Lung Cancer In HIV-infected Patients Research Articles

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.

Lung cancer in HIV-infected patients in the combination antiretroviral treatment era.

The advent of combination antiretroviral treatment (cART) has been followed by a decrease in HIV-associated morbidity and mortality, but also by an apparent increase in the incidence of non-AIDS-defining cancers (NADCs). The risk of lung cancer is substantially higher in HIV-infected patients than in the general population, in part due to aging and tobacco use, and it is the most frequent NADC. The management of lung cancer in HIV-infected patients has some peculiarities that need to be taken into account. This review focuses on the epidemiology, risk factors, and clinical management of lung cancer in HIV-infected patients. In addition, screening tools and future perspectives are also discussed.

Lung cancer in HIV-infected patients and the role of targeted therapy.

Lung cancer is one of the most common malignancies in HIV-infected patients. Prevalence and mortality outcomes are higher in HIV-infected populations than in noninfected patients. There are several oral agents available for patients who harbor specific mutations, but little is known about mutations and affected pathways in HIV-infected patients with lung cancer. Recent trials have facilitated the inclusion of HIV-infected patients in clinical trials, but the population is remains underrepresented in oncology trials. Here, we review the literature on lung cancer in HIV-infected patients, and discuss common mutations in lung cancer and HIV-infected patients, the role of mutational analysis, and the potential role of targeted therapy in the treatment of lung cancer in HIV-infected populations.

Advanced large cell lung tumor with neuroendocrine differentiation in an HIV positive patient.

Sir, Human immunodeficiency virus (HIV) infection is well known to be associated with several cancers and respiratory complications. Lung cancer is one of the most common cancers in HIV-infected individuals. We report the case of a HIV-positive smoker male who was admitted with fever, cough and right-sided pleuritic chest pain. Imaging studies revealed the presence of right-sided pleural effusion with multiple pleural based nodules and right lower lobe mass. Histopathologic examination of the tissue showed large cell lung tumor with neuroendocrine differentiation (LCNEC). LCNEC is an extremely rare lung cancer with this being the only case reported in an HIV-positive patient. A 49-year-old HIV-positive male smoker on antiretroviral therapy (tenofovir, emtricitabine and efavirenz) with good medication compliance presented with cough and progressively worsening right-sided pleuritic chest pain for 2 weeks. He also stated having loss of appetite and 23 kg weight loss over the last 2 months. He denied having any hemoptysis, abdominal or neurologic symptoms at presentation. There was no history of preexisting lung disease, diabetes, illicit drug abuse or lung infections. Fifteen days ago his CD4 cell count was 750/μl with an undetectable viral load. Clinical examination showed stable vitals. Chest examination revealed decreased breath sounds on the right with decreased tactile vocal fremitus over the right middle and lower lung fields. Cardiovascular, abdominal, neurologic and skin examination failed to show any abnormality. Initial laboratory tests including complete blood counts and serum chemistries were within normal limits. Chest radiograph revealed a right-sided effusion without any mediastinal shift. Chest computed tomography (CT) scan confirmed the presence of a large right-sided pleural effusion with multiple pleural based soft tissue densities and a right lower lobe mass [Figure 1].Figure 1: CT chest showing right-sided effusion with pleural-based soft tissue (white arrow) density and a right lower lobe mass (red arrow)Thoracocentesis showed an exudative hemorrhagic fluid with no malignant cells on cytologic examination. The patient underwent video-assisted thoracoscopic examination (VATS) with biopsy of the pleural-based soft tissue mass. Histopathologic examination of the tissue showed large cells with organoid growth pattern, high mitotic index and areas of necrosis [Figure 2]. The neuroendocrine phenotype was confirmed by the presence of positive staining for synaptophysin and chromogranin A.Figure 2: Histopathologic examination of pleural masses showing large cell tumor of lung originDue to pleural involvement, the patient was diagnosed with a stage IV large cell lung cancer with neuroendocrine differentiation. The patient agreed for a trial of chemotherapy with carboplatin and etoposide. Initial work-up for metastatic spread of the disease failed to show any extra-thoracic involvement. Over the course of next 9 months, the patient's condition worsened with metastatic involvement of the liver and brain, ultimately leading to his death. Lung cancer, the leading cause of cancer-related deaths in the general population is the third most common malignancy in HIV-infected individuals, preceded only by Kaposi's sarcoma and non-Hodgkin's lymphoma.[123] The most common histologic variants of non-small cell lung cancer seen in the patients infected with HIV are adenocarcinoma (31-50%), squamous cell carcinoma (19-36%) and large cell carcinoma (9-19%).[45] Large cell lung tumors with neuroendocrine differentiation make up about 1.6-3.1% of all lung cancers in the general population.[6] The association of LCNEC with HIV infection is even rarer. Extensive literature review failed to reveal any case report of LCNEC in an individual infected with HIV. HIV infection is a well-known independent risk factor for lung cancer. The exact pathophysiology for increased incidence of lung cancer in the patients with HIV infection is unclear. HIV patients are diagnosed with lung cancer at earlier age (average age of diagnosis: 46 years) compared to HIV-negative patients who develop lung cancer.[56] HIV-positive patients with lung cancer are also thought to have more advanced stages of lung cancer at the time of diagnosis with severe pulmonary symptoms. The diagnostic and treatment approach to lung cancer in HIV-infected patients is similar to those with lung cancer without co-infection with HIV. In conclusion, HIV infection acts as an independent risk factor for lung cancer, with adenocarcinoma being the most common histopathologic variant and LCNEC being extremely rare. The diagnostic and treatment approach in the patients with lung cancer remains unaffected by their HIV status. The only area of concern is the potential interaction between certain chemotherapeutic agents and antiretroviral medications. The worsened outcomes and poorer prognosis in the lung cancer patients with HIV infection as compared to those without HIV infection are attributed to the weakened immune system in the former. ACKNOWLEDGEMENT We thank Dr. Sudheer Chauhan and Dr. Maximo Mora for their support and contribution in the diagnosis and management of the patient.

