MOLECULAR EPIDEMIOLOGY AND SOME FACTORS ASSOCIATED WITH GENITAL HUMAN PAPILLOMAVIRUS INFECTION AMONG WOMEN IN OYO STATE, NIGERIA

Abstract

Genital Human Papillomavirus (HPV) infection is a well-established causative agent of cervical cancer; a major cancer in most developing countries.Persistent infection with high-risk HPV, especially types 16 and 18 have been associated with cervical cancer. Two HPV vaccines (Cervarix and Gardasil) are currently available in Nigeria, targeting two (16 and 18) and four (6, 11, 16 and 18) types, respectively. However, the distribution of HPV types varies greatly across geographical regions with little information on the circulating types among Nigerian women, thus raising concerns about the effectiveness of the available vaccines in the country. This study was therefore designed to determine the circulating HPV types among women in Oyo State, Nigeria and identify some factors associated with the infection. A total of 295 endocervical swab samples were collected from consenting women attending routine cervical cancer screening, STI clinics and community-based outreach programme. The participants were enrolled from University College Hospital, Ibadan; Baptist Medical Centre, Saki and during an outreach in Molete community, Ibadan.Structured questionnaire was used to capture demographic, medical information and sexual history.Genomic DNA was extracted from samples using commercial extraction reagents. The presence of HPV was detected by PCR using two sets of consensus primers targeting the L1 and E6/E7 genes. Six pairs of HPV type-specific primers (16, 18, 31, 33, 35 and 6/11) were then used to genotype the HPV isolates in a nested PCR. Samples not identified by the primers used were sequenced and typed by phylogenetic analysis. Data were analysed using Chi-square at α0.05. Fifty five (18.6%) individuals were positive for HPV infection. Primers targeting E6/E7 region detected more HPV infections (17.3%) than those targeting L1 region (9.2%). Five HPV types were detected using type-specific primers (HPV 16, 18, 31, 33 and 35), while 14 HPV types (HPV 6, 16, 18, 31, 35, 42, 43, 44, 52, 58, 66, 74, 81, 86) were identified by sequencing. In all, 15 HPV types were detected with HPV 31 being the most predominant (32.8%), followed by HPV 35 (17.2%) and HPV 16 (15.5%). About 21.0% of individuals had dual infections while high-risk HPV genotypes were found among 86.2% of HPV-positive individuals. Highest nucleotide substitutions (n=32) were found in HPV 44 genotype while the only HPV 74 isolate had three nucleotide (CCT) insertionsat E7 gene that translated into amino acid proline. Some factors including divorce (p=0.019), illiteracy (p=0.003), polygamy(p=0.027), unemployment (p=0.023), low income earnings (p=0.018), younger age (<18years)at sexual debut (p=0.039) and passive smoking (p=0.017) were associated with HPV infection. Multiple Human Papillomavirus types co-circulated in Oyo State, Nigeria. Most of the circulating Human Papillomavirus are high-risk type with type 31 being the most predominant. Although the implication of the rare HPV 74 with proline insertion detected for the first time in Nigeria is unknown, it may have effect on the transformation potential of the virus. Primers targeting E6/E7 region may be more appropriate for the detection of Human Papillomavirus circulating in Oyo State, Nigeria.