Reproducibility of a Rapid Human Papillomavirus Test at Different Levels of the Healthcare System in Tanzania: The AISHA Study.

BACKGROUND: To inform policy makers in Tanzania if and how best to implement rapid HPV testing, we assessed the interobserver reproducibility of careHPV test at three different levels of the healthcare system in an urban and a rural region of Tanzania. METHODS: Women aged 30 to 50 years were screened by careHPV testing in two primary healthcare centers (PHC), two district hospitals (DiH), and two regional hospitals (ReH). Aliquots were retested at regional (ReH) and national referral laboratories (NRL). Reproducibility was evaluated using agreement and kappa index measures. Intralaboratory reproducibility was also evaluated in a set of 10 positive and 10 negative samples. RESULTS: Samples from 1,134 women were locally tested and retested at ReH and/or NRL. Test results from Dar es Salaam ReH and Kilimanjaro PHC showed clear quality problems including suspicion of contamination during testing or aliquoting. After excluding these samples, 18.8% of 743 women were HPV positive at clinic level. The resulting careHPV reproducibility at different levels of the healthcare system was very good [agreement 95.7%, 95% confidence interval (CI), 94.0-96.9; kappa, 0.86, 95% CI, 0.81-0.91]. Intralaboratory agreement was also very good across four different experiments, with Fleiss' kappa between 0.87 (95% CI, 0.61-1.00) and 1.00 (0.75-1.00). CONCLUSIONS: Rapid HPV testing was highly reproducible between lower and higher levels of the healthcare system in Tanzania; however, performance seems to be operator dependent. IMPACT: The careHPV test seems to be a feasible option for cervical cancer screening in an organized, decentralized system and in limited-resource settings if quality assurance measures are in place.

Performance of an HPV 16/18 E6 oncoprotein test for detection of cervical precancer and cancer.

HPV testing is a better alternative for cervical cancer screening, but additional procedures are required for triage of HPV positive women. HPV encoded oncoproteins E6 and E7, as the main effectors of HPV carcinogenicity represent promising triage alternatives. To evaluate performance of the test, we included 155 women from a screening study and 59 from the same referral population attending colposcopy and with precancerous lesions. All were HPV-tested with HC2 and genotyped with LiPA, and cervical swabs were tested for HPV16/18 E6 oncoproteins. Histologic specimens were reviewed and adjudicated using p16 immunohistochemistry and 55 women had confirmed histologic HSIL, 31 (56.3%) associated with HPV 16/18, 23 with other HPV types and one HPV negative. Sensitivity and specificity were estimated with histologic HSIL/cancer as gold standard. E6 oncoprotein was detectable in all but one HSIL and in all cancers where HPV16/18 DNA was detected, but in none of the cases associated with other HPV types or HPV negatives. Among the few HPV16/18 DNA positive subjects initially without HSIL (n = 4) who were E6 oncoprotein positive, precancer was detected during follow-up in 2 out of 3 with available information. Estimated sensitivity for HPV16/18-related HSIL+ was 96.8% (95%CI = 83.8-99.8) and for all HSIL+ regardless of HPV type it was 56.4% (95%CI = 43.3-68.6). Specificity was 97.5% (95%CI = 93.7-99.0). E6 oncoprotein proved as a highly sensitive and specific marker for detection of HPV16/18-related HSIL lesions in this Honduran population with limited previous screening and may be useful as a triage method in screening programs, particularly in low income countries.

Endogenous hormones, inflammation, and body size in premenopausal Mexican women: results from the Mexican Teachers' Cohort (MTC, ESMaestras).

PURPOSE: Obesity is a major risk factor for several cancers, including female cancers. Endogenous hormones and inflammatory factors may mediate the association between anthropometric measures and cancer risk, although these associations have been studied mainly in Caucasians. The aim of the current study was to explore the association of circulating hormones, adipokines, and inflammatory factors with obesity and overweight in premenopausal Mexican women. METHODS: We conducted a cross-sectional analysis of 504 premenopausal women from the large Mexican Teachers' Cohort (MTC, ESMaestras) study to determine the association of insulin-like growth factor I (IGF-I), its major circulating binding protein (IGFBP-3), leptin, adiponectin, C-peptide, and C-reactive protein with comprehensive measures of body size. Biomarkers were measured by immunoassays. Multivariate regression analyses were performed to compare geometric mean biomarker concentrations with measured markers of body size and adiposity. RESULTS: Mean IGF-I and IGFBP-3 concentrations significantly increased with increasing height and leg length. Concentrations of IGF-I, adiponectin, and the IGF-I/IGFBP-3 ratio strongly decreased with increasing BMI, weight, waist and hip circumferences, waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR), while CRP, leptin, C-peptide concentrations, and the leptin/adiponectin ratio strongly increased. Adiponectin and the leptin/adiponectin ratio remained significantly related to measures of central adiposity (waist circumference, WHpR, and WHtR) after adjustment by body mass index. CONCLUSIONS: The results of our study suggest a strong relation between biomarkers and body size in this study population and suggest that different fat depots may have different metabolic properties.