Background: PAX1 methylation (PAX1m) and HPV viral load (VL) have been reported to detect cervical high-grade squamous intraepithelial lesions (HSIL), but the relationship between them is unclear. This study aimed to evaluate the correlation between HPV VL and PAX1m and its effectiveness in predicting cervical lesions. (2) Methods: A total of 476 women referred to colposcopy for abnormal cervical screening at the Peking University People’s Hospital between November 2020 and November 2021 were enrolled. PAX1m and HPV VL were determined by QMSP and BMRT-HPV reports type-specific VL/10,000 cells, respectively. (3) Results: PAX1m was significantly increased in HSIL, especially in cervical cancer, but there was no significant difference between cervical intraepithelial neoplasms 1(CIN1) and CIN2. However, HPV VL significantly differed between CIN1 and CIN2 but not between CIN3 and cervical cancer. In general, PAX1m positively correlated with all hrHPV VL, mainly in the HPV16/18 VL (p < 0.001), but had no relationship with the other 12 types of hrHPV VL. PAX1m had the highest specificity in diagnosing CIN2+, followed by HPV16/18 VL, which are higher than cytology ≥ASCUS. (4) Conclusions: Hypermethylation of PAX1 is associated with high HPV VL, especially HPV16/18, and both present advantageous specificity in detecting CIN2+.
ObjectiveTo explore the ability of PAX1 methylation (PAX1m) to predict the pathological upgrade of cervical intraepithelial neoplasia (CIN) before cold knife conization (CKC).MethodsA total of 218 women that underwent colposcopy-directed biopsy (CDB) pathology for the confirmation of CIN2 and CIN3 between December 2020 to September 2021 were enrolled in this study. The methylation levels of PAX1 (ΔCpPAX1) were determined by quantitative methylation-specific polymerase chain reaction (qMSP). Receiver operating characteristic curve was used to identify the optimal cut-off value of ΔCpPAX1 for predicting the pathological upgrade of disease.ResultsIn the CDB-confirmed CIN2 group, 36% of CIN2 was found to have pathologically upgraded to CIN3 and 30% regressed to low-grade squamous intraepithelial lesion (LSIL) and below, and none of CIN2 upgraded to early-stage cervical cancer (ESCC) after CKC. In the CDB-confirmed CIN3 group, 19.5% (23/118) of CDB-confirmed CIN3 were pathologically upgraded to ESCC after CKC. Regardless of CIN2 or CIN3, the ΔCpPAX1 level of women with upgraded pathology after CKC was significantly lower than that of women with degraded pathology. The optimal △CpPAX1 cut-off value in predicting CIN3 to be upgraded to ESCC after CKC was 6.360 and the area under the curve (AUC) was 0.814, with similar sensitivity (78.3%) and higher specificity (84.2%) than cytology≥LSIL (Se:78.3%;Sp:58.9%) and HPV16/18 positive (Se:73.9%;Sp:46.3%) patients.ConclusionsPAX1m could be a promising auxiliary marker in predicting the pathological upgrade of CIN before CKC. We found that if the △Cp PAX1 cut-off value is lower than 6.360, it is highly suggestive of invasive cervical cancer.
Objective. This study evaluated the distribution of vaginal microbiota dysbiosis and the association with HPV viral load test in high-risk HPV-positive women before and after 50 years old. Methods. For this cross-sectional study, 388 HPV-positive women prior to referral to colposcopy in Peking University Peoples’ Hospital were included and classified as younger than 50 years ( n = 307 ) and aged 50 years or older ( n = 81 ), midvagina bacterial community composition was characterized by FlashDetect™ MAX vaginal microbe detection kit, and BMRT-HPV reported type-specific viral loads/10,000 cells. Results. The community state type (CST) IV was the most common CST occurring in 148 women (38.1%). The proportion of CST IV in those aged 50 years or older was significantly higher than those younger than 50 years (women) (66.7% vs. 30.6%); the difference was statistically significant (<0.001). CST distribution has no statistical difference in different grades of cervical lesion, regardless of the age ( p = 0.238 and 0.263). However, the women with high-grade cervical lesion presented a more complicated trend and the abundance of vaginal microbiota dysbiosis than low-grade lesion. HPV16/18 viral load was found to be significantly higher in CST III and CST IV than CST I/II/V ( p < 0.05 )in women younger than 50 years. Conclusions. In women younger than 50 years, higher HPV16/18 load was more closely associated with CST IV; however, it had no significant correlation in women aged 50 years or older.
The relationship between the thickness of the epithelium and the colposcopic diagnosis is controversial. The present study was conducted to determine whether colposcopic underdiagnosis of cervical intraepithelial neoplasia (CIN) is associated with thin high-grade squamous intraepithelial lesions (HSILs) of the cervix. A total of 136 cases of HSIL verified by pathological biopsy at Peking University People's Hospital between June and October 2021 were retrospectively analyzed; 79 cases were CIN2 and 57 cases were CIN3. The number and thickness of epithelial layers were analyzed using colposcopic impressions. In the low-grade colposcopic impression group, the number of epithelial layers (12.8±4.2 vs. 17.8±4.2) and epithelial thickness (105.2±41.9 µm vs. 150.3±50.0 µm) of CIN2 lesions were significantly lower compared with the high-grade colposcopic impression group; however, the differences for CIN3 were not statistically significant. CIN2 lesions had significantly fewer (12.8±4.2 vs. 17.2±5.4) and thinner (105.2±41.9 µm vs. 140.4±48.6 µm) epithelial layers than CIN3 lesions in the low-grade colposcopic impression groups. In the high-grade colposcopic impression group, however, there were no significant differences in the number or thickness of epithelial layers between CIN2 and CIN3. In 12 cases of thin HSILs, 91.6% of the colposcopic impressions were low-grade. Thin HSILs are likely associated with underdiagnosed colposcopic findings, particularly for CIN2. Thin HSILs usually present with small to minute lesions and lack the typical colposcopic appearance of classic HSIL, which may help to explain why thin HSILs are easily underestimated under colposcopy.
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