
Number of vaginal deliveries (numeric)
timeFrame
During the first visit (Day 1) by clinical interview.
description
The number of vaginal deliveries will be obtained during the clinical interview.
measure
Number of Caesarean sections (numeric)
timeFrame
During the first visit (Day 1) by clinical interview.
description
The number of Caesarean sections will be obtained during the clinical interview.
measure
Number of cigarettes per week (numeric)
timeFrame
During the first visit (Day 1) by clinical interview.
description
The number of cigarettes per week will be obtained during the clinical interview.
BACKGROUNDDreyfuss G, Matunis MJ, Pinol-Roma S, Burd CG. hnRNP proteins and the biogenesis of mRNA. Annu Rev Biochem. 1993;62:289-321. doi: 10.1146/annurev.bi.62.070193.001445. No abstract available. PMID 8352591
BACKGROUNDReyes-Hernández, D. O. et al. Novel Serum Protein Biomarkers for Precancerous Cervical Lesions and Cervical Cancer. Glob J Health Sci 16, 44 (2024).
BACKGROUNDCheca-Rojas A, Delgadillo-Silva LF, Velasco-Herrera MDC, Andrade-Dominguez A, Gil J, Santillan O, Lozano L, Toledo-Leyva A, Ramirez-Torres A, Talamas-Rohana P, Encarnacion-Guevara S. GSTM3 and GSTP1: novel players driving tumor progression in cervical cancer. Oncotarget. 2018 Apr 24;9(31):21696-21714. doi: 10.18632/oncotarget.24796. eCollection 2018 Apr 24. PMID 29774096
BACKGROUNDWorld Health Organization & Regional Office for Africa. PapsAI. https://innov.afro.who.int/global-innovation/papsai-3899 (2023).
BACKGROUNDGlobal Auto Systems LTD. Paps AI. https://papsai.com/index.html#about (2020).
BACKGROUNDWilliam, W., Ware, A., Basaza-Ejiri, A. H. & Obungoloch, J. Automated diagnosis and classification of cervical cancer from Pap-smear images. in 2019 IST-Africa Week Conference, IST-Africa 2019 (Institute of Electrical and Electronics Engineers Inc., 2019). doi:10.23919/ISTAFRICA.2019.8764887.
BACKGROUNDWilliam, W., Ware, A., Basaza-Ejiri, A. H. & Obungoloch, J. Cervical cancer classification from Pap-smears using an enhanced fuzzy C-means algorithm. Inform Med Unlocked 14, 23-33 (2019).
BACKGROUNDWilliam W, Ware A, Basaza-Ejiri AH, Obungoloch J. A pap-smear analysis tool (PAT) for detection of cervical cancer from pap-smear images. Biomed Eng Online. 2019 Feb 12;18(1):16. doi: 10.1186/s12938-019-0634-5. PMID 30755214
BACKGROUNDShin MB, Garcia PJ, Saldarriaga EM, Fiestas JL, Asbjornsdottir KH, Iribarren SJ, Barnabas RV, Gimbel S. Cost of community-based human papillomavirus self-sampling in Peru: A micro-costing study. Lancet Reg Health Am. 2022 Apr;8:100160. doi: 10.1016/j.lana.2021.100160. Epub 2021 Dec 29. PMID 35528707
BACKGROUNDGiannella L, Di Giuseppe J, Delli Carpini G, Grelloni C, Fichera M, Sartini G, Caimmi S, Natalini L, Ciavattini A. HPV-Negative Adenocarcinomas of the Uterine Cervix: From Molecular Characterization to Clinical Implications. Int J Mol Sci. 2022 Nov 30;23(23):15022. doi: 10.3390/ijms232315022. PMID 36499345
BACKGROUNDJenkins D, Molijn A, Kazem S, Pirog EC, Alemany L, de Sanjose S, Dinjens W, Quint W. Molecular and pathological basis of HPV-negative cervical adenocarcinoma seen in a global study. Int J Cancer. 2020 Nov 1;147(9):2526-2536. doi: 10.1002/ijc.33124. Epub 2020 Jul 6. PMID 32474915
BACKGROUNDLee JE, Chung Y, Rhee S, Kim TH. Untold story of human cervical cancers: HPV-negative cervical cancer. BMB Rep. 2022 Sep;55(9):429-438. doi: 10.5483/BMBRep.2022.55.9.042. PMID 35725012
BACKGROUNDMexican Social Security Institute (IMSS) & Government of Mexico. Clinical Practice Guideline. Prevention and early detection of cervical cancer. At the primary care level. https://www.imss.gob.mx/sites/all/statics/guiasclinicas/146GER.pdf (2011).
