Genotyping human papillomavirus type 16 isolates from persistently infected promiscuous individuals and cervical neoplasia patients

Abstract

Nucleotide sequence variation in the noncoding region of the genome of human papillomavirus type 16 (HPV16) was determined by direct sequencing and single-strand conformation polymorphism analysis of DNA fragments amplified by PCR. Individuals of diverse sexual promiscuity and/or cervicopathology were studied. In a group of 14 healthy, monogamous HPV16-positive females, only two HPV16 sequence variants could be documented. Among 17 females and 3 males with multiple sex partners and living in the same geographical region, nine sequence variants were found, whereas among 7 patients with cervical neoplasia from another region, five variants were detected. Although numbers are limited, in the group of individuals at high risk of acquiring a sexually transmitted disease or with cervical neoplasia, a larger number of HPV16 sequence variants was encountered (two types among 14 individuals versus nine types among 20; Fisher's exact test, P ‫؍‬ 0.07). Seven of the individuals were sampled repeatedly over time. For these persistently infected women, no differences in HPV16 sequences were detected, irrespective of promiscuity, and persistence of a single viral variant, spread over multiple anatomic sites, for more than 2 years could be demonstrated. This indicates that viral persistence may be a common feature and that successful superinfection with a new variant may be rare, despite a potentially high frequency of viral reinoculation.

Human papillomavirus type 16 sequence variants: identification by E6 and L1 lineage-specific hybridization

“…If mixed HPV-16 variant infections are, in fact, rare, this observation would potentially support a model for immunological protection by one HPV-16 variant infection from a subsequent HPV-16 infection. As discussed by other investigators, the establishment of a persistent infection in which a single HPV-16 variant predominates over time may similarly provide indirect support for such a model (59,67). This suggestion contrasts with the finding that HPV infections are commonly observed as mixed infections with multiple HPV types (2,3,22,39,66).…”

Detection of Human Papillomavirus Type 16 DNA in Consecutive Genital Samples Does Not Always Represent Persistent Infection as Determined by Molecular Variant Analysis

“…On this basis, HPV-16 can be classified into more than 40 variants (6,20,25,41) which have a less than 2% variation in DNA sequence (33). Molecular variant analysis of HPV-16 isolates allows us to distinguish reinfection from persistence (11,32). Sequence analysis of hypervariable regions of the HPV genome (11) remains the gold standard method for molecular variant analysis.…”

“…However, single-strand conformation polymorphism (SSCP) analysis is an alternative to sequencing for this purpose (38). Only one group has compared the value of HPV-16 variant analysis of PCR-SSCP patterns with that of PCR-sequencing of clinical specimens (32). A simplified dot blot analysis to classify HPV-16 isolates into the major HPV-16 lineages has also been described (35).…”

Assessment of the serological relatedness of genital human papillomaviruses by hemagglutination inhibition

“…The absence of serological cross-reactivity presumably helps an infecting HPV to evade a prior host humoral immune response directed against other HPV types, a feature that may account in part for the multiplicity of HPV genotypes. Superinfection with a new variant of HPV-16 is rare despite a probability in promiscuous individuals, suggesting that the immune response generated by infected individuals offers some degree of protection from variants (30). To investigate the possibility that this protection is mediated by neutralizing antibodies, antisera to two relatively divergent HPV-16 variants from Germany and Zaire (114/K and Z-1194, respectively), which differ in seven residues in L1, were tested by the HAI assay.…”