Current questions in HIV-associated lung cancer

In this review, we explore current questions regarding risk factors contributing to frequent and early onset of lung cancer among populations with HIV infection, treatment, and outcomes of lung cancer in HIV-infected patients as well as challenges in a newly evolving era of lung cancer screening. Lung cancer, seen in three-fold excess in HIV-infected populations, has become the most common non-AIDS defining malignancy in the highly active antiretroviral therapy era. HIV-associated lung cancer appears to be associated with young age at diagnosis, cigarette smoking, advanced stage at presentation, and a more aggressive clinical course. There is no unified explanation for these observations, and aside from traditional risk factors, HIV-related immunosuppression and biological differences might play a role. In addition to smoking cessation interventions, screening and early cancer detection in HIV-infected populations are of high clinical importance, although evidence supporting lung cancer screening in this particularly high-risk subset is currently lacking, as are prospective studies of lung cancer therapy. There is an urgent need for prospective clinical trials in HIV-associated lung cancer to improve understanding of lung cancer pathogenesis and to optimize patient care. Several clinical trials are in progress to address questions in cancer biology, screening, and treatment for this significant cause of mortality in persons with HIV infection.

Lung cancer in HIV-infected patients

Our objective was to determine the prevalence and characteristics of lung cancer (LC) in HIV patients and compare them with LC patients from the general population. All HIV patients diagnosed at three hospitals in Malaga (southern Spain) who developed LC during January 1989-June 2012 were reviewed. They were compared with a sample of patients with LC taken from the Pneumology and Oncology Department of the Hospital Virgen de le Victoria (Malaga) during the same period. Of the 4721 HIV patients (83% men) followed-up during the study period, 61 (1.29%) developed LC: 82% were men, mean age 48 years, all except two were smokers, 47.5% had a prior lung infection, and the median CD4 count was 237 cells/mm(3). Forty (65.5%) patients were on antiretroviral therapy at LC diagnosis (70% had an undetectable viral load). The HIV-negative group was older at diagnosis, contained fewer active smokers, had a greater frequency of the squamous cell carcinoma histological subtype and fewer cases of adenocarcinoma. Presentation was advanced in both groups and the median survival of HIV patients was three months. LC is a common tumour in HIV patients. It affects men and women equally, with a history of smoking and often a prior opportunistic lung disease. Affected patients are often immunosuppressed and have had an AIDS-related diagnosis.

