Outcomes of cervical cancer among HIV-infected and HIV-uninfected women treated at the Brazilian National Institute of Cancer.
ABSTRACT: OBJECTIVE:We assessed mortality, treatment response, and relapse among HIV-infected and HIV-uninfected women with cervical cancer in Rio de Janeiro, Brazil. DESIGN:Cohort study of 87 HIV-infected and 336 HIV-uninfected women with cervical cancer. METHODS:Patients at the Brazilian National Institute of Cancer (2001-2013) were matched on age, calendar year of diagnosis, clinical stage, and tumor histology. Staging and treatment with surgery, radiotherapy, and/or chemotherapy followed international guidelines. We used a Markov model to assess responses to initial therapy, and Cox models for mortality and relapse after complete response (CR). RESULTS:Among 234 deaths, most were from cancer (82% in HIV-infected vs. 93% in HIV-uninfected women); only 9% of HIV-infected women died from AIDS. HIV was not associated with mortality during initial follow-up but was associated more than 1-2 years after diagnosis [overall mortality: stage-adjusted hazard ratio 2.02, 95% confidence interval (CI) 1.27-3.22; cancer-specific mortality: 4.35, 1.86-10.2]. Among 222 patients treated with radiotherapy, HIV-infected had similar response rates to initial cancer therapy as HIV-uninfected women (hazard ratio 0.98, 95% CI 0.58-1.66). However, among women who were treated and had a CR, HIV was associated with elevated risk of subsequent relapse (hazard ratio 3.60, 95% CI 1.86-6.98, adjusted for clinical stage). CONCLUSION:Among women with cervical cancer, HIV infection was not associated with initial treatment response or early mortality, but relapse after attaining a CR and late mortality were increased in those with HIV. These results point to a role for an intact immune system in control of residual tumor burden among treated cervical cancer patients.
Project description:US cervical cancer screening guidelines for human immunodeficiency virus (HIV)-uninfected women 30 years or older have recently been revised, increasing the suggested interval between Papanicolaou (Pap) tests from 3 years to 5 years among those with normal cervical cytology (Pap test) results who test negative for oncogenic human papillomavirus (HPV). Whether a 3-year or 5-year screening interval could be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown.To determine the risk of cervical precancer or cancer defined cytologically (high-grade squamous intraepithelial lesions or greater [HSIL+]) or histologically (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), as 2 separate end points, in HIV-infected women and HIV-uninfected women who at baseline had a normal Pap test result and were negative for oncogenic HPV.Participants included 420 HIV-infected women and 279 HIV-uninfected women with normal cervical cytology at their enrollment in a multi-institutional US cohort of the Women's Interagency HIV Study, between October 1, 2001, and September 30, 2002, with follow-up through April 30, 2011. Semiannual visits at 6 clinical sites included Pap testing and, if indicated, cervical biopsy. Cervicovaginal lavage specimens from enrollment were tested for HPV DNA using polymerase chain reaction. The primary analysis was truncated at 5 years of follow-up.Five-year cumulative incidence of cervical precancer and cancer.No oncogenic HPV was detected in 369 (88% [95% CI, 84%-91%]) HIV-infected women and 255 (91% [95% CI, 88%-94%]) HIV-uninfected women with normal cervical cytology at enrollment. Among these oncogenic HPV-negative women, 2 cases of HSIL+ were observed; an HIV-uninfected woman and an HIV-infected woman with a CD4 cell count of 500 cells/?L or greater. Histologic data were obtained from 4 of the 6 clinical sites. There were 6 cases of CIN-2+ in 145 HIV-uninfected women (cumulative incidence, 5% [95% CI, 1%-8%]) and 9 cases in 219 HIV-infected women (cumulative incidence, 5% [95% CI, 2%-8%]). This included 1 case of CIN-2+ in 44 oncogenic HPV-negative HIV-infected women with CD4 cell count less than 350 cells/?L (cumulative incidence, 2% [95% CI, 0%-7%]), 1 case in 47 women with CD4 cell count of 350 to 499 cells/?L (cumulative incidence, 2% [95% CI, 0%-7%]), and 7 cases in 128 women with CD4 cell count of 500 cells/?L or greater (cumulative incidence, 6% [95% CI, 2%-10%]). One HIV-infected and 1 HIV-uninfected woman had CIN-3, but none had cancer.The 5-year cumulative incidence of HSIL+ and CIN-2+ was similar in HIV-infected women and HIV-uninfected women who were cytologically normal and oncogenic HPV-negative at enrollment.
