Evaluation of the effectiveness of high-risk human papilloma self-sampling test for cervical cancer screening in Bolivia.

BACKGROUND: In Bolivia the incidence and mortality rates of uterine cervix cancer are the highest in America. The main factor contributing to this situation is the difficulty of establishing and maintaining quality prevention programs based on cytology. We aimed to evaluate the effectiveness of HR-HPV testing on self-collected samples to detect cervical intra-epithelial neoplasia and identify the best combination of screening tests. METHODS: A total of 469 women, divided in two groups, were included in this study. The first group included 362 women that underwent three consecutively primary screening tests: self-collected sampling for HR-HPV detection, conventional cervical cytology and visual inspection under acetic acid (VIA). The second group included 107 women referred with a positive HR-HPV test that underwent conventional cervical cytology and VIA. The presence of high grade intraepithelial lesion (CIN 2+) or invasive cancer was verified by colposcopy and biopsy. RESULT: In the screening group the sensitivity to detect high grade intraepithelial lesion (CIN 2+) or invasive cancer were 100, 76, 44% for the VIA, HR-HPV test and cytology, respectively. In the referred group, the sensitivity to detect high grade intraepithelial lesion (CIN 2+) or invasive cancer by VIA and cytology were 100 and 81%, respectively. CONCLUSIONS: VIA and HR-HPV self-sampling were the best combination to detect CIN2+ lesions. Cytology analysis gave the poorest performance.

Assessment of a new low-cost, PCR-based strategy for high-risk human papillomavirus DNA detection for cervical cancer prevention.

BACKGROUND: HPV test implementation as a primary screening tool has the potential to decrease cervical cancer incidence as shown by several studies around the world. However, in many low-resource settings, the HPV test introduction has been backed down mainly due to its price. In this study, we present a novel low-cost strategy involving simple devices and techniques for high-risk human papillomavirus (HR-HPV) detection. The analytical performance to detect HR-HPV infections of this novel strategy was assessed by comparing it with the Hybrid Capture 2 system (HC2), which is used as gold standard. METHODS: Paired-cervical samples were collected from 541 women assisting to gynecological services in an outpatient clinic. One sample was transported in the Hybrid Capture Standard Transport Medium for HR-HPV detection by the HC2. The second sample was transported on glass slide for detection by PCR-based techniques (GP-EIA, BSGP-EIA and pU 1 M-L/2R). RESULTS: The level of agreement between the PCR-based techniques and HC2 system was determined with the Cohen's kappa value. The kappa values between HC2 and GP-EIA, BSGP-EIA and pU 1 M-L/2R were 0.71 (CI 95% 0.63-0.78), 0.78 (CI 95% 0.71-0.84) and 0.63 (CI 95% 0.55-0.72), respectively. However, when the results from both BSGP-EIA and pU 1 M-L/2R were combined, the level of agreement with HC2 was increased to 0.82 (CI 95% 0.76-0.88), reflecting a very good agreement between the two HR-HPV detection strategies. Furthermore, the sensitivity of both techniques combined was also increased compared to the BSGP-EIA (88.7% vs 77.4%) and the pU (88.7 vs 60.9%) without penalizing the specificity obtained with the BSGP-EIA (95.1% vs 96.9%) and the pU (95.1% vs 96.5%). CONCLUSIONS: This novel strategy, combining two PCR-based techniques for HR-HPV detection, could be useful for cervical cancer screening in self-collected samples in low-income countries.

Evaluation of the self-sampling for cervical cancer screening in Bolivia.

