Background: Cervical cancer is caused by oncogenic human papillomaviruses (HPV) and is one of the most common malignancies in women living in sub-Saharan Africa. Women infected with the human immunodeficiency virus (HIV) have a higher incidence of cervical cancer, but the full impact on HPV detection is not well understood, and associations of biological and behavioral factors with oncogenic HPV detection have not been fully examined. Therefore, a study was initiated to investigate factors that are associated with oncogenic HPV detection in Kenyan women. Methods: Women without cervical dysplasia were enrolled in a longitudinal study. Data from enrollment are presented as a cross-sectional analysis. Demographic and behavioral data was collected, and HPV typing was performed on cervical swabs. HIV-uninfected women (n = 105) and HIV-infected women (n = 115) were compared for demographic and behavioral characteristics using t-tests, Chi-square tests, Wilcoxon sum rank tests or Fisher's exact tests, and for HPV detection using logistic regression or negative binomial models adjusted for demographic and behavioral characteristics using SAS 9.4 software. Results: Compared to HIV-uninfected women, HIV-infected women were older, had more lifetime sexual partners, were less likely to be married, were more likely to regularly use condoms, and were more likely to have detection of HPV 16, other oncogenic HPV types, and multiple oncogenic types. In addition to HIV, more lifetime sexual partners was associated with a higher number of oncogenic HPV types (aIRR 1.007, 95% CI 1.007-1.012). Greater travel distance to the clinic was associated with increased HPV detection (aOR for detection of ≥ 2 HPV types: 3.212, 95% CI 1. 206-8.552). Older age (aOR for HPV 16 detection: 0.871, 95% CI 0.764-0.993) and more lifetime pregnancies (aOR for detection of oncogenic HPV types: 0.706, 95% CI, 0.565-0.883) were associated with reduced detection. Conclusion: HIV infection, more lifetime sexual partners, and greater distance to health-care were associated with a higher risk of oncogenic HPV detection, in spite of ART use in those who were HIV-infected. Counseling of women about sexual practices, improved access to health-care facilities, and vaccination against HPV are all potentially important in reducing oncogenic HPV infections.
Background Cervical cancer is common in Kenyan women. Cofactors in addition to infection with oncogenic human papillomavirus (HPV) are likely to be important in causing cervical cancer, because only a small percentage of HPV-infected women will develop this malignancy. Kenyan women are exposed to dietary aflatoxin, a potent carcinogen and immunosuppressive agent, which may be such a cofactor. Methods Demographics, behavioral data, plasma, and cervical swabs were collected from 88 human immunodeficiency virus-uninfected Kenyan women without cervical dysplasia. Human papillomavirus detection was compared between women with or without plasma aflatoxin B1-lysine (AFB1-lys) and evaluated in relation to AFB1-lys concentration. Results Valid HPV testing results were available for 86 women (mean age 34.0 years); 49 women (57.0%) had AFB1-lys detected and 37 (43.0%) had none. The AFB1-lys detection was not associated with age, being married, having more than secondary school education, home ownership, living at a walking distance to healthcare ≥60 minutes, number of lifetime sex partners, or age of first sex. The AFB1-lys detection and plasma concentrations were associated with detection of oncogenic HPV types. Conclusions The AFB1-lys positivity and higher plasma AFB1-lys concentrations were associated with higher risk of oncogenic HPV detection in cervical samples from Kenya women. Further studies are needed to determine whether aflatoxin interacts with HPV in a synergistic manner to increase the risk of cervical cancer.
