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Lorich et al (2009) suggested that, "[i]f the detection of methylated HPV E6 and E7 genes is shown to reliably and accurately identify high-grade CIN, the assay may be used for triage of low-grade lesions as well as disease screening". This study evaluated the methylation status of HPV16 and HPV18 E6, E7, and L1 genes in cells of high-grade lesions and compared it with that of normal cervix and neoplastic, normal, and precancerous lesions of any grade a must show continuous expression of HPV E6 and E7 for L1 gene analyses. Methylation frequencies were analyzed using methylation-specific PCR. All high-grade cervical neoplasms had a methylated HPV16 E6 gene and/or E7 gene, but they had a different methylation frequency than that of HPV16 and/or HPV18 E6 and E7 gene methylation. Upregulation of HPV16 E6 and E7 gene methylation frequencies in cervical neoplasia increased with the degree of neoplasia. The data indicate that in cervical neoplasia methylation of high-risk HPV E6 and E7 genes is an early phenomenon, and that E6/E7 gene methylation may be used to triage cervical lesions for biopsy. A low-grade screen with follow-up of methylated high-risk HPV E6 and E7 gene-positive cytology may be a useful triage method for identification of high-grade lesions needing biopsy. However, more evidence on the clinical applicability and the correct threshold value for HPV E6 and E7 gene methylation frequencies in the triage of low-grade lesions are required. The methylation rate in HPV-negative normal cervices may be an indication of general spontaneous methylation and is likely not related to cervical neoplasia formation. Additional studies should be conducted to resolve these issues". d2c66b5586

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