Dataset Information

Distribution of high-risk human papillomavirus genotypes among HIV-negative women with and without cervical intraepithelial neoplasia in South Africa.

ABSTRACT:

Objective

Large studies describing the profile of high-risk Human papillomavirus (hrHPV) genotypes among women in sub-Saharan Africa are lacking. Here we describe the prevalence and distribution of hrHPV genotypes among HIV-negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN).

Methods

We report data on 8,050 HIV-negative women, aged 17-65 years, recruited into three sequential studies undertaken in Cape Town, South Africa. Women had no history of previous cervical cancer screening. Cervical samples were tested for hrHPV DNA using the Hybrid Capture 2 (HC2) assay and all positive samples were genotyped using a PCR-based assay (Line Blot). Women underwent colposcopy and biopsy/endocervical curettage to determine CIN status. The prevalence and distribution of specific hrHPV genotypes were examined by age and CIN status.

Results

Overall, 20.7% (95% CI, 19.9-21.6%) of women were hrHPV-positive by HC2, with women with CIN having the highest rates of positivity. Prevalence decreased with increasing age among women without CIN; but, a bimodal age curve was observed among women with CIN. HPV 16 and 35 were the most common hrHPV genotypes in all age and CIN groups. HPV 45 became more frequent among older women with CIN grade 2 or 3 (CIN2,3). Younger women (17-29 years) had more multiple hrHPV genotypes overall and in each cervical disease group than older women (40-65 years).

Conclusion

HPV 16, 35, and 45 were the leading contributors to CIN 2,3. The current HPV vaccines could significantly reduce HPV-related cervical disease; however, next generation vaccines that include HPV 35 and 45 would further reduce cervical disease in this population.

SUBMITTER: McDonald AC

PROVIDER: S-EPMC3435398 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Distribution of high-risk human papillomavirus genotypes among HIV-negative women with and without cervical intraepithelial neoplasia in South Africa.

McDonald Alicia C AC Denny Lynette L Wang Chunhui C Tsai Wei-Yann WY Wright Thomas C TC Kuhn Louise L

PloS one 20120906 9

<h4>Objective</h4>Large studies describing the profile of high-risk Human papillomavirus (hrHPV) genotypes among women in sub-Saharan Africa are lacking. Here we describe the prevalence and distribution of hrHPV genotypes among HIV-negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN).<h4>Methods</h4>We report data on 8,050 HIV-negative women, aged 17-65 years, recruited into three sequential studies undertaken in Cape Town, South Africa. Women had no history ...[more]

PMID: 22970201

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Project description:OBJECTIVE:HIV-positive women are known to be at high-risk of human papillomavirus (HPV) infection and its associated cervical pathology. Here, we describe the prevalence and distribution of HPV genotypes among HIV-positive and -negative women in South Africa, with and without cervical intraepithelial neoplasia (CIN). METHODS:We report data on 1,371 HIV-positive women and 8,050 HIV-negative women, aged 17-65?years, recruited into three sequential studies in Cape Town, South Africa, conducted among women who had no history of cervical cancer screening recruited from the general population. All women were tested for HIV. Cervical samples were tested for high-risk HPV DNA (Hybrid Capture 2) with positive samples tested to determine the specific genotype (Line Blot). CIN status was determined based on colposcopy and biopsy. RESULTS:The HPV prevalence was higher among HIV-positive women (52.4%) than among HIV-negative women (20.8%) overall and in all age groups. Younger women, aged 17-19?years, had the highest HPV prevalence regardless of HIV status. HIV-positive women were more likely to have CIN 2 or 3 than HIV-negative women. HPV 16, 35, and 58 were the most common high-risk HPV types with no major differences in the type distribution by HIV status. HPV 18 was more common in older HIV-positive women (40-65?years) with no or low grade disease, but less common in younger women (17-29?years) with CIN 2 or 3 compared to HIV-negative counterparts (p?<?0.03). Infections with multiple high-risk HPV types were more common in HIV-positive than HIV-negative women, controlling for age and cervical disease status. CONCLUSION:HIV-positive women were more likely to have high-risk HPV than HIV-negative women; but, among those with HPV, the distribution of HPV types was similar by HIV status. Screening strategies incorporating HPV genotyping and vaccination should be effective in preventing cervical cancer in both HIV-positive and -negative women living in sub-Saharan Africa.