Project description:PURPOSE:To prospectively compare survival between human immunodeficiency virus (HIV)-infected versus HIV-uninfected cervical cancer patients who initiated curative chemoradiation therapy (CRT) in a limited-resource setting. METHODS AND MATERIALS:Women with locally advanced cervical cancer with or without HIV infection initiating radical CRT in Botswana were enrolled in a prospective, observational, cohort study from July 2013 through January 2015. RESULTS:Of 182 women treated for cervical cancer during the study period, 143 women initiating curative CRT were included in the study. Eighty-five percent of the participants (122 of 143) had stage II/III cervical cancer, and 67% (96 of 143) were HIV-infected. All HIV-infected patients were receiving antiretroviral therapy (ART) at the time of curative cervical cancer treatment initiation. We found no difference in toxicities between HIV-infected and HIV-uninfected women. The 2-year overall survival (OS) rates were 65% for HIV-infected women (95% confidence interval [CI] 54%-74%) and 66% for HIV-uninfected women (95% CI 49%-79%) (P = .70). Factors associated with better 2-year OS on multivariate analyses included baseline hemoglobin >10 g/dL (hazard ratio [HR] 0.37, 95% CI 0.19-0.72, P = .003), total radiation dose ?75 Gy (HR 0.52, 95% CI 0.27-0.97, P = .04), and age <40 years versus 40-59 years (HR 2.17, 95% CI 1.05-4.47, P = .03). CONCLUSIONS:Human immunodeficiency virus status had no effect on 2-year OS or on acute toxicities in women with well-managed HIV infection who initiated curative CRT in Botswana. In our cohort, we found that baseline hemoglobin levels, total radiation dose, and age were associated with survival, regardless of HIV status.
Project description:Since the initial recognition of acquired immunodeficiency syndrome (AIDS) in 1981, an increased burden of cervical cancer was identified among human immunodeficiency virus (HIV)-positive women. Introduction of antiretroviral therapy (ART) decreased risks of opportunistic infections and improved overall survival. HIV-infected women are living longer. Introduction of the human papillomavirus (HPV) vaccine, cervical cancer screening and early diagnosis provide opportunities to reduce cervical cancer associated mortality. In line with 2030 Sustainable Development Goals to reduce mortality from non-communicable diseases, increased efforts need to focus on high burden countries within sub-Saharan Africa (SSA). Despite limitations of resources in SSA, opportunities exist to improve cancer control. This article reviews advancements in cervical cancer control in HIV-positive women.
Project description: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.
Project description:OBJECTIVE:HIV-infected women on antiretroviral therapy have a higher risk of preterm birth than HIV-uninfected women in Botswana. To better understand the mechanism for preterm birth among HIV-infected women, we evaluated whether mid-trimester cervical length differed by HIV status as cervical shortening is associated with an increased risk for preterm birth. METHODS:We conducted a prospective cohort study among pregnant women receiving care at the Scottish Livingstone Hospital in Molepolole, Botswana. Consecutive women referred for routine obstetrical ultrasound were consented and enrolled if between 22w0d and 24w6d by ultrasound biometry. Blinded to maternal HIV status, an obstetrician measured transvaginal cervical length using standardized criteria. Cervical length, as well as the proportion of women with a short cervix (<25mm), were compared among HIV-infected and HIV-uninfected women. The acceptability of transvaginal ultrasound was also evaluated. RESULTS:Between April 2016 and April 2017, 853 women presenting for obstetric ultrasound were screened, 187 (22%) met eligibility criteria, and 179 (96%) were enrolled. Of those enrolled, 50 (28%) were HIV-infected (86% on antiretroviral therapy), 127 (71%) were HIV-uninfected, and 2 (1%) had unknown HIV status. There was no significant difference in mean cervical length between HIV-infected and HIV-uninfected women (32mm vs 31mm, p = 0.21), or in the proportion with a short cervix (10% vs 14%, p = 0.44). Acceptability data was available for 115 women who underwent a transvaginal ultrasound exam. Of these, 112 of 115 (97%) women deemed the transvaginal scan acceptable. CONCLUSIONS:The increased risk of preterm birth observed among HIV-infected women receiving antiretroviral therapy in Botswana is unlikely associated with mid-trimester cervical shortening. Further research is needed to understand the underlying mechanism for preterm birth among HIV-infected women.
