Cancer In HIV-infected Patients Research Articles

Activation of glucocorticoid receptor signaling inhibits KSHV-induced inflammation and tumorigenesis.

Kaposi's sarcoma (KS) is the most common cancer in HIV-infected patients caused by Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Hyperinflammation is the hallmark of KS. In this study, we have shown that KSHV mediates hyperinflammation by inducing IL-1α and suppressing IL-1Ra. Mechanistically, KSHV miRNAs and vFLIP induce hyperinflammation by activating the NF-κB pathway. A common anti-inflammatory agent dexamethasone blocks KSHV-induced hyperinflammation and tumorigenesis by activating glucocorticoid receptor signaling to suppress IL-1α and induce IL-1Ra. This work has identified IL-1-mediated inflammation as a potential therapeutic target and dexamethasone as a potential therapeutic agent for KSHV-induced malignancies.

Clinical characteristics of cervical cancer in patients infected with human immunodeficiency virus

Background. Infection caused by human immunodeficiency virus (HIV) is a slowly developing anthroponosis with a long course and a variety of clinical manifestations, which finally results in acquired immunodeficiency syndrome (AIDS). Over the past 4 decades, the HIV / AIDS pandemic has been considered as one of the world’s most serious public health problems. Globally, there were approximately 38 million people living with HIV in 2022; 53 % of them were women. The number of HIV-infected patients living in Russia reaches 1,168,000. The incidence and prevalence of HIV infectionvaries across different regions of Russia. High prevalence of cervical cancer usually correlates with HIV prevalence, which is associated with the long-term and aggressive persistence of human papillomavirus (HPV) in HIV patients. HIV co-infection is believed to be the main risk factor for HPV-related precancerous lesions to the cervical epithelium and their rapid progression to invasive cancer. Aim. To analyze risk factors for poor prognosis in HIV-infected patients with HPV. Materials and methods. This study included 15 HIV-infected patients with cervical cancer treated in Novosibirsk Regional Clinical Oncology Dispensary or Federal Research and Clinical Center for Specialized Medical Care and Medical Technologies, Federal Biomedical Agency of Russia between 2016 and 2021. Results. Median age of the patients was 38 years; all of them were HPV-positive. Their viral load was >400 copies / mL and baseline CD4+ cell count ≥350 cells / mL. All patients were diagnosed with AIDS, given the presence of HPV infection. During the therapy for cervical cancer, patients also received combination antiretroviral treatment, including Lamivudine Advanced at a dose of 300 mg / day. Ten patients received comprehensive treatment, while 8 patients received chemoradiotherapy. Conclusion. Given the more aggressive course of cervical cancer in HIV-infected patients, their treatment plan should be developed by a multidisciplinary team, including an infectious disease specialist, clinical pharmacologist, radiotherapist, and gynecological oncologist. Such patients should receive maximal antitumor treatment, as well as intensive antiretroviral therapy. HIV-positive women with cervical cancer require special attention to ensure treatment completion and to optimize long-term outcomes.

Role of Antibiotic Prophylaxis and GCSF Support in Preventing Systemic Anticancer Therapy-Associated Toxicities in HIV Infected Cancer Patients: A Case Series

This is a case series report of five HIV-positive patients diagnosed with non-AIDS-defining cancer who received the combination of ART and chemotherapy. There is an increasing incidence of non-AIDS-defining cancers, such as breast cancer, lung cancer, hepatocellular carcinoma, prostate cancer, colorectal cancer, and Hodgkin’s lymphoma. The purpose of this study is to see the impact of appropriate antibiotics prophylaxis and G-CSF Support in preventing the toxicities associated with systemic anti-cancer therapy (SACT) in HIV Patients. Keywords: Human Immunodeficiency Virus, Acquired Immune Deficiency Syndrome, Anti-Retroviral Therapy, AIDS Defining Cancer, systemic anti-cancer therapy (SACT), Non-Aids Defining Cancer.

Higher Neutrophil-to-Lymphocyte Ratio (NLR) Is a Preoperative Inflammation Biomarker of Poor Prognosis in HIV-Infected Patients with Colorectal Cancer: A Retrospective Study.