Incidence and risk of lung cancer in HIV-infected patients

Lung cancer is one of the most common non-AIDS-defining malignancies among HIV-infected patients. The incidence of lung cancer has significantly increased in the HIV-positive population in recent years. The purpose of this study was to summarize the incidence and risk of lung cancer in published population-based studies of people with HIV/AIDS. Published literature from PubMed, Embase, the Web of Science, and Google Scholar was retrieved. Sixty-five publications were selected and assessed for the following parameters: research coverage and location; continent; study period; duration of follow-up; lung cancer cases; HIV cases; incidence rate; and overall SIR or adjusted IRR. In addition, the risk of lung cancer was compared based on age, gender, HIV exposure category, CD4 count, and periods with highly active antiretroviral therapy (HAART). Lung cancer risk was greater among HIV-infected individuals compared with the general population. SIRs or adjusted IRRs were 1.5-3.4 in Europe, 0.7-6.9 in the USA, and 5.0 in Africa. Most, but not all studies did not observe a significant change in the incidence and risk of lung cancer between the pre-HAART and HAART eras. In most studies, the risk of lung cancer was higher among women, younger individuals, and injection drug users (IDUs), but the incidence of lung cancer was higher among men and the elderly. No significant trend in lung cancer risk across CD4 cell count categories was reported among the selected articles. Our study suggests an increase in the incidence and risk of lung cancer in HIV/AIDS population is worldwide. The effect of HAART on the incidence and risk of lung cancer is in dispute. The risk of lung cancer based on gender differences, especially among females, as well as IDUs, requires further investigation.

Epidemic of Lung Cancer in Patients With HIV Infection

The survival of patients with HIV infection has improved dramatically over the past 20 years, largely owing to a significant reduction in opportunistic infections and AIDs-defining malignancies, such as lymphoma and Kaposi sarcoma. However, with improved survival, patients with HIV are experiencing morbidity and mortality from other (non-AIDs-defining) complications, such as solid organ malignancies. Of these, the leading cause of mortality in the HIV-infected population is lung cancer, accounting for nearly 30% of all cancer deaths and 10% of all non-HIV-related deaths. Importantly, the average age of onset of lung cancer in the HIV-infected population is 25 to 30 years earlier than that in the general population and at lower exposure to cigarette smoke. This article provides an overview of the epidemiology of lung cancer in the HIV-infected population and discusses some of the important risk factors and pathways that may enhance the risk of lung cancer in this population.

Lung cancer in HIV-infected patients: the experience in Brescia from 1999 to 2009

Lung cancer (LC) is the most common cancer among the non AIDS-defining malignancies in the highly active antiretroviral therapy (HAART) era. We described 23 HIV infected patients with a LC diagnosis followed in the Clinic of Tropical and Infectious Diseases of Brescia during the period of 1999-2009. All of these patients except two (n = 21, 91.3%) were cigarette smokers and all had at least one risk factor for developing cancer of the lung, or predisposing comorbidities, such as a COPD (chronic obstructive pulmonary disease) or a previous pneumonia. The median age at LC diagnosis was 53.6 years (range 21.2-71.4 years). Adenocarcinoma and squamous cell carcinoma were diagnosed in 10 cases (43.5%) respectively. In 21 subjects (91.3%) cancer was detected at stage IV with metastases. The median survival was 5.95 months. Greater intervention focused on the cessation of smoking is necessary, as well as the implementation of closer screening policies, especially in HIV-positive subjects with LC risk factors.

HIV as an independent risk factor for incident lung cancer

It is unclear whether the elevated rate of lung cancer among HIV-infected persons is due to biological effects of HIV, surveillance bias, or excess smoking. We compared the incidence of lung cancer between HIV-infected and demographically similar HIV-uninfected patients, accounting for smoking and stage of lung cancer at diagnosis. Data from the Veterans Aging Cohort Study Virtual Cohort were linked to data from the Veterans Affairs Central Cancer Registry, resulting in an analytic cohort of 37,294 HIV-infected patients and 75,750 uninfected patients. We calculated incidence rates of pathologically confirmed lung cancer by dividing numbers of cases by numbers of person-years at risk. We used Poisson regression to determine incidence rate ratios (IRRs), adjusting for age, sex, race/ethnicity, smoking prevalence, previous bacterial pneumonia, and chronic obstructive pulmonary disease. The incidence rate of lung cancer in HIV-infected patients was 204 cases per 100,000 person-years [95% confidence interval (CI) 167-249] and among uninfected patients was 119 cases per 100,000 person-years (95% CI 110-129). The IRR of lung cancer associated with HIV infection remained significant after multivariable adjustment (IRR 1.7; 95% CI 1.5-1.9). Lung cancer stage at presentation did not differ between HIV-infected and uninfected patients. In our cohort of demographically similar HIV-infected and uninfected patients, HIV infection was an independent risk factor for lung cancer after controlling for potential confounders including smoking. The similar stage distribution between the two groups indicated that surveillance bias was an unlikely explanation for this finding.