Project description:BACKGROUND:Screening and treating premalignant cervical lesions (cervical intraepithelial neoplasia 2+ [CIN2+]) is an effective way to prevent cervical cancer, and recommendations exist for the monitoring of treatment success. Yet, there is no specific recommendation for human immunodeficiency virus (HIV)-infected women, who are at a known, increased risk of cervical cancer. METHODS:A systematic review was performed by searching MEDLINE, EMBASE, and Web of Science for studies published from January 1980 through May 2018. Eligible studies described the prevalence of histologically- and/or cytologically-defined lesions in HIV-infected women at least 6 months post-treatment. The primary endpoint was treatment failure, defined as the presence of residual and/or recurrent high-grade CIN2+/high-grade squamous intraepithelial lesions post-treatment. The pooled prevalence in HIV-infected women and the odds ratios (ORs) for HIV-infected compared to HIV-uninfected women were estimated using random-effects models. RESULTS:Among 40 eligible studies, the pooled prevalence of treatment failure in HIV-infected women was 21.4% (95% confidence interval [CI] 15.8-27.0). There was no significant difference in the treatment failure prevalence for cryotherapy (13.9%, 95% CI 6.1-21.6) versus loop electrosurgical excision procedure (13.8%, 95% CI 8.9-18.7; P = .9), but the treatment failure prevalence was significantly higher in women with positive (47.2%, 95% CI 22.0-74.0) than with negative (19.4%, 95% CI 11.8-30.2) excision margin (OR 3.4, 95% CI 1.5-7.7). Treatment failure was significantly increased in HIV-infected versus HIV-uninfected women, both overall (OR 2.7, 95% CI 2.0-3.5) and in all sub-group analyses. CONCLUSIONS:There is strong evidence for an increased risk of treatment failure in HIV-infected women, in comparison to their HIV-negative counterparts. The only significant predictor of treatment failure in HIV-infected women was a positive margin status, but further data is needed on long-term outcomes after ablative treatment in HIV-infected women.
Project description:BACKGROUND:Human papillomaviruses are the most important causative agents for invasive cervical cancer development. HPV type-specific vaccination and HPV cervical cancer screening methods are being widely recommended to control the disease but the epidemiology of the circulating HPV types may vary locally. The circulating HPV-strains have never been assessed in Burundi. This study determined the prevalence and genotype-specific distribution of HPV in four different strata in Burundi: HIV-infected or non-infected and women living in rural or urban areas. Implications for HPV diagnosis and vaccine implementation was discussed. METHODS:Four cross-sectional surveys were conducted in Burundi (2013 in a rural area and 2016 in urban area) among HIV-infected and uninfected women living in rural and urban areas. Liquid-Based Cytology (LBC) and HPV genotyping were performed and risk factors for HPV infection and cervical pre-cancer lesions were determined using logistic regression model. RESULTS:HPV prevalence was very high in urban area with significant differences between HIV-positive and negative women (p<0.0001). In fact, 45.7% of HIV-positive participants were infected with any HPV type and all were infected with at least one HR/pHR-HPV type. Among the HIV-negative participants, 13.4% were HPV-infected, of whom, only four women (2.7%) were infected with HR/pHR-HPV types. In rural area, HPV infection did not significantly differ between HIV-positive and negative women (30.0% and 31.3% respectively; p = 0.80). In urban area, multiple infections with HR/pHR-HPV types were detected in 13.9% and 2.7% among HIV-positive and negative women respectively (p<0.0001), whereas in rural area, multiple infections with HR/pHR-HPV types were detected in 4.7% and 3.3% of HIV-positive and negative women respectively (p = 0.56). The most prevalent HR/pHR-HPV types in HIV-positive women living in urban area were HPV 52, 51, 56, 18 and 16 types. In HIV-negative women living in urban area, the most prevalent HR/pHR-HPV types were HPV 66, 67, 18, 45 and 39 types. In HIV-positive women living in rural area, the most prevalent HR/pHR-HPV types were HPV 66, 16, 18 and 33 types. In HIV-negative women living in rural area, the most prevalent HR/pHR-HPV types were HPV 16, 66, 18, 35 and 45 types. Independent risk factors associated with cervical lesions were HPV and HIV infections. CONCLUSIONS:There is a high burden of HR and pHR-HPV infections, in particular among HIV-infected women living in urban area. The study points out the need to introduce a comprehensive cervical cancer control programme adapted to the context. This study shows that the nonavalent vaccine covers most of the HR/pHR-HPV infections in rural and urban areas among HIV-infected and uninfected women.