The serum systemic inflammation biomarkers are known predictors of colorectal cancer (CRC) patient prognosis. However, their significance in human immunodeficiency virus (HIV)-infected patients with CRC has not been studied. To address this gap, we conducted a retrospective study to evaluate the prognostic value of preoperative systemic inflammation biomarkers in HIV-infected patients with CRC. The study enrolled 57 patients with colorectal cancer (CRC) and HIV who underwent surgery at the Shanghai Public Health Clinical Center between January 2015 and December 2021. Preoperative tests were conducted, and systemic inflammation biomarkers were measured. The patients were categorized into two groups using the optimal cut-off value. The Kaplan-Meier method and the log-rank test were used to determine overall survival (OS) and progression-free survival (PFS). Multivariate analysis was performed using the Cox proportional regression model. A time-dependent receiver operating characteristic (t-ROC) was used to compare the prognostic abilities of the biomarkers. The study included 57 HIV-infected CRC patients, with a median age of 60 and a follow-up time ranging from 3 to 86 months. Of the patients, 49 were male and 8 were female. The cumulative three-year OS and PFS rates were 55.0% and 45.0%, respectively. The optimal cut-off value for preoperative NLR was found to be 2.8, which was significantly correlated with lower CD8+ T and CD3+ T lymphocyte counts. Multivariate Cox regression analysis revealed that a low NLR was an independent predictor of better OS and PFS (OS: HR = 0.094, 95% CI: 0.02-0.45, P=0.003; PFS: HR = 0.265, 95% CI: 0.088-0.8, P=0.019). The time-dependent receiver operating characteristic (t-ROC) analysis showed that NLR was a superior systemic inflammation biomarker for predicting the prognosis of HIV-infected CRC patients throughout the observation period. The preoperative neutrophil-to-lymphocyte ratio (NLR), an easily measurable immune biomarker, may provide useful prognostic information in HIV-infected colorectal cancer (CRC) patients.

Lung cancer and HIV

BACKGROUND: People, living with HIV, have a greater chance of malignancies especially with the success of antiretroviral therapy, and non-AIDS-defining cancers have become the most common cause of death after AIDS and the most common of them is the lung cancer in developed countries.
 AIM: To research nosological characteristics of lung cancer in the context of HIV infection, HIV-associated risk factors during antiretroviral therapy and compare with global trends of this problem.
 MATERIALS AND METHODS: Retrospectively were analyzed the medical documentation of 98 patients with lung cancer and HIV-infection, who were in database and received specialized treatment in Saint Petersburg from 2008 to 2018 years.
 RESULTS: The population was dominated by patients of young (1844 years old) and middle (4559 years old) ages, 45.9% and 42.9%, respectively, and 11.2% of elderly patients (6074 years old), p 0.001, which satisfies the global data of earlier incidence of lung cancer in people living with HIV.
 Adenocarcinomas were more common histological subtype of lung cancer as in the general population (p 0.001).
 There was no static significance between high viral load and lung cancer, which can indicate the absence of a direct mechanism of HIV-carcinogenesis (90.8% of patients with low and medium viral load, p 0.001). Nevertheless, the prevalence of 4-stage of HIV infection among lung cancer patients (p 0.001) indicates a history of inflammatory diseases, including pulmonary diseases, as a result of induced immunosuppression due to CD8+-lymphocyte dysfunction and the formation of a micro-tumor environment, which can be a prognostic unfavorable factor in the occurrence of lung cancer in this group of patients , as well as indirect mechanism of viral carcinogenesis.
 The presence of elderly patients (11.2%, MAX71 years) indirectly indicates an increasing of period of life expectancy among this category of patients in Russia.
 CONCLUSION: The mechanisms of increased risk of lung cancer among HIV-infected people remain largely unclear and can be the area for active research. HIV-infected patients with lung cancer are younger than HIV-negative patients and have more advanced stages of cancer with a prevalence of adenocarcinoma type of cancer. The lung cancer prognosis of survival in HIV-infected people is much worse than that of persons without HIV-infection, but it is not fully known whether this is due to a more aggressive course of the disease, disparities in treatment, treatment resistance, or a greater risk and toxicity of therapy.

Prevalence of HPV-DNA and E6 mRNA in lung cancer of HIV-infected patients

HIV-infected individuals could be at a greater risk for developing lung cancer than the general population due to the higher prevalence in the former of human papillomavirus (HPV) in the oral cavity and higher smoking rates. Our aim was to assess HPV prevalence and E6 viral oncogene transcription in lung cancer samples from HIV-infected individuals. This was a single-center, retrospective study of a cohort of HIV-1-infected patients diagnosed with and treated for lung cancer. Pathological lung samples archived as smears or formalin-fixed paraffin-embedded blocks were subjected to HPV genotyping, detection of human p16 protein and assessment for HPV E6 mRNA expression. Lung cancer samples from 41 patients were studied, including squamous cell carcinoma (32%), adenocarcinoma (34%), non-small cell cancer (27%), and small cell cancer (7%). HPV DNA was detected in 23 out of 41 (56%, 95% CI 41–70%) of samples and high-risk (HR)-HPV types were detected in 16 out of 41 (39%, 95% CI 26–54%), HPV-16 being the most prevalent [13/16 (81.3%, 95% CI 57.0–93%]. In samples with sufficient material left: expression of p16 was detected in 3 out of 10 (30%) of HR-HPV DNA-positive tumors and in 3 out of 7 (43%) of the negative ones; and E6 mRNA was detected in 2 out of 10 (20%) of HPV-16-positive samples (squamous lung cancers). These two patients had a background of a previous HPV-related neoplasia and smoking. HR-HPV DNA detection was prevalent in lung cancers in HIV-infected patients. However, viral oncogene expression was limited to patients with previous HPV-related cancers.