Objectives: Cervical cancer is caused by persistent infection with oncogenic, or “high-risk” types of human papillomaviruses, and is the most common malignancy in Kenyan women. A longitudinal study was initiated to investigate factors associated with persistent human papillomavirus detection among HIV-infected and HIV-uninfected Kenyan women without evidence of cervical dysplasia. Methods: Demographic/behavioral data and cervical swabs were collected from HIV-uninfected women (n = 82) and HIV-infected women (n = 101) at enrollment and annually for 2 years. Human papillomavirus typing was performed on swabs (Roche Linear Array). Logistic regression models of human papillomavirus persistence were adjusted for demographic and behavioral characteristics. Results: HIV-infected women were older and less likely to be married and to own a home and had more lifetime sexual partners than HIV-uninfected women. All HIV-infected women were receiving anti-retroviral therapy at enrollment and had satisfactory CD4 cell counts and HIV viral loads. One- and two-year persistent human papillomavirus detection was significantly associated with HIV infection for any human papillomavirus, high-risk human papillomavirus, International Agency for the Research on Cancer-classified high-risk human papillomavirus, and non-oncogenic “low-risk” human papillomavirus. Conclusion: Persistent detection of oncogenic and non-oncogenic human papillomavirus was strongly associated with HIV infection in Kenyan women with re-constituted immune systems based on satisfactory CD4 cell counts. In addition to HIV infection, factors associated with an increased risk of human papillomavirus persistence included a higher number of lifetime sex partners. Factors associated with decreased risk of human papillomavirus persistence included older age and being married. Further studies are needed to identify the immunological defects in HIV-infected women that allow human papillomavirus persistence, even in women receiving effective anti-retroviral therapy. Further studies are also needed to determine the significance of low-risk human papillomavirus persistence in HIV-infected women.
Objective: To assess the baseline types of HPV infection among HIV-positive and HIVnegative women in western Kenya undergoing cryotherapy or loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia. Methods: A prospective observational study was conducted of baseline HPV characteristics of women undergoing visual inspection with acetic acid (VIA) and cryotherapy or LEEP. After a positive VIA in HIV-positive and HIV-negative women, data on demographics, CD4 count, and use of antiretroviral therapy and a cervical swab were collected. HPV typing was performed using the Roche Linear Array. Results: Of 175 participants, 86 (49.1%) were HIV-positive and had a higher prevalence of low-risk HPV types (odds ratio [OR] 5.28, P=0.005) compared with HIV-negative women. The most common high-risk (HR)-HPV types in HIV-positive women were HPV 16 (13.9%) and HPV 18 (11.1%). HIV-positive women requiring LEEP were more likely to have HR-HPV types (OR 6.67, P=0.012) and to be infected with multiple HR-HPV types (OR 7.79, P=0.024) compared to those undergoing cryotherapy. Conclusion: HIV-positive women requiring LEEP versus cryotherapy had a higher prevalence of any HR-HPV type and multiple HR-HPV types. There were no such differences in HPV types identified among HIV-negative women.
The East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer, and to encourage collaborations between researchers in North America and East African countries. To date, studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on the persistence of HPV, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP. It will now be determined how HPV testing fits into cervical cancer screening programs in Kenya and Uganda, how aflatoxin influences immunological control of HIV, how HPV alters certain genes involved in the growth of tumours in HIV-infected women. Although there have been challenges in performing this research, with time, this work should help to reduce the burden of cervical cancer and other cancers related to HIV infection in people living in sub-Saharan Africa, as well as optimized processes to better facilitate research as well as patient autonomy and safety. KEY MESSAGES The East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer. Collaborations have been established between researchers in North America and East African countries for these studies. Studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on HPV detection, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP.
