Persistent infection with high-risk HPV genotypes is highly associated with the development of cervical cancer. HPV58 is a member of the HPV16-related alpha9 family and accounts for approximately 2% of all cervical cancer cases worldwide. Genetic variants of HPV58 have been classified into four major lineages, A, B, C and D and seven sub-lineages A1, A2, A3, B1, B2, D1 and D2, the distribution of which varies by geographical region. Lineage A predominates in all regions except in Africa, where lineages A and C are found in comparable proportions.
The aim of this study was to evaluate the potential influence of common HPV58 L1 and L2 polymorphisms on capsid protein recognition by antibodies elicited by natural infection.
HPV58 L1L2 pseudoviruses (PsVs) representing the eight major L1 and L2 variant lineages (A1, A2, A3, B1, B2, C, D1 and D2) were generated. Paired serum and DNA samples collected from women following a diagnosis of ASCUS or LSIL were tested for the presence of neutralizing antibodies against HPV58. HPV58 DNA positive samples from patients with evidence of seroconversion against HPV58 were subjected to fragment sequencing to identify their lineage variant status.
Among the 216 serum samples tested, 31 were seropositive against all HPV58 variants with the exception of the C variant. One serum sample was positive for HPV58 C variant, but did not recognise any other variants. Out of 32 seroconverted individuals, 21 (65%) were also DNA positive against HPV58 of which 19 were infected with HPV58 A2, one with HPV58 C, and one with HPV58 B2. We are currently mapping target specificity of these antibodies by construction of inter-lineage loop swap PsV. These data demonstrate that naturally occurring polymorphisms in the HPV58 capsid proteins affect recognition by antibodies elicited during natural infection and suggest the existence of lineage-level serotypes.