Identification of unique transcriptomic signatures and key genes through RNA sequencing and integrated WGCNA and PPI network analysis in HIV infected lung cancer.

With the widespread use of highly active antiretroviral therapy (HARRT), the survival time of AIDS patients has been greatly extended. However, the incidence of lung cancer in HIV-infected patients is increasing and has become a major problem threatening the survival of AIDS patients. The aim of this study is to use Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene analysis to find possible key genes involved in HIV-infected lung cancer. In this study, using lung tissue samples from five pairs of HIV-infected lung cancer patients, second-generation sequencing was performed and transcriptomic data were obtained. A total of 132 HIV-infected lung cancer-related genes were screened out by WGCNA and differential gene expression analysis methods. Based on gene annotation analysis, these genes were mainly enriched in mitosis-related functions and pathways. In addition, in protein-protein interaction (PPI) analysis, a total of 39 hub genes were identified. Among them, five genes (ASPM, CDCA8, CENPF, CEP55, and PLK1) were present in both three hub gene lists (intersection gene, DEGs, and WCGNA module) suggesting that these five genes may become key genes involved in HIV-infected lung cancer.

Prognostic nomogram for surgery of lung cancer in HIV-infected patients.

BackgroundThis study aimed to establish an effective prognostic nomogram for surgery of lung cancer in HIV-infected patients.MethodsThe nomogram is based on a retrospective study of 51 patients who underwent lung cancer surgery at the Shanghai Public Health Clinical Center from July 2012 to November 2019. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve analysis. Internal validity was assessed using bootstrapping validation.ResultsPredictors contained in the prognostic nomogram included age, CD4+ cell count, surgery method, and pathological stage. The model displayed good discrimination with a C-index of 0.755 (95% CI: 0.715–0.795) and good calibration. A high C-index value of 0.844 was reached after internal validation.ConclusionsThe proposed nomogram may result in more-accurate prognostic predictions for surgery of lung cancer in HIV-infected patients.

Second Primary Malignancy Risk Among HIV-Uninfected and HIV-Infected Survivors of Hodgkin Lymphoma: A 30-Year Follow-up Population-Based Study

Introduction Second primary malignancy (SPM) is one of the most devastating late complications following Hodgkin lymphoma (HL) treatment. Historically, the most common SPMs in patients treated for HL are solid tumors, which are largely related to radiation exposure during initial therapy. For the last three decades, efforts to address the risk of SPM after HL therapy have focused on reducing exposure to radiation, as well as refining the approach for patients where radiation is indicated. To date, few population-based studies in the United States have quantified the burden of SPMs and evaluated the potential effect of changes in therapeutic management over time. Additionally, to our knowledge, no study has compared SPM risk between human immunodeficiency virus (HIV)-infected and HIV-uninfected HL survivors. Methods We used data from the California Cancer Registry on 21,043 patients diagnosed with primary HL between 1988 and 2015 with follow-up through 2017. We calculated standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs) and absolute excess risks (AERs) to compare SPM incidence in our HL cohort with the expected number of first primary cancer incidence in the general California population, based on patient's age at diagnosis (5-year categories), sex, calendar year (3-year intervals), cancer site, and race/ethnicity. SIRs are presented by HIV status, SPM latency, treatment era, and cancer type. P-values for trends were used to examine whether SPM risk changed over time. Findings Among 20,303 HIV-uninfected patients (median follow-up of 14.1 years), overall SPM risk was increased 1.95-fold compared with the general population (SIR=1.95, 95% CI 1.86-2.04). In 740 HIV-infected patients (median follow-up of 11.7 years), overall risk was increased 2.68-fold compared with the general population (SIR=2.68, 95% CI 2.0-3.40), translating to an 37% higher incidence of SPM in HIV-infected vs. HIV-uninfected patients. The AER (per 10,000 person-years) of SPM was 43.1 in HIV-uninfected and 76.5 in HIV-infected patients, resulting in a 33.4 excess SPM per 10,000 person-years in HL survivors with HIV. Malignancies that contributed the most to overall AER were non-Hodgkin lymphoma (NHL), female breast and lung cancers in HIV-uninfected patients; and Kaposi sarcoma, NHL, anorectal and head & neck (HNC) cancers in HIV-infected patients. Notably, among HIV-uninfected patients, the highest overall risk of SPM occurred ≥20 years after diagnosis (SIR= 2.27, 95% CI 1.99-2.58) (Figure). In contrast, the highest overall risk in HIV-infected patients was observed <2 years after diagnosis (SIR=4.42, 95% CI 2.53-7.19). Radiation used decreased from 46.9% in 1988-1996 to 29.5% in 2007-2015. Among HIV-uninfected patients, there was a trend towards decreased risk over time of overall and selected solid SPMs (lung, female breast, and gastrointestinal cancers) (Table). In an analysis restricted to HIV-uninfected patients who received radiation irrespective of chemotherapy, findings also suggested a declined risk of overall and selected solid SPMs over time: any solid (SIR=2.15 in 1988-1996 and SIR=1.30 in 2007-2015, p<0.0001), lung (SIR=3.69 in 1988-1996 and SIR=1.81 in 2007-2015, p=0.0031), and female breast (SIR=2.95 in 1988-1996 and SIR=0.63 in 2007-2015, p<0.0001). Conclusion Compared with the general population, the risk of developing a SPM following HL treatment was significantly higher among both HIV-uninfected and HIV-infected patients, with the absolute excess risk greater for those with HIV infection. There were different temporal patterns and types of SPM between HIV-uninfected and HIV-infected patients. These findings prompt the question on whether earlier and/or more intensive cancer screening should be pursued for HIV-infected survivors. The trend towards decreased risk for selected solid SPMs among HIV-uninfected patients, especially lung and female breast cancers, suggest that strategies to reduce radiation in HL survivors may be working. Despite promising trends in this group, the observation that SPM risk was highest ≥20 years after initial therapy further highlights the need for long-term surveillance and survivorship care in this at-risk population. Disclosures Rosenberg: Takeda: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Wun:Glycomimetics, Inc.: Consultancy.

