MOLECULAR VARIANT ANALYSIS OF PERSISTENT HPV-52 INFECTION IN HIV-INFECTED WOMEN

J Aho, C Hankins, F Lang, The Canadian Women’s HIV Study Group, F Coutlée
Centre Hospitalier de l’Université de Montréal, Montreal University, and Department of Epidemiology and Biostatistics, McGill University, Montreal, Quebec

Background: Non-prototypic variants of human papillomavirus (HPV) type 16 are associated with persistent infection and high-grade cervical lesions. The role of molecular variants from other HPV types has not been well documented.
Objectives: To describe the genetic polymorphism of HPV-52 and assess the association between molecular variants and persistent HPV infection in women at risk or infected with HIV.
Methods: Consecutive cervicovaginal lavages obtained at 6-month intervals were tested for HPV-52. One isolate from each HPV-52-infected woman was tested for variant analysis by PCR-sequencing of the long control region (LCR), E6 and E7 genes. Variants were classified according to the HPV-52 prototype sequence. Results: 112 (13.9%) of 807 women were infected by HPV-52. Ninety (18%) of 484 HIV+ women and 22 (7%) of 323 HIV– women were infected by HPV-52 (p<0.001). Of these, 43 women and 14 women had definitive persistent and transient infections, respectively. 45 mutations in the LCR defined 27 HPV-52 variants. The most frequent mutation was at nucleotide 7624 (T=>C). The most frequent variant was the prototype (43/112, 38.3%). Deletions were found more frequently with HPV-52 than HPV-16 (37 of 112 isolates versus 0 of 144, p<0.01). 19 LCR variants had more than 2 mutations. Non-prototype-like variants were found more frequently in persistent infection (28 (65.1%) of 43 women) than transient infections (4 (28.6%) of 14 women; p=0.03). 17 variants and 9 variants were found in E6 and E7 genes, respectively. In E6, 7 mutations were significant resulting in a clustering of modifications in E6 from amino acids 92 to 94. 12 mutations were significant in E7 and found in amino acids 52 to 64 of E7.
Conclusions: The genetic polymorphism of HPV-52 differed from that of HPV-16. Persistent HPV-52 infection was associated in our population with non-prototype-like molecular variants.