Cancer In HIV-infected Individuals Research Articles

Immune Activation and Microbial Translocation as Prognostic Biomarkers for AIDS-Related Non-Hodgkin Lymphoma in the AMC-034 Study.

AIDS-related non-Hodgkin lymphoma (ARL) is the most common cancer in HIV-infected individuals in the United States and other countries in which HIV-positive persons have access to effective combination antiretroviral therapy (cART). Our prior work showed that pretreatment/postdiagnosis plasma levels of some cytokines, such as IL6, IL10, and CXCL13, have the potential to serve as indicators of clinical response to treatment and survival in ARL. The aims of this study were to identify novel prognostic biomarkers for response to treatment and/or survival in persons with ARL, including biomarkers of microbial translocation and inflammation. We quantified plasma levels of several biomarkers (sCD14, LBP, FABP2, EndoCab IgM, IL18, CCL2/MCP-1, sCD163, IP-10/CXCL10, TARC/CCL17, TNFα, BAFF/BLyS, sTNFRII, sCD44, and sIL2Rα/sCD25) by multiplexed immunometric assays (Luminex) or ELISA in plasma specimens obtained from ARL patients enrolled in the AMC-034 trial, which compared infusional combination chemotherapy (EPOCH: etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) with concurrent or sequential rituximab. Plasma was collected prior to the initiation of therapy (n = 57) and after treatment initiation (n = 55). We found that several biomarkers decreased significantly after treatment, including TNFα, sCD25, LBP, and TARC (CCL17). Moreover, pretreatment plasma levels of BAFF, sCD14, sTNFRII, and CCL2/MCP-1 were univariately associated with overall survival, and pretreatment levels of BAFF, sTNFRII, and CCL2/MCP-1 were also associated with progression-free survival. Our results suggest that patients with ARL who responded to therapy had lower pretreatment levels of inflammation and microbial translocation as compared with those who did not respond optimally.

Head and neck squamous cell carcinoma in people living with HIV in France

ObjectivesHead and neck squamous cell carcinoma (HNSCC), mainly due to smoking, is one of the leading causes of cancer deaths. However, an increasing number of tumors – especially oropharyngeal cancer – are reported in non-smokers in association with the human papillomavirus (HPV). As HIV-infected individuals are particularly at risk of HPV-related disease, we aimed to describe the burden of HNSCC in this population. MethodsRetrospective chart review of patients from HIV clinics diagnosed with HNSCC between 2004 and 2014. Case patients were defined using the International Classification of Disease for Oncology (3rd edition). Age at HIV diagnosis and time from HIV diagnosis to HNSCC diagnosis were collected. Oropharyngeal cancers were considered as potentially HPV-related cancers, and their prevalence was compared with other HNSCCs over time. ResultsThe 286 patients enrolled in the study had a median age at HNSCC diagnosis of 52 years; 84% were males and 68% had a history of smoking. The oropharynx was the most frequent site (41%), followed by cancer of the oral cavity (31%), larynx (22%), and hypopharynx (7%). The prevalence (and proportion) of potentially HPV-related cancers increased significantly over time with a mean of 0.78 additional case patient per year. ConclusionThe prevalence of HNSCC is modest compared with other cancers in HIV-infected individuals. The prevalence of oropharynx carcinoma, a potentially HPV-related carcinoma, seems to increase over time. Even if tobacco may be an important contributor, the role of HPV in HIV-infected individuals presenting with HNSCC should be investigated.

2 - Preliminary validation of a health-related quality of life symptom index for persons treated or actively monitored for anal HSIL (AMC –A02, -A03)