Abstract 929: Transcriptomic analysis of pre-treatment tissue samples to predict clinical benefit to durvalumab in HIV-infected cancer patients

Abstract Introduction: Treatment with anti PD-1/PD-L1 antibodies has demonstrated clinical activity in different types of solid tumors, but only 20 to 30% of patients (pts) respond to these immune checkpoint inhibitors (ICIs). Therefore, predictive biomarkers of response that can assist in pt selection are urgently needed. Single biomarker expression, like PD-L1, may not provide enough information about cancer cells and the tumor microenviroment. Novel technologies, analyzing hundreds of genes at the same time, are needed to yield better predictive gene signatures of ICI response. The DURVAST trial analyzed the feasibility of durvalumab treatment in HIV-infected cancer pts, which are usually excluded from ICI clinical trials. The trial included 20 patients with different tumor types and yielded a disease control rate of 56%. Methods: Pre-ICI-treatment FFPE tumor tissue samples from 14 HIV-infected cancer pts (including 11 lung, 1 melanoma, 1 anal and 1 bladder cancer) were analyzed using the nCounter NanoString platform with the IO360 panel, including 770 genes involved in tumor biology, microenvironment and immune response. Gene expression results were correlated with clinical benefit (CB) (objective response and stable disease of more than 24 weeks by RECIST1.1 criteria), and compared to other predictive markers. Results: Exploratory analysis of pre-treatment gene expression profiles (GEPs) revealed differentially expressed genes (DEGs) between the pts with- and without CB. Panel-incorporated biological signatures related to tumor and immune activities were evaluated and some of the most DEGs (based on higher log2FC values and nominal p-values ≤0.05) were shown to be involved in cytokine and chemokine signaling. Although not significant, pts without CB tend to have lower expression of genes involved in cytokine and chemokine signaling (p = 0.097). In contrast, pts without CB tended to have a higher TGF beta signature scores (p = 0.318). When combining both signatures, we obtained an aggregated signature score that was significantly different between pts with- and without CB (p = 0.017). While the positive predictive values were the same for all tests, our signature score outperformed PD-L1 expression positivity by immunohistochemistry and PD-L1 RNA expression as predictors for clinical benefit with a two-fold higher sensitivity and negative predictive value. Conclusion: Gene expression analysis of pre-treatment tumor samples revealed distinct GEPs between HIV-infected cancer pts with- and without CB, where combined high baseline recruitment and activation of immune cells by cytokine and chemokine signaling pathways and low immunosuppressive TGF beta signaling pathways predict CB from durvalumab treatment. This predictive score outperformed other predictive markers of CB. These findings need further validation in an external and non-HIV infected pt cohort, in addition to a pt cohort treated with other ICIs. Citation Format: Jillian Wilhelmina Bracht, Maria Gonzalez-Cao, Teresa Moran, Judith Dalmau, Javier Garcia-Corbacho, Reyes Bernabe, Oscar Juan, Javier de Castro, Ana Gimenez-Capitan, Remedios Blanco, Erika Aldeguer, Sonia Rodriguez, Ana Drozdowskyj, Jordi Argilaguet, Julian Blanco, Julia Prado, Christian Brander, Jorge Carrillo, Bonaventura Clotet, Bartomeu Massuti, Mariano Provencio, Chung-Ying Huang, Clara Mayo de las Casas, Monica Garzon, Andres Felipe Cardona, Oscar Arrieta, Andreas Meyerhans, Miguel Angel Molina-Vila, Javier Martinez-Picado, Rafael Rosell. Transcriptomic analysis of pre-treatment tissue samples to predict clinical benefit to durvalumab in HIV-infected cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 929.

