Genome, HLA and polygenic risk score analyses for prevalent and persistent cervical human papillomavirus (HPV) infections.

Genetic variants that underlie susceptibility to cervical high-risk human papillomavirus (hrHPV) infections are largely unknown. We conducted discovery genome-wide association studies (GWAS), replication, meta-analysis and colocalization, generated polygenic risk scores (PRS) and examined the association of classical HLA alleles and cervical hrHPV infections in a cohort of over 10,000 women. We identified genome-wide significant variants for prevalent hrHPV around LDB2 and for persistent hrHPV near TPTE2, SMAD2, and CDH12, which code for proteins that are significantly expressed in the human endocervix. Genetic variants associated with persistent hrHPV are in genes enriched for the antigen processing and presentation gene set. HLA-DRB1*13:02, HLA-DQB1*05:02 and HLA-DRB1*03:01 were associated with increased risk, and HLA-DRB1*15:03 was associated with decreased risk of persistent hrHPV. The analyses of peptide binding predictions showed that HLA-DRB1 alleles that were positively associated with persistent hrHPV showed weaker binding with peptides derived from hrHPV proteins and vice versa. The PRS for persistent hrHPV with the best model fit, had a P-value threshold (PT) of 0.001 and a p-value of 0.06 (-log10(0.06) = 1.22). The findings of this study expand our understanding of genetic risk factors for hrHPV infection and persistence and highlight the roles of MHC class II molecules in hrHPV infection.

Secular trend in interobserver agreement of VIA diagnosis for cervical cancer screening in Nigeria.

OBJECTIVE: In low resource settings, visual inspection with acetic acid (VIA) by allied health workers, has been suggested as an alternative for cervical cancer screening. However, there are concerns about the objectivity and time to diagnostic concordance with specialists. We evaluated the secular trend in interobserver agreement between nurse providers and a gynecologist/colposcopist over a five-year period. METHODS: Nurses provided VIA screening with digital cervivography to 4,961 participants in five screening clinics from October 2010 to May 2014 in Nigeria in this observational study. Cervigraphs were reviewed at meetings where a gynaecologist/colposcopist made an assessment from the cervigraphs. We used weighted kappa statistics to calculate agreement in diagnosis between nurse providers and the gynecologist/colposcopist; linear regression models to examine overall trend and investigate potential clinic characteristics that may influence agreement; and time series models to characterize month to month variations. RESULTS: Mean age of participants was 37±8 years. Overall agreement was 0.89 at Site D, 0.78 and 0.73 at Sites A and C respectively, 0.50 for Site E and 0.34 for Site C. The number of trainings attended by nurse providers(ß = 0.47,95%CI:0.02-0.93, p = 0.04), high level of engagement by site gynecologists(ß = 0.11,95%CI:0.01-0.21,p = 0.04) were associated with increased agreement; while increasing distance from the coordinating site(ß = -0.47,95%CI:-0.92-0.02,p = 0.04) was associated with decreased agreement. There were no associations between number of years screening clinics were operational(ß = 0.01,95%CI: -0.01-0.03,p = 0.29), cumulative experience of nurse providers(ß = 0.04,95%CI:-0.03-0.12,p = 0.19) and agreement. There were no significant increases in weighted kappa statistics over time for all sites considered. Monthly variations were significant for only one of two sites considered in time series models (AR1 term = -0.40, 95%CI:-0.71-0.09,p = 0.01). CONCLUSION: Our results showed a lack of objectivity, persistent variation and lack of convergence of diagnostic capabilities of nurse led VIA cervical cancer screening with the diagnostic capabilities of a specialist in a cervical cancer screening program in Nigeria.

Developing National Cancer Registration in Developing Countries - Case Study of the Nigerian National System of Cancer Registries.

The epidemiological transition in sub-Saharan Africa (SSA) has given rise to a concomitant increase in the incidence of non-communicable diseases including cancers. Worldwide, cancer registries have been shown to be critical for the determination of cancer burden, conduct of research, and in the planning and implementation of cancer control measures. Cancer registration though vital is often neglected in SSA owing to competing demands for resources for healthcare. We report the implementation of a system for representative nation-wide cancer registration in Nigeria - the Nigerian National System of Cancer Registries (NSCR). The NSCR coordinates the activities of cancer registries in Nigeria, strengthens existing registries, establishes new registries, complies and analyses data, and makes these freely available to researchers and policy makers. We highlight the key challenges encountered in implementing this strategy and how they were overcome. This report serves as a guide for other low- and middle-income countries (LMIC) wishing to expand cancer registration coverage in their countries and highlights the training, mentoring, scientific and logistic support, and advocacy that are crucial to sustaining cancer registration programs in LMIC.