Background: The human papillomavirus (HPV) is recognized as the main etiological agent of cervical cancer. High risk HPV types are responsible for almost 90% of cervical cancers worldwide. HPV16 is the most frequent of these high risk types being found in more than 60% of cervical tumors, followed by HPV18 which is responsible for about 15% of these tumors.
Methods: In this work we have studied sequence variations within the open reading frames (ORFs) L1 and E6 of five HPV18 isolates derived from Tunisian women with different grades of cervical lesions. Viral DNA was detected by PCR using consensus primers for L1. HPV typing was performed by HPV type-specific PCR in ORF E6 and by automated sequencing of amplicons using Big Dye Terminators technology. The L1 and E6 sequences obtained for each isolate were aligned against reference HPV18 sequences representing the main variant strains of the major geographical regions of the world.
Results: All five isolates were variants of the European lineages. They all showed hitherto undescribed mutations in L1: a transversion A6630T and a transition C6631T in four of the isolates and a G to A transition (G6731A) in all five. No new mutations were found in ORF E6 amplicons. Analysis of the translation products showed that A6630T and C6631T were significant, leading to amino acid changes T340L and N341R, respectively. The G to A transition was synonymous.
Conclusion: The mutations detected in this study seem to be characteristic of HPV18 strains circulating in Tunisia and their effects on virus biology and pathogenicity will be discussed.