Abstract A043: Cancer care in people with HIV: Identifying adherence challenges to improve outcomes

Abstract Background: With improved antiretroviral therapy, people living with HIV are aging and non-AIDS-defining cancers have increasing prevalence in this population. Yet, population-based studies demonstrate that people with HIV are less likely to receive cancer treatment, which contributes to lower cancer-specific survival. Past studies have examined cancer disparities at the provider and healthy system levels, but have not explored the drivers of cancer treatment disparities from the patient’s perspective. We aimed to investigate barriers and facilitators of cancer treatment among patients living with HIV, along with perceptions of their cancer diagnosis and treatment, to inform future interventions, reduce disparities, and improve outcomes. Methods: We conducted in-depth interviews with 27 HIV-infected cancer patients to examine perceptions and care engagement in this population. We recruited equal numbers of patients who had (a) past cancer treatment, (b) were currently undergoing cancer treatment, or (c) experienced challenges with receiving or completing cancer treatment. Semi-structured interviews explored multiple topics related to HIV and cancer care, including treatment decision-making, patient-provider interactions, stigma, coping, and barriers to care. Patients were recruited until thematic saturation was reached. Results: Study participants were predominantly male (n=22, 81%) with a median age of 56 years and median annual household income of $24,000. Prevailing themes from the interviews included descriptions of the “devastating” impact of a cancer diagnosis, with a considerable dual burden of pre-existing HIV. Participants noted that having HIV added anxiety about cancer treatment, side effects, and potential treatment interactions. Among those who experienced cancer treatment adherence challenges, barriers included cancer treatment side effects, stigma, transportation difficulties, cost of care, and challenges with coping and mental health. Despite these challenges, participants generally reported having positive healthcare experiences, including compassionate providers, ease of referral, and sound communication. Several participants indicated that their past experiences of coping with HIV had prepared them to accept and address their cancer diagnosis. Conclusions: This is the first qualitative study assessing barriers and facilitators to cancer care among people living with HIV and cancer in the U.S. For many HIV-infected patients, a cancer diagnosis creates substantial added stress to an already challenging social and medical situation. Often, these stressors impact patients’ ability to complete cancer treatment. Resiliency was noted to be a key facilitator, with participants frequently citing family, friends, faith, and the healthcare system as key sources of support. Citation Format: Kelsey L Corrigan, Brandon A Knettel, Noelani Ho, Stuart Carr, Bijal Shah, Joan Cahill, Melissa Watt, Gita Suneja. Cancer care in people with HIV: Identifying adherence challenges to improve outcomes [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A043.

The safety and efficacy of immune-checkpoint inhibitor therapy in HIV infected cancer patients.

e15141 Background: The clinical utility and safety of immune-checkpoint inhibitors (ICIs) in HIV infected cancer patients has not been well studied. Methods: We conducted a systematic search of Medline and Embase from inception to December 2019 to identify case reports and case series of ICI use in HIV infected cancer patients. Data were pooled utilizing a pre-specified protocol, and descriptive statistics were employed to report findings. Results: We identified 79 cases with a mean age of 52.5 (SD 11.65), 50 of whom were males. The most common cancers were NSCLC followed by Melanoma. Nivolumab was used in 54 patients whereas Pembrolizumab was used in 15 patients, with a mean of 25.7 months to ICI initiation from cancer diagnosis, and with a mean of 1.6 prior systemic lines of chemotherapy. 72 patients were on antiretroviral therapy. The mean baseline CD4 count was 385 (227.03), with a median baseline viral load of 40 (IQR 10.75-95.39). Mean CD4 count and median viral load during ICI therapy were 344.87 (SD 209.7) and 20 (0-400), respectively. 28 patients experienced and irAE; 63.2% and 63.6% of patients who experienced a decreased or increased CD4 count while on ICI therapy experienced an irAE, respectively. 27 patients experienced progressive disease (PD); 50% of patients who experienced a decrease in their CD4 count while on ICI therapy had PD. 13 patients experienced a complete response to ICI therapy; none of the patients who had a decreased CD4 count while on ICI therapy achieved complete response to ICI therapy, whereas 25% and 33% of patients who had an increased and stable CD4 count while ICI therapy experienced a complete response to therapy. The mortality rate was 24; 75% of patients who had a decreased CD4 count on ICI therapy suffered mortality, as opposed to 37.5% and 20% of patients with increased or stable CD4 count while on ICI therapy, respectively. Conclusions: Patients with a declining CD4 count while on ICI therapy may have poor outcomes with ICI therapy. The current body of evidence is weak, and further studies are needed to reach to a strong conclusion.

