Incidence of Cervical Cancer in HPV-positive Women With Low-grade Cytological Abnormalities

NCT07259616 | Completed

• 1 other identifier: GOCZ
• Study Type: observational
• Target: 46,079
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this observational study is to assess the five-year incidence of histologically confirmed cervical cancer among women who test positive for human papillomavirus (HPV) with low-grade cytological abnormalities, to evaluate whether follow-up intensity could be reduced in women participating in the Dutch population-based cervical cancer screening program who are HPV-positive and have low-grade cytological abnormalities - atypical squamous cells of undetermined significance (ASC-US), atypical glandular cells of endocervical origin (AGC), or low-grade squamous intraepithelial lesions (LSIL). The main questions it aims to answer are: What is the five-year risk of developing cervical cancer in HPV-positive women with low-grade cytological abnormalities? Does the presence of subsequent low-grade cytology affect the five-year risk of cervical cancer in this population? Researchers will compare the risk of cervical cancer in HPV-positive women with low-grade abnormalities to women with stable negative for intraepithelial lesion or malignancy (NILM) cytology, since women with stable NILM are discharged from further follow-up back to the screening programme. This will help evaluate whether follow-up intensity can be reduced in women with low-grade abnormalities.

Conditions

Cervical Intraepithelial Neoplasia; Cervix Uteri Cancer; Human Papilloma Virus; Cervix Carcinoma; Cervix; Intraepithelial Neoplasia

Keywords

Human papilloma virus; Cervical cancer; Low-grade cytological abnormalities; Cervical cancer screening; Retrospective cohort study; Five-year incidence

Outcome Measures

Primary Outcomes (1)

• Five-year incidence cervical cancer

  Incidence of histologically confirmed cervical cancer within the five-year screening interval.

  From enrollment up to 5 years after.

Secondary Outcomes (5)

• Time to diagnosis of cervical carcinoma

  From enrollment up to 5 years after.

• All-cause mortality

  From enrollment up to 5 years after.

• Examination at which the diagnosis cervical carcinoma was established

  Moment of diagnosis of cervical carcinoma from enrollment up to 5 years after.

• Carcinoma subtype

  Moment of diagnosis of cervical carcinoma within 5 years after enrollment.

• Incidence of cervical cancer within 5 years of inclusion stratified by histological diagnosis within three months of enrollment

  From enrollment up to 5 years after.

Study Arms (2)

Cohort low-grade cytological abnormalities

Women who participated in the population-based cervical cancer screening program in the Netherlands between January 2017 and December 2018 who were HPV positive and with cytology results atypical squamous cells of undetermined significance (ASC-US), atypical glandular cells of endocervical origin (AGC), or low-grade squamous intraepithelial lesion (LSIL) according to the Bethesda system.

Cohort HPV positive and no cervical abnormalities

Women who participated in the population-based cervical cancer screening program in the Netherlands between January 2017 and December 2018 who were HPV positive and with a stable cytology result negative for intra-epithelial neoplasia according to the Bethesda system.

Eligibility Criteria

• Gender Eligibility Details: Women/people who have a cervix.
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

This retrospective cohort study included women who participated in the population-based cervical cancer screening program in the Netherlands between January 2017 and December 2018. Eligible participants were HPV-positive and had cytology results categorized as atypical squamous cells of undetermined significance (ASC-US), atypical glandular cells of endocervical origin (AGC), or low-grade squamous intraepithelial lesion (LSIL) or stable negative for intra-epithelial leasion or malignancy (NILM) cytology results after one year according to the Bethesda system.

You may qualify if:

• Women who participated in the cervical cancer screening program in the Netherlands between January 2017 and December 2018, who:
• Tested HPV-positive with cytology results categorized as atypical squamous cells of undetermined significance (ASC-US), atypical glandular cells of endocervical origin (AGC), or low-grade squamous intraepithelial lesion (LSIL) according to the Bethesda system, or
• Were HPV-positive and had stable negative for intra-epithelial leasion or malignancy (NILM) cytology after one year.

You may not qualify if:

• None

Sponsors & Collaborators

• Gynaecologisch Oncologisch Centrum Zuid: lead
• PALGA foundation: collaborator
• Amphia Hospital: collaborator
• Maastricht University: collaborator

Related Publications (14)

• Cervical cancer screening programme. RIVM n.d. https://www.rivm.nl/en/cervical- cancer-screening-programme (accessed June 1, 2025).