Lung Cancer: An Emerging Epidemic in the human immunodeficiency virus-Infected Population

As opportunistic infections and acquired immune deficiency syndrome (AIDS)-related cancers are decreasing in the human immunodeficiency virus (HIV)-infected population since the advent of highly active antiretroviral therapy (HAART), new causes of morbidity and mortality are emerging, such as cardiovascular diseases and non-AIDSdefining cancers (NADCs).1–4 The general aging of the HIV-infected populations in resource-rich settings, because of an increasing life expectancy approaching that of the general population in some successfully treated groups, also explains this shift to nonopportunistic diseases.5,6 In resource-rich setting studies, lung cancer has the highest incidence rate of all NADCs,3,7 and despite the advent of HAART, its incidence rate remains increased in comparison with the non-HIV-infected population. The review by Pakkala and Ramalingam8 focuses on epidemiological, clinical, and management of lung cancers in HIV-infected patients and helps us to disentangle future perspectives of research. This review underscores the increased incidence and the clinical particularities of lung cancer in the HIV-infected population in comparison with the HIV-negative counterparts, including an increased proportion of advanced stages III and IV and young age at diagnosis, as well as its dismal prognosis. The reasons of an increased incidence in the rate of lung cancer in the HIV-infected population in comparison with their uninfected counterparts have been approached in this review. One factor is the increased prevalence of smoking in the HIV-infected populations: in different observational cohorts, the rate of chronic smoking history has been evaluated as more than 50%, outnumbering the proportion of smokers in the general population.9 However, this characteristic, although essential in the triggering of lung cancer in the HIV-infected population, is insufficient to completely explain the increased incidence, because multivariate studies adjusted on smoking status, age, and gender have found a persistent increased risk of lung cancer.10–12 The most important factor explaining increased incidence of lung cancer in HIVinfected patients is probably the intensity and duration of immune deficiency. Grulich et al.13 found a significantly and similar standardized increased ratio in lung, trachea, and bronchus cancer in comparison with the general population in HIV-infected population and solid organ transplant recipients in a meta-analysis of population-based cohorts (respective standardized increased ratio of 2.72 [1.91–3.87] and 2.18 [1.85–2.57]), immunodeficiency being the only common factor between these two populations. It is now well established that the intensity of CD4 depletion is an important factor. The Clinical Epidemiology Group of the FHDH-ANRS CO4 cohort correlated risk of lung cancer with the latest levels of CD4 strata7 in more than 52,278 subjects and showed a progressive increase of incidence for each lower strata of CD4: odd ratios ranged from 8.5 (4.3–16.7) for the CD4 strata of 50 cells/ l to 2.2 (1.3–3.6) for the CD4 strata of 350 to 500 cells/ l

Lung Cancer in HIV-Infected Patients: The Experience of an Urban Clinic

Lung cancer is one of the most common non-AIDS-defining malignancies among HIV-infected patients. Recent studies suggest that lung cancer risk is 3 to 4 times higher in HIV-infected patients than in uninfected persons after adjusting for other factors such as smoking intensity and duration. A retrospective chart review (2002-2009) was conducted in our institution. An abstraction form was used to compile data that included demographics, T-cell count, and viral loads before and at the time of diagnosis, comordibities, smoking, and use of alcohol and drugs. A total of 16 patients were found. Of these, 11 (69%) patients were male and 5 (31%) female. The average age at diagnosis was 49 years (range 36-54). The Majority of patients were African American (90%). Their average CD4 counts before and at the time of diagnoses were 241 and 211 cells/mm( 3), respectively. Their viral loads before and at the time of diagnosis ranged from <48 to 437 000 and <48 to 590 760 copies/mL, respectively. Adenocarcinoma was found in 67% of cases. The majority of cases (85%) were detected at advanced stages (IIIB or IV). Smoking was found in 100% of cases (average of 15-20 pack/year history), alcohol use in 70% of cases, and drug abuse in 50%. Lung cancer is very common in HIV-infected populations. It tends to occur at a young age, and it is usually diagnosed at very advanced stages (IIIB or IV). The main risk factors found in our study were extensive smoking history, young age, male sex, and potentially prolonged immunosuppression. Based on these results, an attempt to construct a high-risk group index might not be appropriate due to the limited number of cases studied and the need for further evaluation of the length of immunosuppression and the real impact of HIV RNA viral load in the development of lung cancer.