Project description:BackgroundHuman papillomavirus genotypes 52 and 58 (HPV52/58) are frequently detected in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) in East Asian countries including Japan. As with other HPV genotypes, HPV52/58 consist of multiple lineages of genetic variants harboring less than 10% differences between complete genome sequences of the same HPV genotype. However, site variations of nucleotide and amino acid sequences across the viral whole-genome have not been fully examined for HPV52/58. The aim of this study was to investigate genetic variations of HPV52/58 prevalent among Japanese women by analyzing the viral whole-genome sequences.MethodsThe entire genomic region of HPV52/58 was amplified by long-range PCR with total cellular DNA extracted from cervical exfoliated cells isolated from Japanese patients with CIN or ICC. The amplified DNA was subjected to next generation sequencing to determine the complete viral genome sequences. Phylogenetic analyses were performed with the whole-genome sequences to assign variant lineages/sublineages to the HPV52/58 isolates. The variability in amino acid sequences of viral proteins was assessed by calculating the Shannon entropy scores at individual amino acid positions of HPV proteins.ResultsAmong 52 isolates of HPV52 (CIN1, n = 20; CIN2/3, n = 21; ICC, n = 11), 50 isolates belonged to lineage B (sublineage B2) and two isolates belonged to lineage A (sublineage A1). Among 48 isolates of HPV58 (CIN1, n = 21; CIN2/3, n = 19; ICC, n = 8), 47 isolates belonged to lineage A (sublineages A1/A2/A3) and one isolate belonged to lineage C. Single nucleotide polymorphisms specific for individual variant lineages were determined throughout the viral genome based on multiple sequence alignments of the Japanese HPV52/58 isolates and reference HPV52/58 genomes. Entropy analyses revealed that the E1 protein was relatively variable among the HPV52 isolates, whereas the E7, E4, and L2 proteins showed some variations among the HPV58 isolates.ConclusionsAmong the HPV52/58-positive specimens from Japanese women with CIN/ICC, the variant distributions were strongly biased toward lineage B for HPV52 and lineage A for HPV58 across histological categories. Different patterns of amino acid variations were observed in HPV52 and HPV58 across the viral whole-genome.

Project description:A substantial effect of human papillomavirus (HPV) vaccines on reducing HPV-related cervical disease is essential before modifying clinical practice guidelines in partially vaccinated populations.To determine the population-based cervical intraepithelial neoplasia (CIN) trends when adjusting for changes in cervical screening practices that overlapped with HPV vaccination implementation.The New Mexico HPV Pap Registry, which captures population-based estimates of both cervical screening prevalence and CIN, was used to compute CIN trends from January 1, 2007, to December 31, 2014. Under New Mexico Administrative Code, the New Mexico HPV Pap Registry, a statewide public health surveillance program, receives mandatory reporting of all cervical screening (cytologic and HPV testing) and any cervical, vulvar, and vaginal histopathological findings for all women residing in New Mexico irrespective of outcome.Prespecified outcome measures included low-grade CIN (grade 1 [CIN1]) and high-grade CIN (grade 2 [CIN2] and grade 3 [CIN3]).From 2007 to 2014, a total of 13?520 CIN1, 4296 CIN2, and 2823 CIN3 lesions were diagnosed among female individuals 15 to 29 years old. After adjustment for changes in cervical screening across the period, reductions in the CIN incidence per 100?000 women screened were significant for all grades of CIN among female individuals 15 to 19 years old, dropping from 3468.3 to 1590.6 for CIN1 (annual percentage change [APC], -9.0; 95% CI, -12.0 to -5.8; P?<?.001), from 896.4 to 414.9 for CIN2 (APC, -10.5; 95% CI, -18.8 to -1.2; P?=?.03), and from 240.2 to 0 for CIN3 (APC, -41.3; 95% CI, -65.7 to 0.3; P?=?.05). Reductions in the CIN2 incidence were also significant for women 20 to 24 years old, dropping from 1027.7 to 627.1 (APC, -6.3; 95% CI, -10.9 to -1.4; P?=?.02).Population-level decreases in CIN among cohorts partially vaccinated for HPV may be considered when clinical practice guidelines for cervical cancer screening are reassessed. Evidence is rapidly growing to suggest that further increases in raising the age to start screening are imminent, one step toward integrating screening and vaccination.

Dataset Information

Distribution of high-risk human papillomavirus genotypes among HIV-negative women with and without cervical intraepithelial neoplasia in South Africa.

Objective

Methods

Results

Conclusion

Publications

Distribution of high-risk human papillomavirus genotypes among HIV-negative women with and without cervical intraepithelial neoplasia in South Africa.

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