  BACKGROUND

• WHO 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 BACKGROUND

• Eramus MC, Palga. Bevolkingsonderzoek Baarmoederhalskanker - Monitor 2017. RIVM 2017.

  BACKGROUND

• The Netherlands: Integraal Kankercentrum Nederland. National Guidelines: CIN, AIS en VAIN (Dutch). Richtlijnendatabase Federatie Medisch Specialisten;Accessed June 2025.

  BACKGROUND

• The Netherlands: Integraal Kankercentrum Nederland. National Guidelines: Cervixcytologie- Codering van de uitslag (Dutch). Richtlijnendatabase Federatie Medisch Specialisten; Accessed June 2025.

  BACKGROUND

• Sharp L, Cotton S, Cruickshank M, Gray NM, Harrild K, Smart L, Walker LG, Little J; TOMBOLA Group. The unintended consequences of cervical screening: distress in women undergoing cytologic surveillance. J Low Genit Tract Dis. 2014 Apr;18(2):142-50. doi: 10.1097/LGT.0b013e31829c97d8.

  PMID: 24270192 BACKGROUND

• Katki HA, Gage JC, Schiffman M, Castle PE, Fetterman B, Poitras NE, Lorey T, Cheung LC, Raine-Bennett T, Kinney WK. Follow-up testing after colposcopy: five-year risk of CIN 2+ after a colposcopic diagnosis of CIN 1 or less. J Low Genit Tract Dis. 2013 Apr;17(5 Suppl 1):S69-77. doi: 10.1097/LGT.0b013e31828543b1.

  PMID: 23519308 BACKGROUND

• Ciavattini A, Serri M, Di Giuseppe J, Liverani CA, Gardella B, Papiccio M, Delli Carpini G, Morini S, Clemente N, Sopracordevole F. Long-term observational approach in women with histological diagnosis of cervical low-grade squamous intraepithelial lesion: an Italian multicentric retrospective cohort study. BMJ Open. 2019 Jul 3;9(7):e024920. doi: 10.1136/bmjopen-2018-024920.

  PMID: 31272971 BACKGROUND

• Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, Schiffman MH, Moreno V, Kurman R, Shah KV. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst. 1995 Jun 7;87(11):796-802. doi: 10.1093/jnci/87.11.796.

  PMID: 7791229 BACKGROUND

• Jansen EEL, Zielonke N, Gini A, Anttila A, Segnan N, Voko Z, Ivanus U, McKee M, de Koning HJ, de Kok IMCM; EU-TOPIA consortium. Effect of organised cervical cancer screening on cervical cancer mortality in Europe: a systematic review. Eur J Cancer. 2020 Mar;127:207-223. doi: 10.1016/j.ejca.2019.12.013. Epub 2020 Jan 21.

  PMID: 31980322 BACKGROUND

• Melnikow J, Henderson JT, Burda BU, Senger CA, Durbin S, Weyrich MS. Screening for Cervical Cancer With High-Risk Human Papillomavirus Testing: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2018 Aug 21;320(7):687-705. doi: 10.1001/jama.2018.10400.

  PMID: 30140883 BACKGROUND

• US Preventive Services Task Force; Curry SJ, Krist AH, Owens DK, Barry MJ, Caughey AB, Davidson KW, Doubeni CA, Epling JW Jr, Kemper AR, Kubik M, Landefeld CS, Mangione CM, Phipps MG, Silverstein M, Simon MA, Tseng CW, Wong JB. Screening for Cervical Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018 Aug 21;320(7):674-686. doi: 10.1001/jama.2018.10897.

  PMID: 30140884 BACKGROUND

• Bruni L, Serrano B, Roura E, Alemany L, Cowan M, Herrero R, Poljak M, Murillo R, Broutet N, Riley LM, de Sanjose S. Cervical cancer screening programmes and age-specific coverage estimates for 202 countries and territories worldwide: a review and synthetic analysis. Lancet Glob Health. 2022 Aug;10(8):e1115-e1127. doi: 10.1016/S2214-109X(22)00241-8.

  PMID: 35839811 BACKGROUND

• Arbyn M, Weiderpass E, Bruni L, de Sanjose S, Saraiya M, Ferlay J, Bray F. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Health. 2020 Feb;8(2):e191-e203. doi: 10.1016/S2214-109X(19)30482-6. Epub 2019 Dec 4.

  PMID: 31812369 BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: September 24, 2025
• First Posted: December 2, 2025
• Study Start: January 1, 2017
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share