BACKGROUNDWHO guideline for screening and treatment of cervical pre-cancer lesions for cervical cancer prevention [Internet]. 2nd edition. Geneva: World Health Organization; 2021. Available from http://www.ncbi.nlm.nih.gov/books/NBK572317/ PMID 34314129
BACKGROUNDNajib FS, Hashemi M, Shiravani Z, Poordast T, Sharifi S, Askary E. Diagnostic Accuracy of Cervical Pap Smear and Colposcopy in Detecting Premalignant and Malignant Lesions of Cervix. Indian J Surg Oncol. 2020 Sep;11(3):453-458. doi: 10.1007/s13193-020-01118-2. Epub 2020 Jun 23. PMID 33013127
BACKGROUNDMayrand MH, Duarte-Franco E, Rodrigues I, Walter SD, Hanley J, Ferenczy A, Ratnam S, Coutlee F, Franco EL; Canadian Cervical Cancer Screening Trial Study Group. Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med. 2007 Oct 18;357(16):1579-88. doi: 10.1056/NEJMoa071430. PMID 17942871
BACKGROUNDKitchener HC, Castle PE, Cox JT. Chapter 7: Achievements and limitations of cervical cytology screening. Vaccine. 2006 Aug 31;24 Suppl 3:S3/63-70. doi: 10.1016/j.vaccine.2006.05.113. PMID 16950019
BACKGROUNDColeman, D. Limitations of the cervical smear test as a method of detecting women at risk of cervical cancer. AVMA Medical & Legal Journal 235 The AVMA Medical & Legal Journal 7, (2001).
BACKGROUNDBravington A, Chen H, Dyson J, Jones L, Dalgliesh C, Bryan A, Patnick J, Macleod U. Challenges and opportunities for cervical screening in women over the age of 50 years: a qualitative study. Br J Gen Pract. 2022 Nov 24;72(725):e873-e881. doi: 10.3399/BJGP.2022.0036. Print 2022 Dec. PMID 36192359
BACKGROUNDShin HY, Song SY, Jun JK, Kim KY, Kang P. Barriers and strategies for cervical cancer screening: What do female university students know and want? PLoS One. 2021 Oct 5;16(10):e0257529. doi: 10.1371/journal.pone.0257529. eCollection 2021. PMID 34610022
BACKGROUNDPetersen Z, Jaca A, Ginindza TG, Maseko G, Takatshana S, Ndlovu P, Zondi N, Zungu N, Varghese C, Hunting G, Parham G, Simelela P, Moyo S. Barriers to uptake of cervical cancer screening services in low-and-middle-income countries: a systematic review. BMC Womens Health. 2022 Dec 2;22(1):486. doi: 10.1186/s12905-022-02043-y. PMID 36461001
BACKGROUNDAkinlotan M, Bolin JN, Helduser J, Ojinnaka C, Lichorad A, McClellan D. Cervical Cancer Screening Barriers and Risk Factor Knowledge Among Uninsured Women. J Community Health. 2017 Aug;42(4):770-778. doi: 10.1007/s10900-017-0316-9. PMID 28155005
BACKGROUNDMexican Ministry of Health. NOM-014-SSA2-1994. For the prevention, detection, diagnosis, treatment, control and epidemiological surveillance of cervical cancer. https://www.gob.mx/cms/uploads/attachment/file/10397/NOM-014-SSA2-1994.pdf (2007).