Precancerous anal high-grade squamous intraepithelial lesions (HSIL) and its associated treatments have the potential to reduce health-related quality of life (HRQoL) in impacted individuals. The ANCHOR (ANal Cancer HSIL Outcomes Research) trial aims to determine whether treating anal HSIL, versus active monitoring, is effective in reducing incidence of anal cancer in HIV-infected individuals. The present study sought to establish preliminary psychometric evidence of the 25-item ANCHOR Health-Related Symptom Inventory (A-HRSI). Eligible ANCHOR participants recruited within two-weeks post-treatment or randomization to active surveillance completed the A-HRSI and well-established legacy HRQoL measures (i.e., Functional Assessment of Cancer Therapy – General [FACT-G] and MD Anderson Symptom Inventory [MDASI]) via telephone. Construct validity was assessed using an exploratory factor analysis (EFA). Pearson correlations were then calculated between summed items within the resulting A-HRSI latent factors and legacy measure outcome subscales to establish convergent and divergent validity. 200 participants were enrolled. EFA provided initial confirmation that the A-HRSI items are best represented by the proposed broad three-factor structure (e.g., physical symptoms, physical impacts, psychological symptoms). These three factors had fair to moderate Pearson correlations with FACT-G Total and MDASI Symptom Severity and Interference subscales. Preliminary psychometric evidence exists to support the construct validity of the A-HRSI, indicating this measure can capture disease- and treatment-related physical and psychological symptoms and physical impacts. Clinical responsiveness and Spanish-translation of this measure will be completed prior to ultimately deploying this measure in the ANCHOR trial to facilitate participant reporting of their HRQoL to inform clinical decision-making.

Role of Pattern Recognition Receptors in KSHV Infection.

Kaposi’s sarcoma-associated herpesvirus or Human herpesvirus-8 (KSHV/HHV-8), an oncogenic human herpesvirus and the leading cause of cancer in HIV-infected individuals, is a major public health concern with recurring reports of epidemics on a global level. The early detection of KSHV virus and subsequent activation of the antiviral immune response by the host’s immune system are crucial to prevent KSHV infection. The host’s immune system is an evolutionary conserved system that provides the most important line of defense against invading microbial pathogens, including viruses. Viruses are initially detected by the cells of the host innate immune system, which evoke concerted antiviral responses via the secretion of interferons (IFNs) and inflammatory cytokines/chemokines for elimination of the invaders. Type I IFN and cytokine gene expression are regulated by multiple intracellular signaling pathways that are activated by germline-encoded host sensors, i.e., pattern recognition receptors (PRRs) that recognize a conserved set of ligands, known as ‘pathogen-associated molecular patterns (PAMPs)’. On the contrary, persistent and dysregulated signaling of PRRs promotes numerous tumor-causing inflammatory events in various human cancers. Being an integral component of the mammalian innate immune response and due to their constitutive activation in tumor cells, targeting PRRs appears to be an effective strategy for tumor prevention and/or treatment. Cellular PRRs are known to respond to KSHV infection, and KSHV has been shown to be armed with an array of strategies to selectively inhibit cellular PRR-based immune sensing to its benefit. In particular, KSHV has acquired specific immunomodulatory genes to effectively subvert PRR responses during the early stages of primary infection, lytic reactivation and latency, for a successful establishment of a life-long persistent infection. The current review aims to comprehensively summarize the latest advances in our knowledge of role of PRRs in KSHV infections.

KSHV oral shedding and plasma viremia result in significant changes in the extracellular tumorigenic miRNA expression profile in individuals infected with the malaria parasite.

Kaposi's sarcoma herpesvirus (KSHV) is the etiological agent of Kaposi’s sarcoma (KS). Both KSHV and HIV infections are endemic in Uganda, where KS is among the most common cancers in HIV-infected individuals. Recent studies examined the use of small RNAs as biomarkers of disease, including microRNAs (miRNAs), with viral and tumor-derived miRNAs being detected in exosomes from individuals with KSHV-associated malignancies. In the current study, the host and viral extracellular mature miRNA expression profiles were analyzed in blood of KS-negative individuals in Uganda, comparing those with or without KSHV detectable from the oropharynx. We observed increased levels of cellular oncogenic miRNAs and decreased levels of tumor-suppressor miRNAs in plasma of infected individuals exhibiting oral KSHV shedding. These changes in host oncomiRs were exacerbated in people co-infected with HIV, and partially reversed after 2 years of anti-retroviral therapy. We also detected KSHV miRNAs in plasma of KSHV infected individuals and determined that their expression levels correlated with KSHV plasma viremia. Deep sequencing revealed an expected profile of small cellular RNAs in plasma, with miRNAs constituting the major RNA biotype. In contrast, the composition of small RNAs in exosomes was highly atypical with high levels of YRNA and low levels of miRNAs. Mass spectrometry analysis of the exosomes revealed eleven different peptides derived from the malaria parasite, Plasmodium falciparum, and small RNA sequencing confirmed widespread plasmodium co-infections in the Ugandan cohorts. Proteome analysis indicated an exosomal protein profile consistent with erythrocyte and keratinocyte origins for the plasma exosomes. A strong correlation was observed between the abundance of Plasmodium proteins and cellular markers of malaria. As Plasmodium falciparum is an endemic pathogen in Uganda, our study shows that co-infection with other pathogens, such as KSHV, can severely impact the small RNA repertoire, complicating the use of exosome miRNAs as biomarkers of disease.