Relative dose intensity and pathologic response rates in HIV-infected and HIV-uninfected breast cancer patients who received neoadjuvant chemotherapy.

e19140 Background: HIV-infected (HIV+) breast cancer patients may have significantly worse survival compared to HIV-uninfected (HIV-). If so, identifying the underlying mechanism might lead to effective interventions to reduce the disparity. Relative dose intensity (RDI) < 0.85 has been associated with worse survival outcomes in non-metastatic breast cancer patients. We aimed to determine if RDI of chemotherapy and pathologic complete response (pCR) rates were lower for HIV+ patients who received neoadjuvant chemotherapy (NAC) compared with HIV-. Methods: We conducted a prospective cohort study in newly diagnosed breast cancer patients with locally advanced disease who initiated NAC at Princess Marina Hospital in Botswana between 2/2017 and 9/2019. Clinical and treatment data were collected at baseline and at every treatment visit. Surgical pathology post-NAC was graded as pCR if there was no invasive disease in the breast or lymph nodes. RDI was calculated for each patient, with optimal RDI ≥ 0.85. Dichotomous variables were compared using Fisher’s exact and chi-squared tests; and continuous variables using rank sum tests. Results: 111 patients were enrolled, of whom 84 (75.7%) were HIV-, 26 (23.4%) HIV+ and 1 (0.9%) with unknown status who was excluded from final analysis. HIV+ patients were less likely to receive optimal RDI (0.74 vs. 0.88; p = 0.03). Of the 110 patients 15 (13.6%) were still receiving chemotherapy; 22 (20%) prematurely discontinued chemotherapy of whom 11 (10%) received surgery; 7 (6.4%) completed chemotherapy but had no surgery. 77 (70%) completed surgery which included 11 (10%) with no pathology reports available, 3 (2.7%) inadequate surgical specimens and 63 (57.3%) complete pathology results included in pCR analysis: 1/13 (7.7%) HIV+ patients had a pCR compared to 12/50 (24%) in HIV-(p = 0.27). Conclusions: HIV+ patients were significantly more likely to receive inadequate neoadjuvant chemotherapy dose intensity, and trended towards a lower pCR in this small cohort, which may contribute to adverse treatment outcomes. Further study needed to validate high rate of treatment discontinuation and specific risk factors to inform targeted interventions to improve therapy delivery.

Cancer spectrum in HIV-infected patients: A zonal hospital experience in Tanzania

Although the burden of human immunodeficiency virus (HIV) infection in Tanzania is high, limited data are available on cancers in HIV-infected patients. We aimed to determine the spectrum and prevalence of cancers in HIV-infected patients attending care at a zonal hospital in Tanzania. Clinical records of HIV-infected patients from 2009 to 2019 were identified and retrospectively reviewed. A total of 3398 HIV-infected patients were recruited with median age of 37 years. Cancer was diagnosed in 9% of the patients after enrollment into HIV clinical care, with an increasing prevalence from 7.2% between years 2009 and 2013 to 8.6% between years 2017 and 2019 (p-value <0.0001). Majority (89.2%) were on antiretroviral therapy (ART) during the time of cancer diagnosis. The proportions of acquired immunodeficiency syndrome (AIDS)-defining cancers and non-AIDS defining cancers were 28% and 72% respectively. Kaposi's sarcoma was the most common (13.2%) AIDS-defining cancer while esophageal cancer was the most common (11.1%) non-AIDS defining cancer. The median duration of time from HIV infection to cancer diagnosis was 715 days (IQR: 98-2570). The median CD4+T-cell count was 318(IQR 159-690) cells/µl at the time of cancer diagnosis and 40.7% of the patients had advanced immunosuppression with CD4 count less than 200 cells/µl at the time of cancer diagnosis. Non-AIDS defining cancers were much more common than AIDS-defining cancers suggesting increased longevity due to ART access. The prevalence of cancer among HIV-infected patients was 9% with an increasing trend over time; highlighting the importance of promoting cancer screening in this vulnerable population and implementation of vaccinations programs for liver and cervical cancers as well as tobacco control policies for smoking-related cancers.

Low prevalence of symptomatic thyroid diseases and thyroid cancers in HIV-infected patients

Thyroid diseases (TDs) have been widely associated with HIV infection. However, data about TDs prevalence and distribution are controversial, and few published studies are available. The aim of our study was to assess prevalence and risk factors of symptomatic thyroid disturbances, including thyroid cancers, in a large cohort of HIV-infected patients. A retrospective cohort study was performed at the Department of Infectious and Tropical Diseases of the University of Brescia, Italy, in the period 2005–2017. We identified all HIV-positive patients with a diagnosis of symptomatic TD in the electronic database of our Department (HIVeDB); we also operated a record-linkage between our data and the Health Protection Agency database (HPADB) of Brescia Province. Multivariate logistic regression analysis was used to determine risk factors associated with TDs onset; an incidence rate analysis was also performed. During the study period, 6343 HIV-infected patients have been followed at our Department; 123 received a diagnosis of symptomatic TD (1.94% of the entire cohort). In the TDs group, almost half of patients were females (n = 59, 48%), mean age was 47.15 years (SD: 11.56). At TD diagnosis, mean T CD4+ cell count was 491 cell/uL and most patients showed undetectable HIV-RNA (n = 117, 95.12%). Among them, 81 patients were found to have hypothyroidism (63 with Hashimoto’s thyroiditis), 21 hyperthyroidism (17 suffered from Graves’ disease), while 11 subjects were diagnosed with a primitive thyroid cancer. Papillary thyroid cancer was the most frequent histotype (n = 7, 63.63%), followed by medullary (n = 2, 18.18%) and follicular thyroid cancer (n = 1, 9.1%). Male gender was a protective factor for TDs development, especially for hypothyroidism (p < 0.001); age emerged as a variable associated with both hypothyroidism (p = 0.03) and thyroid cancer (p = 0.03), while CD4+ cell nadir <200 cell/mm3 was associated with symptomatic hyperthyroidism (p = 0.005). To conclude, symptomatic thyroid dysfunctions rate in well-treated HIV-infected patients is low. Age and gender are crucial elements in the onset of thyroid abnormalities, together with T CD4+ cell nadir. Interestingly, medullary thyroid cancer seems to be much more frequent in HIV-infected patients compared to the general population.

