Association of plasma aflatoxin with persistent detection of oncogenic human papillomaviruses in cervical samples from Kenyan women enrolled in a longitudinal study.

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.

Association of Plasma Aflatoxin With Persistent Detection of Oncogenic Human Papillomaviruses in Cervical Samples From Kenyan Women Enrolled in a Longitudinal Study.

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.

Human Immunodeficiency Virus Type 1 RNA Genital Tract Shedding After Cryotherapy for Cervical Intraepithelial Neoplasia in Western Kenya.

This prospective study of 39 women living with human immunodeficiency virus (HIV) on antiretroviral therapy in Western Kenya aimed to quantify genital tract HIV-1 RNA (GT-HIV RNA) shedding before and after cryotherapy for cervical intraepithelial neoplasia. Most GT-HIV RNA shedding was detected precryotherapy, suggesting that cryotherapy was not the primary cause of shedding.

A community-based approach to cervical cancer prevention in western Kenya: An AMPATH feasibility project.

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.

Persistence of oncogenic and non-oncogenic human papillomavirus is associated with human immunodeficiency virus infection in Kenyan women.

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.

Detection of types of HPV among HIV-infected and HIV-uninfected Kenyan women undergoing cryotherapy or loop electrosurgical excision procedure.

OBJECTIVE: To assess the baseline types of HPV infection among HIV-positive and HIV-negative 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.

Loop Electrosurgical Excision Procedure Treats Cervical Intraepithelial Neoplasia 2/3 Among HIV- and HIV+ Women in Kenya.

OBJECTIVE: The aim of the study was to compare loop electrosurgical excision procedure (LEEP) as treatment for cervical intraepithelial neoplasia (CIN) 2/3 in HIV- versus HIV+ women. MATERIALS AND METHODS: Seventy-five HIV- and 75 HIV+ women at 6 months or more after LEEP for CIN 2/3 were enrolled between September 2013 and November 2014 in this prospective cohort study at the cervical cancer screening clinic in Eldoret, Kenya. Visual inspection with acetic acid (VIA), followed by cervical cytology with conventional cytology, was performed on all women. Women with positive VIA or abnormal cervical cytology underwent colposcopy/biopsy. Lesion progression, persistence, and regression were assessed to quantify the efficacy of LEEP. RESULTS: Post-loop electrosurgical excision procedure screening test showed both a negative VIA and normal cervical cytology in 64 (85%) of HIV- and 57 (77%) HIV+ women (risk difference = 8.3%, CI = -4.2% to 21%, p = .20). Eleven (15%) HIV- and 17 (23%) HIV+ (p = .20) women had positive VIA, abnormal cervical cytology, or both and were referred for colposcopy/biopsy. Twenty-one (8 HIV-, 13 HIV+) women were biopsied. Of the 8 HIV- women, 4 (50%) had CIN lesions that regressed, 3 (38.0%) persisted, and 1 (12%) progressed to invasive cancer after LEEP. Of the 13 HIV+ women, 6 (46%) had CIN lesions that regressed, 7 (54%) had CIN lesions that persisted, and no HIV+ women had CIN lesions that progressed after LEEP. There was no difference in estimated efficacies of LEEP for HIV- and HIV+ women (92.7% versus 89.4%, risk difference = 3.3%, CI = -4.8% to 15.3%, p = .85). CONCLUSIONS: Loop electrosurgical excision procedure for CIN 2/3 is effective treatment for HIV- and HIV+ women in low-resource settings. Future efforts should improve follow-up after treatment.

Predictors of contraceptive implant uptake in the immediate postpartum period: a cross-sectional study.