The world-wide incidence of Kaposi's sarcoma in the HIV/AIDS era.

Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunosuppression or immunodeficiency. Consequently, KS is one of the most common cancers in HIV-infected individuals and frequently occurs among transplant recipients. Nevertheless, its incidence in different populations is not well understood. We searched online databases for publications on KS incidence. A random-effect meta-analysis was performed to combine the KS incidences and incidence rate ratios (IRRs) for associated risk factors. Seventy-six eligible studies representing 71 time periods were included. For HIV-infected people, the overall KS incidence was 481.54 per 100000 person-years with a 95% confidential interval (CI) of 342.36-677.32 per 100000 person-years. HIV-infected men who have sex with men (MSM) had the highest incidence of KS (1397.11 per 100000 person-years; 95% CI 870.55-2242.18 per 100000 person-years). The incidence of KS was significantly lower in female than in male individuals (IRR 3.09; 95% CI 1.70-5.62). People receiving highly active antiretroviral therapy (HAART) had a lower incidence compared with people who had never received HAART (IRR 6.57; 95% CI 1.91-24.69). The incidence of KS was 68.59 (95% CI 31.39-149.86) per 100000 person-years in transplant recipients, 52.94 (95% CI 39.90-70.20) per 100000 person-years in children with HIV infection, and 1.53 (95% CI 0.33-7.08) per 100000 person-years in the general population. Globally, a relatively high incidence of KS was found among HIV-seropositive people and, in particular, in HIV-infected MSM. The introduction of HAART has largely prevented the development of KS, but it has not entirely removed the challenge of KS. In Africa, in particular, KS imposes a very heavy disease burden, which can mainly be attributed to the high prevalence of KS-associated herpesvirus and poor access to HAART.

HIV, HPV, and microbiota

Altered interplay between gut mucosa and dysbiotic bacteria during HIV infection seems to fuel chronic immune dysfunction and might explain the excess rates of human papillomavirus (HPV)-associated anal cancer in HIV-infected individuals. Here, we show in HIV-infected MSM undergoing screening for HPV-related cancer that specific fecal and mucosal bacteria are able to predict the existence of precancerous anal lesions. If confirmed, these bacterial biomarkers could be exploited either as diagnostic tools or therapeutic targets.

Human papillomavirus-associated anal and cervical cancers in HIV-infected individuals: incidence and prevention in the antiretroviral therapy era.

The incidence of human papillomavirus (HPV)-related cancers has increased (anal cancer) or not declined (cervical cancer) since the introduction of antiretroviral therapy (ART). This article reviews recent data on incidence and prevention efforts for HPV-related cancers in the ART era. ART may confer some benefit with respect to reducing the risk of anal high-grade squamous intraepithelial lesion and cancer, but the degree of that benefit appears to be limited. The prevalence of anal HPV infection, anal high-grade squamous intraepithelial lesion, and anal cancer remain high among individuals on effective ART. The incidence of cervical cancer is high among HIV-infected women, particularly in countries wherein there are no organized cervical cancer prevention programmes. Efforts are in progress to define optimal screen-and-treat cervical cancer prevention programmes in different clinical settings and to define the efficacy of secondary prevention programmes for prevention of anal cancer. HPV-related cancers are likely to remain an important problem in HIV-infected men and women for the foreseeable future, even among those on effective ART.

Recent advances in understanding Kaposi's sarcoma-associated herpesvirus.

Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is an oncogenic human herpesvirus. KSHV is associated with three cancers in the human population: KS, primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD). KS is the leading cause of cancer in HIV-infected individuals. In this review, we discuss the most recent discoveries behind the mechanisms of KSHV latency maintenance and lytic replication. We also review current therapies for KSHV-associated cancers.

Genital Epstein Barr Virus is associated with higher prevalence and persistence of anal human papillomavirus in HIV-infected men on antiretroviral therapy.

