Association and Effectiveness of PAX1 Methylation and HPV Viral Load for the Detection of Cervical High-Grade Squamous Intraepithelial Lesion

Abstract

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+.

PAX1/JAM3 Methylation and HPV Viral Load in Women with Persistent HPV Infection

“…Although some studies [19,38] have explored the correlation between HPV VL and disease severity, other findings proposed that HPV VL levels did not show any significant association with type-specific hrHPV persistence or subsequent development of cervical intraepithelial neoplasia, especially within women under 30 with normal cytology [39]. It seems that HPV16/18 VL plays a crucial role in contributing to HPV persistency [40] and was positively correlated with the grade of cervical lesions (CIN3 > CIN2 > CIN1, p < 0.05) [30]. However, it has also been found that lower HPV VL and viral genome integration predict the persistence of HPV16 but not the progression of a persistent HPV16 infection to CIN3+ in women with normal cytology [41].…”

“…Normalization of HPV type-specific VLs was executed using the formula: VL = log10[(CnHPV/CnTOP3) × 10,000] copies/10,000 cells, where CnHPV represents the quantity of HPV DNA and CnTOP3 denotes the number of human cells. The experimental protocol closely followed the procedures outlined in previous reports [30,34].…”

“…Previous studies have primarily focused on the correlation between methylation, HPV VL, and cervical precancerous lesions [30]. However, there is relatively limited research on the correlation of these two biomarkers in populations with early stage of persistent HPV infection before the occurrence of cervical lesions.…”

Reactivation of methylation‐silenced PAX1 inhibits cervical cancer proliferation and migration via the WNT/TIMELESS pathway

“…Additionally, studies have demonstrated that the PAX1m level can accurately distinguish between high‐grade cervical intraepithelial neoplasia (CIN) lesions and CC, particularly in CC screening or triage testing of mildly abnormal cytology. Moreover, PAX1m has been indicated to reduce the referral rate to colposcopy via triage of high‐grade squamous intraepithelial lesions 9 and contributes to predicting the pathological upgrade of CIN before cold knife conization 10 . Recent studies have also shown that PAX1m levels may predict the efficacy of chemoradiotherapy in CC patients 11 .…”