Moscicki A-B, Shiboski S, Broering J, Powell K, Clayton L, Jay N, et al. The natural history of human papillomavirus infection as measured by repeated DNA testing in adolescent and young women. J Pediatrics. 1998;132:277–84.
Google ScholarÂ
Stanley M. Immune responses to human papillomavirus. Vaccine. 2006;24:S16–S22.
Google ScholarÂ
Kyrgiou M, Arbyn M, Bergeron C, Bosch FX, Dillner J, Jit M, et al. Cervical screening: ESGO-EFC position paper of the European Society of Gynaecologic Oncology (ESGO) and the European Federation of Colposcopy (EFC). Br J Cancer. 2020;123:510–7.
Google ScholarÂ
Ellis LB, Bowden SJ, Lyons D, Kyrgiou M, the Royal College of Obstetricians and G. SIP 7: Progress in Cervical Cancer Prevention in the UK (2025 Second Edition). BJOG: An International J Obstetr Gynaecol. 2025;n/a(n/a).
Bruni L, Serrano B, Roura E, Alemany L, Cowan M, Herrero R, et al. Cervical cancer screening programmes and age-specific coverage estimates for 202 countries and territories worldwide: a review and synthetic analysis. Lancet Glob Health. 2022;10:e1115–e27.
Google ScholarÂ
Kilby MD, Luesley DM, Ellis LB, Martin-Hirsch P, Kyrgiou M. Cervical Intraepithelial Neoplasia and Screening2025. 703-10 p.
Graham V. Sheila. The human papillomavirus replication cycle, and its links to cancer progression: a comprehensive review. Clin Sci. 2017;131:2201–21.
Google ScholarÂ
England N. 4. Colposcopic diagnosis, treatment and follow up. gov.uk; 2023.
Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F, et al. 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors. J Low Genit Trac Dis. 2020;24:102–31.
Google ScholarÂ
Ostör AG. Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol. 1993;12:186–92.
Google ScholarÂ
Sharpless KE, Marcus JZ, Kuroki LM, Wiser AL, Flowers L. ASCCP committee opinion: adjuvant human papillomavirus vaccine for patients undergoing treatment for cervical intraepithelial neoplasia. J Low Genit Trac Dis. 2023;27:93–6.
Google ScholarÂ
McCredie MR, Sharples KJ, Paul C, Baranyai J, Medley G, Jones RW, et al. Natural history of cervical neoplasia and risk of invasive cancer in women with cervical intraepithelial neoplasia 3: a retrospective cohort study. Lancet Oncol. 2008;9:425–34.
Google ScholarÂ
Galgano MT, Castle PE, Atkins KA, Brix WK, Nassau SR, Stoler MH. Using biomarkers as objective standards in the diagnosis of cervical biopsies. Am J Surgical Pathol. 2010;34:1077–87.
Google ScholarÂ
Tainio K, Athanasiou A, Tikkinen KAO, Aaltonen R, Cárdenas J, Hernándes, et al. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. BMJ. 2018:k499.
Lycke KD, Kahlert J, Damgaard RK, Eriksen DO, Bennetsen MH, Gravitt PE, et al. CLINICAL COURSE OF CERVICAL INTRAEPITHELIAL NEOPLASIA GRADE 2 A POPULATION-BASED COHORT STUDY. American journal of obstetrics and gynecology. 2023.
Kyrgiou M, Athanasiou A, Paraskevaidi M, Mitra A, Kalliala I, Martin-Hirsch P, et al. Adverse obstetric outcomes after local treatment for cervical preinvasive and early invasive disease according to cone depth: systematic review and meta-analysis. BMJ. 2016:i3633.
Kyrgiou M, Mitra A, Arbyn M, Paraskevaidi M, Athanasiou A, Martin-Hirsch PP, et al. Fertility and early pregnancy outcomes after conservative treatment for cervical intraepithelial neoplasia. Cochrane Database Syst Rev. 2015;2015:Cd008478.