Report of clinico-pathological features of breast cancer in HIV-infected and uninfected women in Botswana

BackgroundTo characterize the clinico-pathological features including estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu (HER2) expression in breast cancers in Botswana, and to compare them by HIV status.MethodsThis was a retrospective study using data from the National Health Laboratory and Diagnofirm Medical Laboratory in Gaborone from January 1, 2011 to December 31, 2015. Clinico-pathological details of patients were abstracted from electronic medical records.ResultsA total of 384 unique breast cancer reports met our inclusion criteria. Of the patients with known HIV status, 42.7% (50/117) were HIV-infected. Median age at the time of breast cancer diagnosis was 54 years (IQR 44–66 years). HIV-infected individuals were more likely to be diagnosed before age 50 years compared to HIV-uninfected individuals (68.2% vs 23.8%, p < 0.001). The majority of patients (68.6%, 35/51) presented with stage III at diagnosis. Stage IV disease was not presented because of the lack of data in pathology records surveyed, and additionally these patients may not present to clinic if the disease is advanced. Overall, 68.9% (151/219) of tumors were ER+ or PR+ and 16.0% (35/219) were HER2+. ER+ or PR+ or both, and HER2- was the most prevalent profile (62.6%, 132/211), followed by triple negative (ER−/PR−/HER2-, 21.3%, 45/211), ER+ or PR+ or both, and HER2+, (9.0%, 19/211) and ER−/PR−/HER2+ (7.1%, 15/211). There was no significant difference in receptor status noted between HIV-infected and HIV-uninfected individuals.ConclusionsMajority of breast cancer patients in Botswana present with advanced disease (stage III) at diagnosis and hormone receptor positive disease. HIV-infected breast cancer patients tended to present at a younger age compared to HIV-uninfected patients. HIV status does not appear to be associated with the distribution of receptor status in breast cancers in Botswana.

Risk of Invasive Anal Cancer in HIV-Infected Patients With High-Grade Anal Dysplasia: A Population-Based Cohort Study.

The progression rate and predictors of anal dysplastic lesions to squamous cell carcinoma of the anus remain unclear. Characterizing these parameters may help refine anal cancer screening guidelines. This study aimed to determine the rate of progression of high-grade anal dysplasia to invasive carcinoma in HIV-infected persons. Using the Surveillance, Epidemiology, and End Results database linked to Medicare claims from 2000 to 2011, we identified HIV-infected subjects with incident anal intraepithelial neoplasia III. To estimate the rate of progression of anal intraepithelial neoplasia III to invasive cancer, we calculated the cumulative incidence of anal cancer in this cohort. We then fitted Poisson models to evaluate the potential risk factors for incident anal cancer. This is a population-based study. Included were 592 HIV-infected subjects with incident anal intraepithelial neoplasia III. The primary outcome measured was incident squamous cell carcinoma of the anus. Study subjects were largely male (95%) with a median age of 45.7 years. Within the median follow-up period of 69 months, 33 subjects progressed to anal cancer. The incidence of anal cancer was 1.2% (95% CI, 0.7%-2.5%) and 5.7% (95% CI, 4.0%-8.1%) at 1 and 5 years, following a diagnosis of anal intraepithelial neoplasia III. Risk of progression did not differ by anal intraepithelial neoplasia III treatment status. On unadjusted analysis, black race (p = 0.02) and a history of anogenital condylomata (p = 0.03) were associated with an increased risk of anal cancer incidence, whereas prior anal cytology screening was associated with a decreased risk (p = 0.04). The identification of some incident cancer episodes used surrogate measures. In our population-based cohort of HIV-infected subjects with long-term follow-up, the risk of progression from anal intraepithelial neoplasia III to anal squamous cell carcinoma was higher than reported in other studies and was not associated with the receipt of anal intraepithelial neoplasia III treatment. See Video Abstract at http://links.lww.com/DCR/A933.