Project description:OBJECTIVES:To determine the impact of FDG-PET/CT in the initial staging of cervical cancer among women with and without HIV and to determine the abilities of FDG-PET/CT metabolic parameters in predicting the presence of distant metastasis. METHODS:We reviewed the FDG-PET/CT images of women with FIGO stage IB2 to IVA carcinoma of the cervix. We compared the FIGO stage before and after FDG-PET/CT. Maximum and mean standardized uptake values (SUVmax and SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of the primary lesion were determined. We compared these parameters between the HIV-infected and uninfected woman and also determined their abilities to predict the presence of distant metastasis. RESULTS:126 women, mean age 48.05 ± 11.80 years were studied. Seventy-three patients were HIV-infected. The disease was upstaged in 65 patients, 32 of which were upstaged to stage IVB. HIV-infected women were younger (43.36 ± 8.03 years versus 54.51 ± 13.12, p<0.001) and had more advanced disease (p = 0.022) compared with HIV-uninfected. In a univariate logistic regression adjusted for the FIGO stage of the disease, there were significant associations between MTV and TLG of the primary tumor and distant metastasis. SUVmax, SUVmean, MTV and TLG performed well in predicting the presence of distant metastasis with areas under the curves (AUCs) of 0.63, 0.66, 0.80 and 0.77 respectively. These performances improved after adjustment for the FIGO stage of the disease with AUCs of 0.80, 0.79, 0.84 and 0.82 for SUVmax, SUVmean, MTV and TLG respectively. CONCLUSION:Inclusion of 18F-FDG-PET/CT in the pre-therapy assessment of cervical cancer improves the accuracy of staging in about half of the patients. The metabolic parameters of the primary tumor perform well in predicting the presence of distant metastases.
Project description:Background: To synthesize published literature on the association between human immunodeficiency virus (HIV) infection and radiation therapy (RT)-related toxicities. Methods: Two electronic databases, MEDLINE and Embase, were searched to identify studies published before November 2016 comparing RT-related toxicities between HIV-infected and HIV-uninfected patients receiving RT or chemoradiation therapy (CRT) for cancer. A qualitative synthesis of included articles and organ-specific toxicities was then performed. Results: Of the 21 studies included in this review, 15 reported on anal cancer treatment, three on cervical cancer, two on Kaposi sarcoma, and one on prostate cancer. Reports in the pre-antiretroviral therapy (ART) or early ART era tended to identify increased morbidity and mortality with HIV infection. However, modern series incorporating more concurrent chemotherapy, conformal RT techniques, and ART administration result in fewer studies reporting toxicity differences in patients treated for anal and cervical cancers. When statistically significant, HIV-infected patients had higher rates of gastrointestinal toxicity with anal cancer CRT (up to 50%) and higher rates of hematologic toxicity with cervical cancer CRT (up to 31%). Of the 17 studies reporting treatment outcomes, nine suggest HIV-infected patients may have reduced local control and/or survival rates. Conclusions: Overall, RT is likely similarly tolerated between HIV-infected and HIV-uninfected patients, especially with modern RT techniques. HIV-infected patients should continue to receive established standard of care RT and CRT dosing.
Project description:BACKGROUND:Cervical cancer screening (CCS) is an important health service intervention for prevention of morbidity and mortality from invasive cervical cancer. The role of provider recommendation and referral is critical in utilization of this services particularly in settings where screening is largely opportunistic. We sought to understand how patient-reported human immunodeficiency virus (HIV) infection status is associated with provider referral in an opportunistic screening setting. METHODS:We performed a cross-sectional analysis of data on a sample of women who had received a CCS at the "Operation Stop" cervical cancer (OSCC) screening service in Jos, Nigeria over a 10-year time period (2006-2016). We used the de-identified records of women who had their first CCS to analyze the association between patient-reported HIV and likelihood of provider-referral at first CCS. We performed descriptive statistics with relevant test of association using Student t-test (t-test) for continuous variables and Pearson chi square or Fisher exact test where applicable for categorical variables. We also used a bivariable and multivariable logistic regression models to estimate the independent association of patient-reported HIV on provider referral. All statistical tests were performed using STATA version 14.1, College Station, Texas, USA. Level of statistical significance was set at 0.05. RESULTS:During the 10-year period, 14,088 women had their first CCS. The reported HIV prevalence in the population was 5.0%; 95% CI: 4.6, 5.4 (703/14,088). The median age of women who were screened was 37?years (IQR; 30-45). Women who were HIV infected received more referrals from providers compared to women who were HIV uninfected (68.7% versus 49.2%), p-value <?0.001. Similarly, we found an independent effect of patient-reported HIV infection on the likelihood for provider-referral in the screened sample (aOR?=?2.35; 95% CI: 1.95, 2.82). CONCLUSION:Our analysis supports the design of health systems that facilitates providers' engagement and provision of necessary counseling for CCS in the course of routine clinical care. The practice of offering recommendation and referrals for CCS to women at high risk of cervical cancer, such as HIV infected women should be supported.