Molecular biology of papillomaviruses in pre-malignant cervical infection

Abstract

The samples analysed were cervical scrapes taken at a colposcopy clinic. HPVs were detected in 90% of specimens with low grade lesions (CIN 1) and 100% of high grade lesions (CIN3). HPV types commonly found in cancer (high risk types 16, 18, 31, and 45) were detected in 80% of specimens with CIN 3, but only 40% of specimens with CIN 1). Moderate risk HPV types (including types 33, 35, 39, and 56) were detected in 19% of CIN 3 and 34% of CIN 1 and low risk HPV types (e.g. 6, 11, 42, and 66) were detected in 11% of CIN 1, but less than 1% of samples with CIN 3. No positive predictive value was found using viral load as an indicator of disease severity. Cervical infection with herpesviruses was found more often in women with progressing CIN, but there was no correlation with cervical cytokine or chemokine production and grade of CIN. However, mixed HPV infections increased in incidence with increasing lesion severity.

The most commonly isolated HPV type in all grades of CIN was HPV-16. Transcripts coding for the oncogenic proteins, E6 and E7, were more commonly detected in high grade lesion severity.

The production of transcripts for host proteins implicated in uncontrolled cellular replication was investigated. Survivin transcripts were present in 30% of CIN samples. Interestingly, samples not expressing survivin transcripts contained higher levels of HPV-16 E6 transcripts. A polymorphism in intron 6 of the p53 gene was linked to the presence of CIN. However, this polymorphism only accounted for susceptibility to CIN in a minor group of women.

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