Cost-effectiveness analysis of alternative screening strategies for the detection of cervical cancer among women in rural areas of Western Kenya

While the incidence of cervical cancer has dropped in high-income countries due to organized cytology-based screening programs, it remains the leading cause of cancer death among women in Eastern Africa. Therefore, the World Health Organization(WHO) now urges providers to transition from widely prevalent but low-performance visual inspection with acetic acid (VIA) screening to primary human papillomavirus(HPV) DNA testing. Due to high HPV prevalence, effective triage tests are needed to identify those lesions likely to progress and so avoid over-treatment. To identify the optimal cost-effective strategy, we compared the VIA screen-and-treat approach to primary HPV DNA testing with p16/Ki67 dual-stain cytology or VIA as triage. We used a Markov model to calculate the budget impact of each strategy with incremental quality-adjusted life years and incremental cost-effectiveness ratios (ICER) as the main outcome. Deterministic cost-effectiveness analyses show that the screen-and-treat approach is highly cost-effective (ICER 2469 Int$), while screen, triage, and treat with dual staining is the most effective with favorable ICER than triage with VIA(ICER 9943 Int$ compared with 13,177 Int$). One-way sensitivity analyses show that the results are most sensitive to discounting, VIA performance, and test prices. In the probabilistic sensitivity analyses, the triage option using dual stain is the optimal choice above a willingness to pay threshold of 7115 Int$ being cost-effective as per WHO standards. The result of our analysis favors the use of dual staining over VIA as triage in HPV-positive women and portends future opportunities and necessary research to improve the coverage and acceptability of cervical cancer screening programs

Human immunodeficiency virus type 1 RNA genital tract shedding after cryotherapy for cervical intraepithelial neoplasia in Western Kenya

Abstract :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

HIV-1 RNA genital tract shedding after cryotherapy for visual inspection with acetic acid-positive cervical lesions in western Kenya

Objectives: To quantify genital tract HIV-1 RNA (GT-HIV RNA) shedding among women living with HIV (WLHIV) before and after cryotherapy treatment for visual inspection with acetic acid (VIA) positive cervical lesions. Methods:We conducted a prospective, longitudinal study of 39 WLHIV on antiretroviral treatment (ART) undergoing cryotherapy for VIA positive lesions in Kenya from 2015-2017. Eligibility for cryotherapy were lesions that covered Results: Detectable GT-HIV RNA was found in 4/39 (10%) participants pre-cryotherapy, 1/30 (3.3%) and 3/26 (11.5%) participants at the 2- and 8-weeks post-cryotherapy, respectively. Only 6/39 (13%) participants had detectable GT-HIV RNA at any point during the study. 2/6 had recent high PVL (range: 49,124-150,695 copies/mL) within 3 months of starting the study and detectable GT-HIV RNA at follow-up visits. 4/6 had undetectable recent PVL within 3-11 months of the study but each had detectable GT-HIV RNA pre-cryotherapy. The mean GT-HIV RNA among 4/39 WLHIV with shedding at pre-cryotherapy was 43,109 (range: 21,812-73,625) copies/mL. Only one participant had GT-HIV RNA (73,125 copies/mL) at 2-weeks post-cryotherapy (N=30); she had no shedding pre-cryotherapy but had a PVL of 49,124 copies/mL 3 months before the study. The mean GT-HIV RNA at 8-weeks post-cryotherapy (N=26) was 44,668 (range: 21,256-64,812) copies/mL among three participants. One of the 3 had high PVL of 150,695 copies/mL 3 months prior to cryotherapy while 2/3 had GT-HIV RNA shedding at baseline despite undetectable most recent PVL. However, their undetectable PVL was 8-11 months prior to cryotherapy which may not accurately reflect PVL at baseline. Conclusions: The majority of GT-HIV RNA shedding was detected before cryotherapy. This finding suggests that cryotherapy was not the primary cause of GT-HIV RNA shedding. Non-adherence to ART might have played a major role. The small sample size and failure to perform paired GT-HIV RNA and PVL tests at each visit are limitations of the study. Further research on the effect of cryotherapy on GT-HIV RNA shedding in ART non-adherent compared to ART-adherent WLHIV is needed

Longer duration of anti-retroviral therapy is associated with decreased risk of human papillomaviruses detection in Kenyan women living with HIV