BACKGROUNDInternational Agency for Research on Cancer. CanScreen5. Cervical Cancer Screening Programme. Country Fact Sheet: Mexico. https://canscreen5.iarc.fr/?page=countryfactsheetcervix&q=MEX&rc= (2021).
BACKGROUNDZhang L, Mosquera I, Lucas E, Rol ML, Carvalho AL, Basu P; CanScreen5 collaborators. CanScreen5, a global repository for breast, cervical and colorectal cancer screening programs. Nat Med. 2023 May;29(5):1135-1145. doi: 10.1038/s41591-023-02315-6. Epub 2023 Apr 27. PMID 37106168
BACKGROUNDMitra A, Tzafetas M, Lyons D, Fotopoulou C, Paraskevaidis E, Kyrgiou M. Cervical intraepithelial neoplasia: screening and management. Br J Hosp Med (Lond). 2016 Aug 2;77(8):C118-23. doi: 10.12968/hmed.2016.77.8.C118. No abstract available. PMID 27487071
BACKGROUNDSellors JW & Sankaranarayanan R. An introduction to Cervical Intraepithelial Neoplasia (CIN). in Colposcopy and treatment of cervical intraepithelial neoplasia: a beginners manual 1-140 (Centro Internacional de Investigaciones sobre el Cáncer (IARC), Lyon, Francia, 2003).
BACKGROUNDAlimena S, Davis J, Fichorova RN, Feldman S. The vaginal microbiome: A complex milieu affecting risk of human papillomavirus persistence and cervical cancer. Curr Probl Cancer. 2022 Aug;46(4):100877. doi: 10.1016/j.currproblcancer.2022.100877. Epub 2022 Jun 9. PMID 35709613
BACKGROUNDJohnson CA, James D, Marzan A, Armaos M. Cervical Cancer: An Overview of Pathophysiology and Management. Semin Oncol Nurs. 2019 Apr;35(2):166-174. doi: 10.1016/j.soncn.2019.02.003. Epub 2019 Mar 14. PMID 30878194
BACKGROUNDRibeiro AA, Costa MC, Alves RR, Villa LL, Saddi VA, Carneiro MA, Zeferino LC, Rabelo-Santos SH. HPV infection and cervical neoplasia: associated risk factors. Infect Agent Cancer. 2015 May 26;10:16. doi: 10.1186/s13027-015-0011-3. eCollection 2015. PMID 26244052
BACKGROUNDVesco KK, Whitlock EP, Eder M, Burda BU, Senger CA, Lutz K. Risk factors and other epidemiologic considerations for cervical cancer screening: a narrative review for the U.S. Preventive Services Task Force. Ann Intern Med. 2011 Nov 15;155(10):698-705, W216. doi: 10.7326/0003-4819-155-10-201111150-00377. Epub 2011 Oct 17. PMID 22006929
BACKGROUNDInternational Collaboration of Epidemiological Studies of Cervical Cancer; Appleby P, Beral V, Berrington de Gonzalez A, Colin D, Franceschi S, Goodhill A, Green J, Peto J, Plummer M, Sweetland S. Cervical cancer and hormonal contraceptives: collaborative reanalysis of individual data for 16,573 women with cervical cancer and 35,509 women without cervical cancer from 24 epidemiological studies. Lancet. 2007 Nov 10;370(9599):1609-21. doi: 10.1016/S0140-6736(07)61684-5. PMID 17993361
BACKGROUNDInternational Collaboration of Epidemiological Studies of Cervical Cancer. Cervical carcinoma and sexual behavior: collaborative reanalysis of individual data on 15,461 women with cervical carcinoma and 29,164 women without cervical carcinoma from 21 epidemiological studies. Cancer Epidemiol Biomarkers Prev. 2009 Apr;18(4):1060-9. doi: 10.1158/1055-9965.EPI-08-1186. Epub 2009 Mar 31. PMID 19336546