BACKGROUND: Incidence and mortality rates of cervical cancer in Bolivia are the highest in Latin America. Vaginal cell self-sampling can improve screening coverage. Information on common reasons for low screening coverage and preferences for future screening are essential to reduce cervical cancer incidence. We aimed to evaluate the knowledge about human papillomavirus (HPV) and cervical cancer of Bolivian women from urban, peri-urban and rural areas of Cochabamba and to determine their degree of acceptability and confidence towards vaginal HPV self-sampling. In addition, we assessed the impact of self-sampling on cervical cancer screening coverage in a selected peri-urban area. METHODS: We gathered information from women living in urban, peri-urban and rural areas of Cochabamba province in Bolivia using two different structured questionnaires. In Survey1, we collected information from 222 women about their knowledge on HPV and cervical cancer. In Survey 2, the acceptance and confidence towards vaginal HPV self-sampling compared to the physician-sampling was assessed in 221 women. A non-probabilistic stratified sampling by areas was carried out for the two questionnaires. In the third phase of the study, we determined the impact of HPV self-sampling collection on screening coverage in a peri-urban area of Cochabamba. RESULTS: Bolivian women knew little or nothing about cervical cancer and HPV infection in all areas. They all found self-sampling collection easier to perform (86.9 to 93.2%) and more comfortable (79.4 to 83.3%) compared to physician sampling. Sampling accuracy to detect cervical cancer was probably higher in their point of view when it was taken by physician (35.1 to 63.5%). However in rural areas women preferred self-sampling. Accordingly, the campaign of vaginal HPV self-sampling in this peri-urban area increased screening coverage, reaching in three months the annual rate average. CONCLUSIONS: The knowledge about cervical cancer and HPV infection is poor in Bolivia. Despite greater acceptance of the vaginal HPV self-sampling in all areas, women kept greater confidence in the screening performed by the gynecologist although HPV self-sampling improved coverage rate.

Self-sampling for human papillomavirus DNA detection: a preliminary study of compliance and feasibility in BOLIVIA.

BACKGROUND: Cervical cancer incidence and mortality rates in Bolivia are among the highest in Latin America. This investigation aims to evaluate the possibility of using simple devices, e.g. a cotton swab and a glass slide, for self-sampling in order to detect human papillomavirus (HPV) DNA by PCR in cervico-vaginal cells. METHODS: In the first phase of our study we evaluated the use of a glass slide as a transport medium for cervical cells. A physician took paired-cervical samples from 235 women. One sample was transported in Easyfix® solution and the other sample was smeared over a glass slide. Both were further analyzed and compared for human DNA recovery and HPV detection. A kappa value was determined to evaluate the agreement between the HPV DNA detection rates. In the second phase of the study, 222 women from the urban, peri-urban and rural regions of Cochabamba were requested to perform self-sampling using the following devices: a cotton swab combined with a glass slide, and a vaginal tampon. Women gave their opinion about the self-sampling technique. Finally, the agreement for high risk-HPV detection between self- and physician-collected samples was performed in 201 samples in order to evaluate the self-sampling technique. RESULTS: Firstly, the comparison between Easyfix® solution and the glass slide to transport clinical samples gave a good agreement for HPV DNA detection (κ = 0.71, 95% CI 0.60-0.81). Secondly, self-sampling, especially with cotton swab combined with glass slide, would generally be preferred over clinician sampling for a screening program based on HPV detection. Finally, we showed a good agreement between self- and physician collected samples for high risk-HPV detection (κ = 0.71, 95% CI 0.55-0.88). CONCLUSIONS: Simple devices such as a cotton swab and a glass slide can be used to perform self-sampling and HPV DNA detection. Furthermore, most Bolivian women preferred self-sampling over clinician-sampling for cervical cancer screening.

The pseudoenzyme PDX1.2 boosts vitamin B6 biosynthesis under heat and oxidative stress in Arabidopsis.

Vitamin B6 is an indispensable compound for survival, well known as a cofactor for numerous central metabolic enzymes and more recently for playing a role in several stress responses, particularly in association with oxidative stress. Regulatory aspects for the use of the vitamin in these roles are not known. Here we show that certain plants carry a pseudoenzyme (PDX1.2), which is involved in regulating vitamin B6 biosynthesis de novo under stress conditions. Specifically, we demonstrate that Arabidopsis PDX1.2 enhances the activity of its catalytic paralogs by forming a heterododecameric complex. PDX1.2 is strongly induced by heat as well as singlet oxygen stress, concomitant with an enhancement of vitamin B6 production. Analysis of pdx1.2 knockdown lines demonstrates that boosting vitamin B6 content is dependent on PDX1.2, revealing that this pseudoenzyme acts as a positive regulator of vitamin B6 biosynthesis during such stress conditions in plants.