Persistent infection with high-risk HPV is the main cause of cervical cancer. There have been numerous reports on the relationship between high HPV viral load and DNA methylation with high-grade cervical lesions. However, the changes in persistent HPV infection, epigenetics, and viral load in low-grade cervical lesions and non-lesions remain unclear.

Recently, a study titled "PAX1/JAM3 Methylation and HPV Viral Load in Women with Persistent HPV Infection" was published in the journal Cancers (IF: 5.2). The research, led by Professor Lihui Wei's team from Peking University People's Hospital, with Professors Mingzhu Li and Chao Zhao as the first authors, provides an in-depth analysis of the clinical significance of JAM3/PAX1 gene methylation and viral load in persistent HPV infection.

Conclusion:

The correlation analysis revealed a significant and highly correlated relationship between the methylation of PAX1 and JAM3, particularly exhibiting significant methylation of JAM3 among women with infections persisting for over three years. HPV infection persisting for more than 3 years is more likely to be associated with vaginal lesions, and HPV viral load (VL) could be used as an indicative biomarker for concurrent cervical–vaginal lesions.

Objective:

This study aims to investigate the correlation between persistent HPV infection without high-grade cervical lesions and the methylation of PAX1/JAM3 genes, as well as HPV viral load.

Methodology:

A total of 231 females diagnosed with persistent HPV infection and pathologically confirmed absence of high-grade cervical lesions were selected from the Colposcopy Outpatient Clinic of Peking University People’s Hospital, from March 2023 to December 2023. They were categorized into two groups based on the duration of HPV infection: the HPV persistent less than 3 years group and the more than 3 years group. PAX1/JAM3 methylation and HPV VL were determined by real-time PCR and BioPerfectus Multiplex Real-Time (BMRT)-HPV reports type-specific VL/10,000 cells, respectively.

Research Findings:

1. The average age of HPV infection was higher with infections lasting over 3 years than with infections lasting under 3 years (48.9 vs. 45.1), with a statistically significant difference.

2. The top 7 persistent positive HPV genotypes were HPV16 (24.6%), HPV52 (23.5%), HPV58 (15.5%), HPV31 (12.8%), HPV56 (10.7%), HPV39 (9.6%), and HPV18 (8.6%).

3. The methylation levels of JAM3 and PAX1 were significantly higher in individuals with HPV infection persisting for more than 3 years compared to those with less than 3 years, with a statistically significant difference (p < 0.05). JAM3 methylation shows a greater advantage in determining persistent infection. High methylation levels of both JAM3 and PAX1 can serve as cumulative evidence of the duration of persistent HPV infection before the onset of precancerous lesions.

4. Among 187 high-risk HPV-positive samples with an infection duration of ≥3 years, there was a statistically significant correlation between JAM3 and total HPV VL (p = 0.037) but no significant correlation with genotypes.

The relationship between HPV−VL and methylation tests.

5. Women with persistent HPV infection for more than 3 years had a higher incidence of vaginal intraepithelial neoplasia (VaIN) (18.7% vs. 9.0%). Analysis of 28 cases with concurrent vaginal lesions showed significant statistical differences in total HPV load and non-HPV16/18 types between patients with and without vaginal lesions. HPV load can serve as an indicative biomarker for concurrent cervical-vaginal lesions, especially in cases of high-risk non-HPV16/18 infections.

Dot plot of different tests in pathology normal/CIN1 and combined vaginal lesions.

Overall, the relationship between HPV viral load, persistent HPV infection, and carcinogenicity remains to be further explored. In particular, HPV infections persisting for more than 3 years are more likely to be associated with vaginal lesions. HPV viral load could be used as an indicative biomarker for concurrent cervical-vaginal lesions.

Reference:

Li M, Zhao C, Zhang X, Li J, Zhao Y, Zhang W, Ren L, Wei L. PAX1/JAM3 Methylation and HPV Viral Load in Women with Persistent HPV Infection. Cancers (Basel). 2024 Apr 7;16(7):1430. doi: 10.3390/cancers16071430. PMID: 38611108; PMCID: PMC11010937.