Objectives: The aim of the study was to investigate how to improve access to family planning and address unmet contraceptive need in postpartum women, by determining the predictors of contraceptive implant uptake in the immediate postpartum period.Methods: A descriptive cross-sectional study was conducted among women who had given birth up to 6 d earlier at the Riley Mother and Baby Hospital, which is part of the Moi Teaching and Referral Hospital in Eldoret, Kenya. Participants were systematically sampled and data collected using pre-tested interviewer-administered questionnaires. Statistical analyses were performed to determine associations between variables. Logistic regression was used to determine the relationship between variables and contraceptive implant uptake.Results: The study comprised 353 women. Most (92%) were Christians and were married (74%). More than 76% had received secondary education or above; 9% were HIV-positive. Most (87%) had heard of the contraceptive implant and almost half (46%) had ever used it before their current pregnancy. Older women (p = .036), those who had reached their desired family size (p = .003), those who had planned for the current pregnancy (p = .027), those who had used the implant before (p < .001) and those who were HIV-positive (p = .001) were more likely to agree to use the contraceptive implant.Conclusions: Older age, achievement of family size, previous use of the same method, HIV positivity and planned pregnancy positively predicted uptake of the contraceptive implant.

Detection and Concentration of Plasma Aflatoxin is Associated with Detection of Oncogenic Human Papillomavirus in Kenyan Women.

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, as 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 co-factor. METHODS: Demographics, behavioral data, plasma, and cervical swabs were collected from 88 HIV-uninfected Kenyan women without cervical dysplasia. HPV detection was compared between women with or without plasma 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. AFB1-lys detection was not associated with age, being married, having more than secondary school education, home ownership, living at a walking distance to health care ≥60 minutes, number of lifetime sex partners, or age of first sex. AFB1-lys detection and plasma concentrations were associated with detection of oncogenic HPV types. CONCLUSIONS: 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 if aflatoxin interacts with HPV in a synergistic manner to increase the risk of cervical cancer.

Use of Palliative Cisplatinum for Advanced Cervical Cancer in a Resource-Poor Setting: A Case Series From Kenya.

PURPOSE: To evaluate the effectiveness and feasibility of cisplatinum for palliative treatment of advanced cervical cancer in a resource-poor setting. METHODS: An observational case series is reported from a university teaching hospital in Kenya. All women presenting with advanced cervical cancer and planned for palliative cisplatinum therapy from 2010 to 2014 were included. Women were treated with cisplatinum 50 mg/m2 every 4 weeks in an outpatient setting. Data on tumor stage and symptoms control were prospectively collected in an electronic database. The main outcome measure was control of symptoms such as bleeding, discharge, and pain. RESULTS: Of the women who originally presented with bleeding, 62% reported improvement in this symptom, 31.3% reported the bleeding completely stopped, 58% had improvement of their vaginal discharge, and 20.5% reported complete resolution. Of the women who presented with pain, 54% reported improvement; 30.9% reported pain had completely resolved. After each treatment cycle, approximately 30% of patients did not return for their next treatment. CONCLUSION: Cisplatinum as palliative treatment of advanced cervical cancer is feasible in a resource-poor setting and leads to effective symptom control. However, unknown barriers may inhibit women from returning for regular treatment.

Development of a comprehensive and sustainable gynecologic oncology training program in western Kenya, a low resource setting.

To provide information on the development of a gynecologic oncology training program in a low-resource setting in Kenya. This is a review of a collaboration between Kenyan and North American physicians who worked together to develop a gynecologic oncology training in Kenya. We review the published data on the increase of cancer incidence in sub-Saharan Africa and outline the steps that were taken to develop this program. The incidence of cervical cancer in Kenya is very high and is the leading cause of cancer mortality in Kenya. WHO identifies cancer as a new epidemic affecting countries in sub-Saharan Africa. In Kenya, a country of 45 million, there is limited resources to diagnose and treat cancer. In 2009 in western Kenya, at Moi University there was no strategy to manage oncology in the Reproductive Health department. There was only 1 gynecologic oncologists in Kenya in 2009. A collaboration between Canadian and Kenya physicians resulted in development of a gynecologic oncology clinical program and initiation of fellowship training in Kenya. In the past 4 years, five fellows have graduated from a 2 year fellowship training program. Integration of data collection on all the patients as part of this program provided opportunities to do clinical research and to acquire peer reviewed grants. This is the first recognized fellowship training program in sub-Saharan Africa outside of South Africa. It is an example of a collaborative effort to improve women's health in a low-resource country. This is a Kenyan managed program through Moi University. These subspecialty trained doctors will also provide advice that will shape health care policy and provide sustainable expertise for women diagnosed with a gynecologic cancer.