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Improving Efficiency in Dutch Cervical Screening by Genotyping: An Analysis of Real World Program Data.
Ellen M G Olthof1, Adriaan J C van den Brule2, Willem J G Melchers3
1Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands.
Journal of Medical Virology
|December 10, 2025
Summary
Genotype-specific human papillomavirus (HPV) testing improves cervical cancer screening. HPV16 and HPV18 infections significantly increase risks for high-grade cervical intraepithelial neoplasia (CIN) and cancer, while reducing unnecessary referrals.
Area of Science:
- Gynecology
- Oncology
- Virology
Background:
- Cervical screening efficiency can be improved by stratifying risk based on high-risk human papillomavirus (hrHPV) genotypes.
- Cytology-positive (ASCUS+) women require accurate risk assessment for cervical intraepithelial neoplasia (CIN) and cancer.
Purpose of the Study:
- To evaluate the risks of CIN, cancer, and unnecessary referrals associated with specific hrHPV genotypes (HPV16, HPV18, hrHPV-other) in cytology-positive women.
- To assess the utility of genotype-specific risk stratification for enhancing cervical screening efficiency.
Main Methods:
- Analysis of data from hrHPV-positive/ASCUS-positive women in the Dutch cervical screening program (January 2017-March 2018).
- Logistic regression models were used to evaluate risks for CIN2+/3+, cancer, and unnecessary referrals by hrHPV genotype, adjusted for age and other factors.
- Stratification by age (<50 and ≥50 years) was performed.
Main Results:
- HPV16-positive women had 3.7 and 4.6 times higher risks of CIN2+ and CIN3+, respectively, compared to hrHPV-other.
- HPV18-positive women showed 1.6 and 1.9 times higher risks of CIN2+ and CIN3+, respectively.
- Cervical cancer risk was significantly elevated (approx. tenfold) for both HPV16 and HPV18 infections.
- Women with HPV16 and HPV18 had substantially lower risks of unnecessary referrals compared to hrHPV-other infections.
Conclusions:
- HPV16 and HPV18 genotypes are associated with significantly higher risks of high-grade CIN and cervical cancer.
- Genotype-specific risk assessment, particularly identifying HPV16 and HPV18, can reduce unnecessary referrals in cervical screening.
- Implementing genotype-based colposcopy referrals can enhance the overall efficiency of cervical screening programs.