Google ScholarÂ
Kyrgiou M, Mitra A, Arbyn M, Stasinou SM, Martin-Hirsch P, Bennett P, et al. Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis. BMJ. 2014;349:g6192–g.
Google ScholarÂ
Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Paraskevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet. 2006;367:489–98.
Google ScholarÂ
Athanasiou A, Veroniki AA, Efthimiou O, Kalliala I, Naci H, Bowden S, et al. Comparative effectiveness and risk of preterm birth of local treatments for cervical intraepithelial neoplasia and stage IA1 cervical cancer: a systematic review and network meta-analysis. Lancet Oncol. 2022;23:1097–108.
Google ScholarÂ
Lycke KD, Kahlert J, Petersen LK, Damgaard RK, Cheung LC, Gravitt PE, et al. Untreated cervical intraepithelial neoplasia grade 2 and subsequent risk of cervical cancer: population based cohort study. BMJ. 2023:e075925.
Kyrgiou M, Bowden SJ, Ellis LB, Hammer A, Lyons D, Freeman-Wang T, et al. Active surveillance of cervical intraepithelial neoplasia grade 2: 2025 British Society of Colposcopy and Cervical Pathology and European Society of Gynaecologic Oncology consensus statement. Lancet Oncol. 2025;26:e140–e51.
Google ScholarÂ
Damgaard R, Jenkins D, Stoler M, de Koning M, van de Sandt M, Lycke K, et al. HPV genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. American Journal of Obstetrics and Gynecology 2024.
Guan P, Howell-Jones R, Li N, Bruni L, De Sanjosé S, Franceschi S, et al. Human papillomavirus types in 115,789 HPV-positive women: A meta-analysis from cervical infection to cancer. Int J Cancer. 2012;131:2349–59.
Google ScholarÂ
Wentzensen N, Schwartz L, Zuna RE, Smith K, Mathews C, Gold MA, et al. Performance of p16/Ki-67 Immunostaining to Detect Cervical Cancer Precursors in a Colposcopy Referral Population. Clin Cancer Res. 2012;18:4154–62.
Google ScholarÂ
Bruno MT, Scalia G, Cassaro N, Costanzo M, Boemi S. Conservative management of CIN2 p16 positive lesions in women with multiple HPV infection. BMC Infectious Diseases. 2020;20.
Castle PE, Adcock R, Cuzick J, Wentzensen N, Torrez-Martinez NE, Torres SM, et al. Relationships of p16 Immunohistochemistry and Other Biomarkers With Diagnoses of Cervical Abnormalities: Implications for LAST Terminology. Arch Pathol Lab Med. 2020;144:725–34.
Google ScholarÂ
Moscicki A-B, Ma Y, Wibbelsman C, Darragh TM, Powers A, Farhat S, et al. Rate of and Risks for Regression of Cervical Intraepithelial Neoplasia 2 in Adolescents and Young Women. Obstet Gynecol. 2010;116:1373–80.
Google ScholarÂ
Louvanto K, Aro K, Nedjai B, Bützow R, Jakobsson M, Kalliala I, et al. Methylation in Predicting Progression of Untreated High-grade Cervical Intraepithelial Neoplasia. Clin Infect Dis. 2020;70:2582–90.
Google ScholarÂ
Moore LD, Le T, Fan G. DNA Methylation and Its Basic Function. Neuropsychopharmacology. 2013;38:23–38.
Google ScholarÂ
Jin B, Li Y, Robertson KD. DNA Methylation: Superior or Subordinate in the Epigenetic Hierarchy? Genes Cancer. 2011;2:607–17.
Google ScholarÂ
Yong W-S, Hsu F-M, Chen P-Y. Profiling genome-wide DNA methylation. Epigenetics & Chromatin. 2016;9.