Lung Cancer in HIV-Infected Patients in the Era of Highly Active Antiretroviral Therapy

Infection with the human immunodeficiency virus (HIV) and lung cancer represent two problems beginning in the 20th century that are of epidemic proportions. By the end of the 20th century, therapeutic programs of modest efficacy had been developed for both. Because both HIV infection and lung cancer are common, it is not surprising that a number of patients would be afflicted with both diseases simultaneously. There is a very limited literature regarding the treatment and outcome of patients with both diseases, particularly since the advent of highly active antiretroviral therapy (HAART) for HIV infection. We retrospectively reviewed our tumor registry to ascertain cases with concurrent lung cancer and HIV diagnoses since 1996, at the advent of HAART. Twenty-nine patients were identified at the University of Maryland, and five additional cases from an affiliated institution were identified. Thirty patients had non-small cell lung cancer, and four patients had small cell lung cancer. Of the 30 patients with non-small cell lung cancer, 27 had stage IIIb/IV disease and were analyzed for outcome on the basis of CD4 counts and HAART therapy. Patients with CD4 counts >200 or those on HAART had numerically, though not statistically, superior survival. Patients were able to receive standard chemotherapy regimens, and the overall survival was 5.2 months. This single-institution analysis appears to indicate that there is an increasing incidence of patients with lung cancer and HIV infection. Patients with advanced NSCLC who are HIV positive with CD4 counts >200 can be treated with chemotherapy and demonstrate survival comparable to that of patients without HIV infection.

Delayed Diagnosis and Elevated Mortality in an Urban Population With HIV and Lung Cancer

Lung cancer is more common in HIV-infected patients than in the general population. We examined how effectively lung cancer was being diagnosed in our HIV-infected patients. Retrospective study assessing clinical diagnosis of lung cancer in HIV-infected patients at Johns Hopkins Hospital between 1986 and 2004. Ninety-two patients were identified. Compared to HIV-indeterminate patients (n=4973), HIV-infected individuals were younger with more advanced cancer. CD4 counts and HIV-1 RNA levels indicated preserved immune function. Mortality was higher in HIV-infected patients, with 92% dying of lung cancer (hazard ratio, 1.57; 95% confidence interval, 1.25-1.96), compared to HIV-uninfected patients. Advanced stage and black race were associated with worse survival. After adjustment for these factors, HIV infection was not associated with increased mortality (hazard ratio, 1.04; 95% confidence interval, 0.83-1.32). Of 32 patients followed in our HIV clinic, 60% of chest radiographs had no evidence of neoplasm within 1 year of diagnosis compared to only 1 (4%) of 28 chest computed tomography scans. Nonspecific infiltrates were observed in 9 patients in the same area that cancer was subsequently diagnosed. HIV-infected lung cancer patients have shortened survival mainly due to advanced stage. Low clinical suspicion and overreliance on chest radiographs hindered earlier detection. Aggressive follow-up of nonspecific pulmonary infiltrates in these patients is warranted.

Lung cancer in HIV-infected patients: a one-year experience.

The relative incidence and rate of lung cancer in HIV-infected patients compared with the general US population has been a source of controversy. We sought to establish these parameters in a cohort of 2616 HIV-infected patients. Tumour type, stage of disease, patient demographics and immune parameters including viral loads were ascertained. An annual rate of 191 cases/100,000 population was found, which is 3.01 times greater (95% confidence interval [CI]=1.3-7.0) when compared with the general US population and 7.4 times the rate in US males between ages 35 and 54 (95% CI=3.1-17.8). Three patients had CD4 counts greater than 200 cells/mm3 at diagnosis and 2 had undetectable viral loads. The mean age was 44 years and all had advanced disease and short survival. In conclusion, the incidence of primary lung cancer was increased in this cohort of HIV-infected patients and occurred over a wide range of immunosuppression and viral replication.

Adénocarcinomes d'origine inconnue à manifestation thoracique et VIH : à propos de quatre cas

Adenocarcinomas of unknown primary site with thoracic localization and HIV : four case reports. Introduction. — Non AIDS-defining cancer would have increased in HIV-patients as suggested by numerous studies. Four cases of adenocarcinoma of unknown primary site with thoracic localization that occurred in HIV-infected patients are described. Exegesis. — To date, there have been no published data about carcinomas of unknown primary site relating to HIV-infected patients; however, immunodepression could promote them. Carcinomas of unknown primary site account for 0.5 to 10% of all cancers in general population. Primary carcinoma is identified in approximately one third of the cases and often corresponds to lung cancer in case of sus-diaphragmatic metastasis, particularly in case of pleural metastasis. Lung cancer in HIV-infected patients affects mostly youg men who smoke and are often intravenous drug addicts. Adenocarcinoma is the most common histological type of cancer. Conclusion. — Further studies of lung cancer in HIV-infected patients will help evaluate their frequency. In case of increasing frequency, lung cancer should then be included in AIDS-defining cancers.