Objective: A longitudinal study was conducted among women living with HIV in Kenya to determine if duration of anti-retroviral (ART) usage altered detection and persistence of oncogenic (high-risk) human papillomaviruses (HR-HPV). Methods: Women living with HIV without cervical dysplasia were enrolled at a cervical cancer screening clinic. Three cervical swabs, HIV viral loads, and CD4 cell counts were obtained at enrollment and at two annual visits. HPV genotyping was performed on swabs (Roche Linear Array). Linear regression models assessed effects of ART duration on HR-HPV detection and persistence. Results: Seventy-seven women, median age 38 years, completed three study visits and were included in the analysis. The mean time from HIV diagnosis to enrollment was 9.6 years (SD 3.9 years). The mean ART duration was 6.2 years (SD 3.1 years). Most women had undetectable HIV viral loads and CD4 cell counts above 500 cells/L. Each additional year of ART use reduced the likelihood of detection of HR-HPV by 10-15% and persistent detection of A9 HR-HPV by 20%. Conclusion: Among Kenyan women living with HIV, longer duration of ART use was associated with significantly reduced risk of all detection and persistent detection of HR-HPV

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

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

Cryotherapy and LEEP are effective treatment for CIN lesions in HIV+ and HIV- women in western Kenya

Objectives: Cervical cancer is the third most common cancer worldwide and the most common cancer among Kenyan women, with an age-standardized incidence rate of 33.8% in 2018. Cervical intraepithelial neoplasia (CIN) caused by human papillomavirus (HPV) in HIV+ women is over twice as likely to progress in severity compared to HIV- women. Conflicting reports exist as to the efficacy of cryotherapy or loop electrosurgical excision procedure (LEEP) as treatment for CIN among HIV+ women. This study assesses the results of cryotherapy or LEEP for CIN among HIV+ compared to HIV- women in Western Kenya. Methods: One-hundred and twenty HIV+ (60 cryotherapy, 60 LEEP) and 120 HIV- (60 cryotherapy and 60 LEEP) women were intended to be enrolled after a positive visual inspection with acetic acid (VIA). However, only 86 HIV+ (39 cryotherapy, 47 LEEP) and 89 HIV- (46 cryotherapy, 43 LEEP) who had follow-up of 24 months were included in this analysis. Women were eligible for cryotherapy if the lesion covered low grade intraepithelial lesion (LSIL) on Pap smear or ≥ CINI on histology, LEEP failure was defined as high grade intraepithelial lesion (HSIL) on Pap smear or ≥ CIN 2 after treatment. Chi square and Fishers’ exact tests were used to compare the proportions. Results: There was no statistically significant difference in treatment failure rates between HIV+ and HIV- patients (10.1% v 19.8% p =0.09). Among patients who underwent cryotherapy, there was no statistically significant difference in treatment failure between HIV+ and HIV- women (18% v 4.4%, p = 0.073). No statistically significant difference in treatment failure was observed among HIV+ and HIV- women who underwent LEEP (16.3% v 21.3%, p = 0.599). No statistically significant difference in treatment failure was observed between all patients in the LEEP arm compared to those in the cryotherapy arm (10.6% v 18.9% p =0.141). Seventy-four percent of HIV+ women were on antiretroviral therapy (ART) during the study, and 91% had been on ART during or prior to the study. Mean CD4 count among HIV+ women was 580. Conclusions: In our experience, cryotherapy and LEEP are effective treatment for HIV+ and HIV- women if done for appropriate CIN lesions in low-resource settings

AMPATH Oncology: Baseline HPV detection in Kenyan women enrolled in a longitudinal study of modifiable factors predicting cervical dysplasia.

Background: Cervical cancer is caused by oncogenic HPV types. Kenyan women, HIV-infected or uninfected were studied to define modifiable factors predicting incidence and persistence of HPV and cervical dysplasia. Methods: From 9/21/2015 to 10/4/2016, 223 women ages 18 to 45 years old with normal VIA at enrollment were enrolled in a longitudinal study in Kenya. Cervical swabs, behavioral data, and other data were collected. HPV typing was performed on clinician-obtained cervical swabs using the Roche Linear Array. Results: Analysis of 219 evaluable participants was done, including 115 HIV-infected (median age 36 years) and 104 HIV-uninfected women (median age 33 years) (p = .0009). Among HIV-infected women, 86.8% were receiving anti-retroviral therapy (ART); median duration between HIV diagnosis and enrollment was 7.2 years (IQR 4.1-10.3); median CD4 count was 471 (IQR 310-612). There was a significant difference in number of lifetime sex partners between HIV-infected (median 4, IQR 3-8) and HIV-uninfected women (median 3, IQR 1.5-4), p = .0001. HPV detection is shown in Table 1. Conclusions: Oncogenic HPV types, including types preventable by vaccination were prevalent in Kenyan women. HIV-infected women were more likely to have detection of HPV 16, other oncogenic HPV types, and multiple types in spite of ART. In this longitudinal study, other factors will be included such as behaviors, the effect of HIV viral load, CD4 count, and details of ART

Comparison of HPV detection in HIV-infected and HIV-uninfected Kenyan women with or without cervical dysplasia.