Saghafinia S, Mina M, Riggi N, Hanahan D, Ciriello G. Pan-Cancer Landscape of Aberrant DNA Methylation across Human Tumors. Cell Rep. 2018;25:1066–80.e8.
Google ScholarÂ
Baylin SB. Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer. Hum Mol Genet. 2001;10:687–92.
Google ScholarÂ
Mccabe MT, Brandes JC, Vertino PM. Cancer DNA methylation: molecular mechanisms and clinical implications. Clin Cancer Res. 2009;15:3927–37.
Google ScholarÂ
Levenson VV. DNA methylation as a universal biomarker. Expert Rev Mol Diagnostics. 2010;10:481–8.
Google ScholarÂ
Baylin SB, Jones PA. Epigenetic determinants of cancer. Cold Spring Harb Perspect Biol. 2016;8:a019505.
Google ScholarÂ
Van Veldhoven K, Polidoro S, Baglietto L, Severi G, Sacerdote C, Panico S, et al. Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis. Clinical Epigenetics. 2015;7.
Chen Y, Hu F, Zhou Y, Chen W, Shao H, Zhang Y. MGMT promoter methylation and glioblastoma prognosis: a systematic review and meta-analysis. Arch Med Res. 2013;44:281–90.
Google ScholarÂ
Barrett JE, Sundstrom K, Jones A, Evans I, Wang J, Herzog C, et al. The WID-CIN test identifies women with, and at risk of, cervical intraepithelial neoplasia grade 3 and invasive cervical cancer. Genome Med. 2022;14:116.
Google ScholarÂ
Herzog C, Sundstrom K, Jones A, Evans I, Barrett JE, Wang J, et al. DNA methylation-based detection and prediction of cervical intraepithelial neoplasia grade 3 and invasive cervical cancer with the WID TM-qCIN test. Clin epigenetics. 2022;14:150.
Google ScholarÂ
Bowden SJ, Ellis LB, Kalliala I, Paraskevaidi M, Tighe J, Kechagias KS, et al. Protocol for a systematic review and meta-analysis of the diagnostic test accuracy of host and HPV DNA methylation in cervical cancer screening and management. BMJ Open. 2023;13:e071534.
Google ScholarÂ
Bowden SJ, Kalliala I, Veroniki AA, Arbyn M, Mitra A, Lathouras K, et al. The use of human papillomavirus DNA methylation in cervical intraepithelial neoplasia: A systematic review and meta-analysis. EBioMedicine. 2019;50:246–59.
Google ScholarÂ
Kremer WW, Dick S, Heideman DAM, Steenbergen RDM, Bleeker MCG, Verhoeve HR, et al. Clinical Regression of High-Grade Cervical Intraepithelial Neoplasia Is Associated With Absence of FAM19A4/miR124-2 DNA Methylation (CONCERVE Study). J Clin Oncol. 2022;40:3037–46.
Google ScholarÂ
Xu Y, Tsai C-W, Chang W-S, Han Y, Huang M, Pettaway CA, et al. Epigenome-wide association study of prostate cancer in african americans identifies DNA methylation biomarkers for aggressive disease. Biomolecules. 2021;11:1826.
Google ScholarÂ
Flanagan JM, Wilson A, Koo C, Masrour N, Gallon J, Loomis E, et al. Platinum-Based Chemotherapy Induces Methylation Changes in Blood DNA Associated with Overall Survival in Patients with Ovarian Cancer. Clin Cancer Res. 2017;23:2213–22.
Google ScholarÂ
Bowden SJ, Bodinier B, Paraskevaidi M, Kalliala I, Nasioutziki M, Ellis LB, et al. DNA methylation signatures of cervical pre-invasive and invasive disease: An epigenome-wide association study. Int J. Cancer. 2025;n/a(n/a).
Bukowski A, Hoyo C, Vielot NA, Graff M, Kosorok MR, Brewster WR, et al. Epigenome-wide methylation and progression to high-grade cervical intraepithelial neoplasia (CIN2+): a prospective cohort study in the United States. BMC Cancer. 2023;23.