Abstract PL04-02: HIV malignancies: From despair to gene therapy

Abstract HIV antiretroviral therapy has dramatically decreased the relative risk of HIV associated cancer. Nonetheless, the longevity of people living with HIV and the ongoing exposure to a variety of interconnected risk factors results in an increased life time risk of cancer compared with the general population. This includes AIDS defining and non-AIDS defining cancers. Risks increase during breaks in antiviral therapy and reinforce the recommendation that patients should avoid breaks in therapy. The non-HIV factors which interplay in carcinogenesis include immune dysregulation, immunosuppression, viral co-infections, and lifestyle habits that are more prevalent among people living with HIV. In this lecture we will explore these issues as they relate to non-Hodgkin lymphoma, Hodgkin lymphoma, Kaposi sarcoma, anal and cervical cancer, lung cancer and hepatocellular carcinoma. We will outline fundamental principles of therapy with an emphasis on the much-improved prognosis compared to the era before antiviral therapy. We will explore some of the current research questions including the incorporation of lentivirus vectors carrying anti-HIV genes into hematopoietic stem cells. We will also review the impact of anti-HIV bias on cancer clinical trials and the response of the American Society of Clinical Oncology to broaden eligibility in those trials. The approach to cancer in HIV infected patients has evolved dramatically since the recognition of AIDS and patients can now benefit from more definitive approaches to malignancy with far superior outcomes. Citation Format: Ariela Noy. HIV malignancies: From despair to gene therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr PL04-02.

Risk and Predictors of Esophageal and Stomach Cancers in HIV-Infected Veterans: A Matched Cohort Study.

To evaluate the risks of esophageal and stomach carcinomas in people living with HIV (PLWH) compared with the general population and risk factors for these cancers in PLWH. Retrospective cohort study in the Veterans Health Administration. We compared incidence rates for esophageal and stomach cancers in 44,075 HIV-infected male veterans with those in a matched HIV-uninfected cohort (N = 157,705; 4:1 matched on age and HIV-index date). We used Cox regression models to estimate Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with HIV infection and for cancer risk factors in PLWH. In unadjusted models, HIV infection was associated with increased risks of esophageal squamous cell carcinoma (ESCC; HR, 2.21; 95% CI: 1.47 to 3.13) and gastric cardia cancer (HR, 1.69; 95% CI: 1.00 to 2.85) but associated with lower risk of esophageal adenocarcinoma (EAC; HR, 0.48; 95% CI: 0.31 to 0.74). After adjusting for age, race/ethnicity, smoking and alcohol use, HIV infection remained statistically significantly associated with elevated risk for ESCC [adjusted hazard ratio (aHR), 1.58; 95% CI: 1.02 to 2.47], especially among HIV-infected patients with CD4 count ≤200 (aHR, 2.20; 95% CI: 1.35 to 3.60). HIV infection was not associated with risks of EAC (aHR, 0.82; 95% CI: 0.53 to 1.26), gastric cardia (aHR, 0.80; 95% CI: 0.33 to 1.94), or noncardia (aHR, 1.06; 95% CI: 0.61 to 1.84) cancers. Risk factors for these cancers in HIV-infected patients were otherwise similar to those in general population (eg, Helicobacter pylori for gastric noncardia cancer). HIV-infected individuals with low CD4 count are at highest risk for ESCC, but HIV infection was not independently associated with EAC or gastric cancer after adjusting for confounders.

HIV-infected patients with opportunistic pulmonary infections misdiagnosed as lung cancers: the clinicoradiologic features and initial application of CT radiomics.

To characterize clinicoradiologic and radiomic features for identifying opportunistic pulmonary infections (OPIs) misdiagnosed as lung cancers in patients with human immunodeficiency virus (HIV). Twenty-four HIV-infected patients who were misdiagnosed with lung cancers on CT images and had OPIs confirmed by pathological examination or integration of clinical and laboratory findings and 49 HIV-infected patients with lung cancers confirmed pathologically were included. Semiautomated segmentation of the lesion was implemented with an in-house software. The lesion boundary was adjusted manually by radiologists. A total of 99 nonenhanced-CT-based radiomic features were then extracted with PyRadiomics. The clinicoradiologic and radiomic features were compared between the OPI and cancer groups. In the OPI group, 19 patients (79.2%) had tuberculosis (TB) infections, 2 (8.3%) had nontuberculosis mycobacterium (NTM) infections, 2 (8.3%) had cryptococcus infections and 1 (4.2%) had a mixed infection of TB and NTM. There were significant differences in age, proportion of smokers, smoking index, highly active antiretroviral therapy (HAART) duration, CD4+ counts and CD4+/CD8+ ratio between the two groups (P=0.000, 0.012, 0.007, 0.002, 0.000, and 0.000, respectively). In peripheral-type lesions, the presence of pleural indentation was less common, and the presence of satellite lesions was more common in the OPI group (P=0.016 and 0.020, respectively). Four radiomic parameters of central-type lesions were significantly different, including large dependence high gray level emphasis (LDHGLE), skewness, inverse difference normalized (IDN) and kurtosis (P=0.008, 0.017, 0.017, and 0.017, respectively). However, neither CT features of central-type lesions nor radiomic parameters of peripheral-type lesions were significantly different between the two groups. Clinicoradiologic features together with radiomics may help identify OPIs mimicking lung cancers in HIV-infected patients.