A retrospective study of 588 patients with atypical glandular cells, not otherwise specified (AGC-NOS), suggests that the phylogenetic clade of an infecting high-risk HPV type, together with patient age and infection multiplicity, can stratify the risk of precancerous or worse lesions. The research, conducted at the International Peace Maternal and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, was published in Diagnostic Pathology and is presented as preliminary evidence pending external validation.
The new analysis set out to characterize age, HPV clade distribution and multiple infections in this population, and to build a refined risk prediction model.
The researchers reviewed records from January 2019 to December 2023. All 588 patients had undergone liquid-based cytology and testing for 14 high-risk HPV genotypes, followed by histopathologic evaluation. Precancerous or worse lesions were identified in 9.5% of patients (56 of 588), and the overall high-risk HPV positivity rate was 17.7% (104 of 588).
The Alpha-9 and Alpha-7 clades were significantly enriched among patients who had outcome lesions compared with those who did not: 19.6% versus 8.3% for Alpha-9, and 17.9% versus 1.5% for Alpha-7.
In multivariable analysis, Alpha-7 emerged as the strongest independent predictor, with an odds ratio of 20.43 (95% confidence interval: 7.22–60.07). Alpha-9 carried an odds ratio of 3.41 (95% CI: 1.43–7.57), and each additional year of age raised the odds by a factor of 1.04 (95% CI: 1.01–1.07). The model also incorporated infection multiplicity and AGC subtype.
Performance was moderate rather than definitive. The model showed acceptable discrimination, with an area under the curve of 0.74 (95% CI: 0.66–0.82), and good calibration. Discrimination of 0.74 indicates meaningful but imperfect separation of patients who develop lesions from those who do not, leaving room for refinement.
When patients were sorted into risk groups, observed lesion rates rose in a graded fashion: 4.5% (8 of 176) in the low-risk group, 8.2% (30 of 364) in the intermediate-risk group, and 37.5% (18 of 48) in the high-risk group, with a P for trend of 6.7 × 10⁻⁸. This gradient suggests the model captures real differences in risk across the cohort.
The authors concluded that a model incorporating HPV phylogenetic clades, age, infection multiplicity and AGC subtype provided preliminary evidence of potential value for risk stratification in AGC-NOS, with the Alpha-7 clade as the strongest independent predictor. They emphasized that pending external validation, this approach may support more individualized management of patients with AGC-NOS.
Several limitations frame these findings. The study was retrospective and single-center, and its results derive from one hospital’s patient population over a five-year period. The reported odds ratios and risk-group rates describe associations within this cohort and do not by themselves establish that clade testing improves clinical outcomes. The authors themselves flag external validation as a prerequisite before the model could inform practice.
Within those limits, the work adds a specific technical angle to HPV-based cervical cancer risk assessment: rather than treating all high-risk HPV infections alike, it distinguishes between phylogenetic clades, finding that Alpha-7 types carried a markedly higher association with precancerous or worse lesions in this AGC-NOS population. If validated in independent cohorts, such clade-level information could help identify which patients with this ambiguous cytological result warrant the closest follow-up.
Subject of Research: Risk prediction modeling for high-grade cervical lesions in patients with atypical glandular cells using HPV phylogenetic clades
Article Title: Risk stratification of high-grade lesions in atypical glandular cells, not otherwise specified: a refined model incorporating HPV phylogenetic clades and multiple HPV infection
Article References: Li, J., Zou, Q., Wang, Y., Zhou, X., Pan, L., Lin, W., & Zhou, F. (2026). Risk stratification of high-grade lesions in atypical glandular cells, not otherwise specified: a refined model incorporating HPV phylogenetic clades and multiple HPV infection. Diagnostic Pathology. https://doi.org/10.1186/s13000-026-01858-9
Image Credits: AI Generated
DOI: 10.1186/s13000-026-01858-9
Keywords: AGC-NOS, HPV, Alpha-7 clade, Alpha-9 clade, risk stratification, cervical cytology, precancerous lesions, liquid-based cytology, hrHPV testing, retrospective study, Diagnostic Pathology, Risk
News Source: Ophelia Keating. (October 29, 2026). HPV Clades and Age Sharpen Risk Prediction for High-Grade Lesions in AGC-NOS. Scienmag.