Background Cervical cancer is common among Kenyan women and is caused by oncogenic human papillomaviruses (HR-HPV). Identification of factors that increase HR-HPV persistence is critically important. Kenyan women exposed to aflatoxin have an increased risk of cervical HR-HPV detection. This analysis was performed to examine associations between aflatoxin and HR-HPV persistence. Methods Kenyan women were enrolled in a prospective study. The analytical cohort for this analysis included 67 HIV-uninfected women (mean age 34 years) who completed at least two of three annual study visits and had an available blood sample. Plasma aflatoxin was detected using ultra-high pressure liquid chromatography (UHPLC)-isotope dilution mass spectrometry. Annual cervical swabs were tested for HPV (Roche Linear Array). Ordinal logistic regression models were fitted to examine associations of aflatoxin and HPV persistence. Results Aflatoxin was detected in 59.7% of women and was associated with higher risk of persistent detection of any HPV type (OR = 3.03, 95%CI = 1.08–8.55, P = 0.036), HR-HPV types (OR = 3.63, 95%CI = 1.30-10.13, P = 0.014), and HR-HPV types not included in the 9-valent HPV vaccine (OR = 4.46, 95%CI = 1.13–17.58, P = 0.032). Conclusions Aflatoxin detection was associated with increased risk of HR-HPV persistence in Kenyan women. Further studies are needed to determine if aflatoxin synergistically interacts with HR-HPV to increase cervical cancer risk.
Objectives: Centralized programs have been ineffective in reducing the burden of cervical cancer among Kenyan women. A community-based pilot study was initiated to screen Kenyan women for cervical cancer and to vaccinate their children against human papillomavirus (HPV). Methods: Women were educated about cervical cancer prevention at community meetings. Women then provided self-collected vaginal swabs for oncogenic HPV testing using the Roche Cobas Assay. All women were then referred to the local clinic for Visual Inspection with Acetic Acid (VIA). Women were offered the quadrivalent HPV vaccine for their children if and when it became available for the study. Results: Women in western Kenya were invited to participate in community meetings. A total of 200 women were enrolled: 151 (75.5%) were HIV-uninfected and 49 (24.5%) were HIV-infected; the median age for all women was 42 years. High-risk (HR)-HPV types were detected in 49 of swabs from all 200 participants (24.5%) including 20.5% of HIV-uninfected women and 36.7% of HIV-infected women (P = .022). VIA was performed on 198 women: 192 had normal examinations and six had abnormal examinations. Five cervical biopsies revealed two cases of CIN 2 and one CIN 3. Although all mothers were willing to have their children (N = 432) vaccinated, the HPV vaccine could not be delivered to Kenya during the study period. Conclusions: Kenyan women were willing to attend community meetings to learn about prevention of cervical cancer, to provide self-collected vaginal swabs for HPV testing, to travel to the Webuye Clinic for VIA following the collection of swabs, and to have their children vaccinated against HPV. HR-HPV was prevalent, especially in HIV-infected women. As a result of this pilot study, this community-based strategy to prevent cervical cancer will be continued in western Kenya.
Background Cervical cancer is caused by oncogenic human papillomaviruses (HR-HPV) and is common among Kenyan women. Identification of factors that increase HR-HPV persistence is critically important. Kenyan women exposed to aflatoxin have an increased risk of HR-HPV detection in cervical specimens. This analysis was performed to examine associations between aflatoxin and HR-HPV persistence. Methods Kenyan women were enrolled in a prospective study. The analytical cohort for this analysis included 67 HIV-uninfected women (mean age 34 years) who completed at least two of three annual study visits and had an available blood sample. Plasma aflatoxin was detected using ultra-high pressure liquid chromatography (UHPLC)-isotope dilution mass spectrometry. Annual cervical swabs were tested for HPV (Roche Linear Array). Ordinal logistic regression models were fitted to examine associations of aflatoxin and HPV persistence. Results Aflatoxin was detected in 59.7% of women and was associated with higher risk of persistent detection of any HPV type (OR = 3.03, 95%CI = 1.08–8.55, P = 0.036), HR-HPV types (OR = 3.63, 95%CI = 1.30-10.13, P = 0.014), and HR-HPV types not included in the 9-valent HPV vaccine (OR = 4.46, 95%CI = 1.13–17.58, P = 0.032). Conclusions Aflatoxin detection was associated with increased risk of HR-HPV persistence in Kenyan women. Further studies, including mechanistic studies are needed to determine if aflatoxin synergistically interacts with HR-HPV to increase cervical cancer risk.
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