Muzio G, Maggiora M, Paiuzzi E, Oraldi M, Canuto RA. Aldehyde dehydrogenases and cell proliferation. Free Radic Biol Med. 2012;52:735–46.
Google ScholarÂ
Xia J, Li S, Liu S, Zhang L. Aldehyde dehydrogenase in solid tumors and other diseases: Potential biomarkers and therapeutic targets. MedComm. 2023;4.
Zhou R, Chen Z, Xiao Z-R, Wang S-L, Rong C. HPV-Related Promoter Methylation-Based Gene Signature Predicts Clinical Prognosis of Patients With Cervical Cancer. Frontiers in Oncology. 2021;11.
Senchenko VN, Kisseljova NP, Ivanova TA, Dmitriev AA, Krasnov GS, Kudryavtseva AV, et al. Novel tumor suppressor candidates on chromosome 3 revealed by NotI-microarrays in cervical cancer. Epigenetics. 2013;8:409–20.
Google ScholarÂ
Atlas THP. ALDH9A1. 2024.
Cánovas V, Lleonart M, Morote J, Paciucci R. The role of prostate tumor overexpressed 1 in cancer progression. Oncotarget. 2017;8:12451–71.
Google ScholarÂ
Verger A, Baert J-L, Verreman K, Dewitte F, Ferreira E, Lens Z, et al. The Mediator complex subunit MED25 is targeted by the N-terminal transactivation domain of the PEA3 group members. Nucleic Acids Res. 2013;41:4847–59.
Google ScholarÂ
Jo YS, Kim MS, Yoo NJ, Lee SH. Frameshift Mutation of MED25, a Transcription Regulator, and its Mutational Heterogeneity in Colorectal Cancers. Pathol Oncol Res. 2016;22:875–6.
Google ScholarÂ
Atlas THP. MED25: Cervical cancer. 2024. https://www.proteinatlas.org/ENSG00000104973-MED25/cancer.
Aguilar X, Blomberg J, Brännström K, Olofsson A, Schleucher J, Björklund S. Interaction Studies of the Human and Arabidopsis thaliana Med25-ACID Proteins with the Herpes Simplex Virus VP16- and Plant-Specific Dreb2a Transcription Factors. PLoS ONE. 2014;9:e98575.
Google ScholarÂ
Dong J, Basse V, Bierre M, Peres de Oliveira A, Vidalain P-O, Sibille P, et al. Respiratory Syncytial Virus NS1 Protein Targets the Transactivator Binding Domain of MED25. J Mol Biol. 2022;434:167763.
Google ScholarÂ
Ruyechan WT. Roles of Cellular Transcription Factors in VZV Replication. In: Abendroth A, Arvin AM, Moffat JF, editors. Varicella-zoster Virus. Berlin, Heidelberg: Springer Berlin Heidelberg; 2010. p. 43-65.
Rovnak J, Quackenbush SL. Exploitation of the Mediator complex by viruses. PLOS Pathog. 2022;18:e1010422.
Google ScholarÂ
Atlas THP. MED25: Head and neck cancer. 2024. https://www.proteinatlas.org/ENSG00000104973-MED25/cancer.
GTex. TULP2. 2024. https://www.gtexportal.org/home/gene/TULP2.
Atlas THP. TULP2: Pathology. 2024. https://www.proteinatlas.org/ENSG00000104804-TULP2/cancer.
plus P. Tubby-like protein 2. 2024. https://www.proteinatlas.org/ENSG00000104804-TULP2.
Atlas THP. TULP2: Immune. 2024. https://www.proteinatlas.org/ENSG00000104804-TULP2.
Fausch SC, Da Silva DM, Kast WM. Differential Uptake and Cross-Presentation of Human Papillomavirus Virus-like Particles by Dendritic Cells and Langerhans Cells1. Cancer Res. 2003;63:3478–82.