BACKGROUNDInternational Collaboration of Epidemiological Studies of Cervical Cancer. Comparison of risk factors for invasive squamous cell carcinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiological studies. Int J Cancer. 2007 Feb 15;120(4):885-91. doi: 10.1002/ijc.22357. PMID 17131323
BACKGROUNDPlummer M, Herrero R, Franceschi S, Meijer CJ, Snijders P, Bosch FX, de Sanjose S, Munoz N; IARC Multi-centre Cervical Cancer Study Group. Smoking and cervical cancer: pooled analysis of the IARC multi-centric case--control study. Cancer Causes Control. 2003 Nov;14(9):805-14. doi: 10.1023/b:caco.0000003811.98261.3e. PMID 14682438
BACKGROUNDCollins S, Rollason TP, Young LS, Woodman CB. Cigarette smoking is an independent risk factor for cervical intraepithelial neoplasia in young women: a longitudinal study. Eur J Cancer. 2010 Jan;46(2):405-11. doi: 10.1016/j.ejca.2009.09.015. Epub 2009 Oct 12. PMID 19819687
BACKGROUNDTekalegn Y, Sahiledengle B, Woldeyohannes D, Atlaw D, Degno S, Desta F, Bekele K, Aseffa T, Gezahegn H, Kene C. High parity is associated with increased risk of cervical cancer: Systematic review and meta-analysis of case-control studies. Womens Health (Lond). 2022 Jan-Dec;18:17455065221075904. doi: 10.1177/17455065221075904. PMID 35114865
BACKGROUNDBezabih M, Tessema F, Sengi H, Deribew A. Risk Factors Associated with Invasive Cervical Carcinoma among Women Attending Jimma University Specialized Hospital, Southwest Ethiopia: A Case Control Study. Ethiop J Health Sci. 2015 Oct;25(4):345-52. doi: 10.4314/ejhs.v25i4.8. PMID 26949299
BACKGROUNDMcGraw SL, Ferrante JM. Update on prevention and screening of cervical cancer. World J Clin Oncol. 2014 Oct 10;5(4):744-52. doi: 10.5306/wjco.v5.i4.744. PMID 25302174
BACKGROUNDHwang LY, Ma Y, Benningfield SM, Clayton L, Hanson EN, Jay J, Jonte J, Godwin de Medina C, Moscicki AB. Factors that influence the rate of epithelial maturation in the cervix in healthy young women. J Adolesc Health. 2009 Feb;44(2):103-110. doi: 10.1016/j.jadohealth.2008.10.006. PMID 19167657
BACKGROUNDRuiz AM, Ruiz JE, Gavilanes AV, Eriksson T, Lehtinen M, Perez G, Sings HL, James MK, Haupt RM; FUTURE I and II Study Group. Proximity of first sexual intercourse to menarche and risk of high-grade cervical disease. J Infect Dis. 2012 Dec 15;206(12):1887-96. doi: 10.1093/infdis/jis612. Epub 2012 Oct 12. PMID 23066159
BACKGROUNDWorld Health Organization. Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem. https://www.who.int/publications/i/item/9789240014107 (2020).
BACKGROUNDWorld Health Organization & International Agency for Research on Cancer. Global Cancer Observatory. https://gco.iarc.fr/today/home
BACKGROUNDMok, S. C., Wong, K. K., Lu, K. H., Munger, K. & Nagymanyoki, Z. Molecular basis of gynecologic diseases. in Essential Concepts in Molecular Pathology 409-424 (Elsevier, 2020). doi:10.1016/B978-0-12-813257-9.00023-1.