Background: Cervical cancer, a malignancy caused by human papillomavirus (HPV) infection, is the most common malignancy in women living in sub-Saharan African countries including Kenya. HIV co-infection accelerates the natural course of cervical cancer. To determine the specific HPV type distribution in HIV-infected women compared to HIV-uninfected women, with and without evidence of cervical dysplasia. Methods: Demographic information, behavioral data, and a cervical swab were collected from women 18 and 45 years of age, HIV-infected or HIV-uninfected, who presented for cervical cancer screening at Moi Referral and Teaching Hospital in Eldoret, Kenya. Women were triaged based on the presence or absence of cervical dysplasia. HPV testing was performed using the Roche Linear Array Assay. Results were compared between women with or without HIV co-infection and between those with or without cervical dysplasia, using Chi-square tests or Fisher’s exact tests. Results: 223 women had normal VIAs. All had HPV testing, 221 had valid results: 115 HIV-infected women (mean age 37 years) and 106 HIV-uninfected (mean age 33 years). 175 women had abnormal VIAs. 143 women had HPV testing performed, 140 had valid results: 70 HIV-infected women (mean age 38.5 years) and 70 HIV-uninfected (mean age 31.3 years). Greater than 90% of all HIV-infected women in both projects were receiving anti-retroviral therapy at enrollment. HPV of any type was detected in 48% of all women with normal VIA vs. 61% of women with abnormal VIA (P = 0.018). High risk (HR)-HPV was detected in 38% of all women with normal VIA vs. 51% of all women with abnormal VIA (P = 0.012). HIV-uninfected women with normal VIA had significantly lower detection of all HPV (P = 0.026), high risk-HPV (P = 0.018), IARC high risk-HPV (P = 0.047), A9 types (P = 0.050), and individual types HPV 16 (P = 0.0274), HPV 18 (P = 0.007), and HPV 51 (P = 0.009) than HIV-uninfected women with abnormal VIA. Among HIV-infected women, there was no difference in detection of any group of HPV types or individual types with respect to VIA results. Conclusions: HIV-uninfected women without cervical dysplasia had lower detection of oncogenic HPV than HIV-uninfected women with dysplasia. In contrast, HPV detection did not differ among HIV-infected women between those with or without cervical dysplasia. In addition, VIA appears to lack specificity for HPV-associated cervical dysplasia, as 39% of women with abnormal VIA examinations did not have any HPV detected, and 49% of women with abnormal VIA examinations did not have any HR-HPV detected

Loss to follow-up in a cervical cancer screening and treatment program in western Kenya

Background: Increasingly, evidence is emerging from developing countries like Kenya on the burden of loss to follow-up care after a positive cervical cancer screening/diagnosis, which impacts negatively on cervical cancer prevention and control. Unfortunately little or no information exists on the subject in the western region of Kenya. This study is designed to determine the proportion of and predictors and reasons for defaulting from follow-up care after positive cervical cancer screen. Aim: To determine the rates and factors associated with loss to follow-up in a multivisit cervical cancer screening and treatment program in western Kenya. Methods: We conducted a prospective study of women, who presented for cervical cancer screening at Chulaimbo and Webuye subcounty hospitals, and screened positive by VIA. A 2-3 weeks appointment was then set for review by a gynae-oncologist. A total of 100 women, scheduled for review, were recruited in the study and followed between August 2016 and May 2017. LTFU was defined as failure to keep a second rescheduled appointment or being unreachable for 3 consecutive months and failure to confirm that a woman sought for care in another health facility. Descriptive statistics was used for summary and the Cox regression model was used to estimate the risk of LTFU for different covariates. Results: The age range was 21-77 years, with a mean of 44.45 years. 39% of the women defaulted from scheduled follow-up appointment of which 25 (64%) were LTFU. Univariate Cox regression was conducted for HIV cases (HR=2.7, P value=0.021), clinic revisits (HR=2.6, P value=0.026), married (HR=0.63, P value=0.237) and previously screened women (HR=1.67, P value=0.198). Increased risk of LTFU was observed for HIV cases (HR=2.4, P value=0.04) and revisits (HR=7.5, P value=0.014) in an adjusted model. Conclusion: LTFU affects cervical cancer management due to several factors some of which are beyond the control of the women. We recommend a larger study be replicated for ease of generalizability of results; awareness and strategies are required to retain them to obey the treatment appointment since they are the highly vulnerable