Google ScholarÂ
Zhu H, Zhu H, Tian M, Wang D, He J, Xu T. DNA Methylation and Hydroxymethylation in Cervical Cancer: Diagnosis, Prognosis and Treatment. Frontiers in Genetics. 2020;11.
Lorincz AT, Brentnall AR, Scibior-Bentkowska D, Reuter C, Banwait R, Cadman L, et al. Validation of a DNA methylation HPV triage classifier in a screening sample. Int J cancer. 2016;138:2745–51.
Google ScholarÂ
Bonde J, Floore A, Ejegod D, Vink FJ, Hesselink A, van de Ven PM, et al. Methylation markers FAM19A4 and miR124-2 as triage strategy for primary human papillomavirus screen positive women: A large European multicenter study. Int J cancer. 2021;148:396–405.
Google ScholarÂ
Hoyer H, Stolte C, Böhmer G, Hampl M, Hagemann I, Maier E, et al. Evaluation of CIN2/3 Lesion Regression in GynTect® DNA Methylation-Marker-Negative Patients in a Longitudinal Study. Cancers. 2023;15:3951.
Google ScholarÂ
Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 2018;19:371–84.
Google ScholarÂ
Horvath S. DNA methylation age of human tissues and cell types. Genome Biol. 2013;14:3156.
Google ScholarÂ
Singh N, Gilks BC, Wing-Cheuk Wong R, McCluggage GW, Herrington SC. Interpretation of p16 Immunohistochemistry In Lower Anogenital Tract Neoplasia 2022 [Available from: https://www.thebagp.org/download/interpretation-of-p16-immunohistochemistry-in-lower-anogenital-tract-neoplasia/.
Loopik DL, Bentley HA, Eijgenraam MN, IntHout J, Bekkers RLM, Bentley JR. The natural history of cervical intraepithelial neoplasia grades 1, 2, and 3: a systematic review and meta-analysis. J Low Genit Trac Dis. 2021;25:221–31.
Google ScholarÂ
Loopik DL, Bekkers RLM, Massuger LFAG, Melchers WJG, Siebers AG, Bentley J. Justifying conservative management of CIN2 in women younger than 25 years – A population-based study. Gynecologic Oncol. 2019;152:82–6.
Google ScholarÂ
Loopik DL, Doucette S, Bekkers RLM, Bentley JR. Regression and progression predictors of CIN2 in women younger than 25 years. J Lower Genital Tract Dis. 2016;20.
Skorstengaard M, Lynge E, Suhr J, Napolitano G. Conservative management of women with cervical intraepithelial neoplasia grade 2 in Denmark: a cohort study. BJOG: Int J Obstet Gynaecol. 2020;127:729–36.
Google ScholarÂ
Damgaard RK, Jenkins D, Stoler MH, de Koning M, van de Sandt M, Lycke KD, et al. Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. Am J Obstet Gynecol. 2024;230:655.e1–e10.
Google ScholarÂ
Bergqvist L, Virtanen A, Kalliala I, Bützow R, Jakobsson M, Heinonen A, et al. Predictors for regression and progression of actively surveilled cervical intraepithelial neoplasia grade 2: A prospective cohort study. Acta Obstetricia et Gynecologica Scandinavica. 2025;104:763–73.
Google ScholarÂ
Lycke KD, Kahlert J, Eriksen DO, Omann C, Pedersen LH, Sundtoft I, et al. Preterm birth following active surveillance vs loop excision for cervical intraepithelial neoplasia grade 2. JAMA Netw Open. 2024;7:e242309.
Google ScholarÂ
Rebolj M, Rimmer J, Denton K, Tidy J, Mathews C, Ellis K, et al. Primary cervical screening with high risk human papillomavirus testing: Observational study. BMJ (Online). 2019;364:l240-l.
Digital N. Cervical Screening Programme, England – 2022-2023 [NS]. online2024.

