BJOG : an international journal of obstetrics and gynaecology · 2026
SOX1/PAX1 Methylation for Triage of HPV-Positive Women in Cervical Cancer Screening: A Cohort Study.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Xie Hongyu, Li Junyan, Huang Huiru, Emmanuel Ansong, Wang Hui, Lu Weiguo, Li Xiao
Аннотация
OBJECTIVE: To establish a better triage strategy using SOX1/PAX1 methylation detection for high-risk HPV (hrHPV)-positive women than cytology.
DESIGN: A cohort study.
SETTING: Population-based cervical cancer (CC) screening cohort.
POPULATION: A total of 5684 women were enrolled.
METHODS: SOX1/PAX1 methylation was detected by quantitative methylation-specific PCR using cytologic residue from hrHPV-positive women at baseline in a 3-year CC screening cohort. Risk stratification ability was evaluated by the immediate and cumulative cervical intraepithelial neoplasia (CIN) grade 2/3 or worse (CIN2+/3+) risks.
MAIN OUTCOME MEASURES: CIN3+ and CIN2+.
RESULTS: At baseline, 682 hrHPV-positive women were included with 63 CIN2+ and 39 CIN3+. Over 3 years, 109 CIN2+ and 62 CIN3+ were detected. Methylation demonstrated better risk stratification than cytology among hrHPV-positive women. When compared with current practice triage strategy (Strategy A), post hoc re-triage analysis showed that methylation triage for all hrHPV-positive women (Strategy C) significantly increased sensitivity (97.44%/83.87% vs. 84.62%/64.52%, p = 0.0476/0.014), specificity (83.36%/85.00% vs. 73.41%/73.55%, p = < 0.001/< 0.001), positive predictive value (26.21%/35.86% vs. 16.18%/19.61%, p = 0.022/0.001), and negative predictive value (99.81%/98.14% vs. 98.74%/95.40%, p = 0.040/0.012) in detecting immediate and 3-year cumulative CIN3+. Similar improvements were observed for methylation triaged for HR12-positive (Strategy B) and for combined HPV and cytology primary screening (Strategy D). More importantly, all methylation-based triage strategies reduced colposcopies and postponed follow-up intervals compared to Strategy A over the 3-year period of CC screening.
CONCLUSION: SOX1/PAX1 methylation showed better risk stratification compared with cytology and enabled more efficient management of HPV-positive women, though external validation and head-to-head comparisons with other triage methods are needed.
DESIGN: A cohort study.
SETTING: Population-based cervical cancer (CC) screening cohort.
POPULATION: A total of 5684 women were enrolled.
METHODS: SOX1/PAX1 methylation was detected by quantitative methylation-specific PCR using cytologic residue from hrHPV-positive women at baseline in a 3-year CC screening cohort. Risk stratification ability was evaluated by the immediate and cumulative cervical intraepithelial neoplasia (CIN) grade 2/3 or worse (CIN2+/3+) risks.
MAIN OUTCOME MEASURES: CIN3+ and CIN2+.
RESULTS: At baseline, 682 hrHPV-positive women were included with 63 CIN2+ and 39 CIN3+. Over 3 years, 109 CIN2+ and 62 CIN3+ were detected. Methylation demonstrated better risk stratification than cytology among hrHPV-positive women. When compared with current practice triage strategy (Strategy A), post hoc re-triage analysis showed that methylation triage for all hrHPV-positive women (Strategy C) significantly increased sensitivity (97.44%/83.87% vs. 84.62%/64.52%, p = 0.0476/0.014), specificity (83.36%/85.00% vs. 73.41%/73.55%, p = < 0.001/< 0.001), positive predictive value (26.21%/35.86% vs. 16.18%/19.61%, p = 0.022/0.001), and negative predictive value (99.81%/98.14% vs. 98.74%/95.40%, p = 0.040/0.012) in detecting immediate and 3-year cumulative CIN3+. Similar improvements were observed for methylation triaged for HR12-positive (Strategy B) and for combined HPV and cytology primary screening (Strategy D). More importantly, all methylation-based triage strategies reduced colposcopies and postponed follow-up intervals compared to Strategy A over the 3-year period of CC screening.
CONCLUSION: SOX1/PAX1 methylation showed better risk stratification compared with cytology and enabled more efficient management of HPV-positive women, though external validation and head-to-head comparisons with other triage methods are needed.
Предметные рубрики MeSH
Prospective StudiesEarly Detection of CancerHumansFemaleYoung AdultAdultMiddle AgedAgedChinaUterine Cervical NeoplasmsSOXB1 Transcription FactorsPaired Box Transcription FactorsTriageDNA MethylationPolymerase Chain ReactionPredictive Value of TestsHuman Papillomavirus VirusesUterine Cervical Dysplasia