BackgroundEpstein Barr virus (EBV) and human papillomavirus (HPV) can co-exist in pharyngeal and cervical malignancies. However, the natural history and factors associated with persistent HPV infection among HIV-infected men who have sex with men (MSM) are unclear.Methods131 HIV-infected MSM were followed for 48 weeks and screened for multiple co-infections, including seminal EBV DNA and high risk (HR)-HPV messenger RNA (mRNA) at several sites (semen, anal, pharynx). Primary analysis tested if seminal EBV shedding was associated with increased prevalence of HR-HPV at baseline using univariate tests and multivariable logistic regression. In participants with detectable anal HR-HPV at baseline, we tested if presence of seminal EBV shedding at baseline was also predictive of reduced HR-HPV clearance by log-rank test (over 48 weeks of follow-up).ResultsBaseline prevalence of HR-HPV was: anal 44 % (N = 54/121); pharynx 3.8 % (N = 5/131); semen 7.1 % (N = 7/98). Seminal EBV shedding was present in 28 % of participants and was associated with more than double the prevalence of detectable anal HR-HPV mRNA (71.4 % for EBV shedders versus 33.3 % for non-shedders, p < 0.01). In participants with detectable anal HR-HPV at baseline, we found increased persistence of HR-HPV over 48 weeks of follow-up (measured as time to first negative HR-HPV test in the EBV shedding group (p < 0.01).ConclusionsSeminal EBV shedding was associated with an increased risk of having detectable anal HR-HPV in a cohort of HIV-infected MSM on suppressive ART. Future studies should examine if co-infection with EBV and HR-HPV may act synergistically in pathogenesis of anal cancer in HIV-infected individuals.

Patterns of HIV viremia and viral suppression before diagnosis of non-AIDS-defining cancers in HIV-infected individuals.

BackgroundThe association between HIV viremia and non-AIDS-defining cancers (NADCs) is not well characterized. Viremia may contribute directly or indirectly to cancer development and may have a differential impact on various cancer types. Our objective was to characterize patterns of HIV viremia in a retrospective, urban, clinical cohort (N = 320) of patients diagnosed with NADCs.FindingsThe most common NADC’s were lung (n = 60), prostate (n = 47), oropharyngeal (n = 32), liver (n = 29), and anal cancer (n = 20) and Hodgkin lymphoma (n = 18). In the year before cancer diagnosis, 66 % of all patients were virally suppressed. Patients with oropharyngeal (70 %) and prostate cancer (78 %) had a higher proportion of visits with suppressed viral loads. Patients diagnosed with anal cancer and Hodgkin lymphoma were infrequently virally suppressed and more frequently had viral loads ≥5 log10 copies/ml in the ten years prior to cancer diagnosis.ConclusionsIn this cohort of HIV-infected patients diagnosed with NADCs, there were important differences in the patterns and levels of viremia between the different NADCs in the ten years prior to cancer diagnosis. Patients with anal cancer and Hodgkin lymphoma had the highest proportion of high level viremia in the ten years before cancer and the lowest frequency of viral load suppression at cancer diagnosis.

Association Between Educational Level and Risk of Cancer in HIV-infected Individuals and the Background Population: Population-based Cohort Study 1995-2011.

Human immunodeficiency virus (HIV)-infected individuals have increased risk of cancer. To our knowledge, no previous study has examined the impact of socioeconomic position on risk and prognosis of cancer in HIV infection. Population-based cohort-study, including HIV-infected individuals diagnosed (without intravenous drug abuse or hepatitis C infection) (n = 3205), and a background population cohort matched by age, gender, and country of birth (n = 22 435) were analyzed. Educational level (low or high) and cancer events were identified in Danish national registers. Cumulative incidences, incidence rate ratios (IRRs), and survival using Kaplan-Meier methods were estimated. Low educational level was associated with increased risk of cancer among HIV-infected individuals compared to population controls: all (adjusted-IRRs: 1.4 [95% confidence interval {CI}, 1.1-1.7] vs 1.1 [95% CI, .9-1.2]), tobacco- and alcohol-related (2.1 [95% CI, 1.3-3.4] vs 1.3 [95% CI, 1.1-1.6]), and other (1.7 [95% CI, 1.1-2.8] vs 0.9 [95% CI, .7-1.0]). Educational level was not associated with infection-related or ill-defined cancers. One-year-survival was not associated with educational level, but HIV-infected individuals with low educational level had lower 5-year-survival following infection-related and ill-defined cancers. Education is associated with risk and prognosis of some cancers in HIV infection, and diverges from what is observed in the background population.

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.

HPV and anal cancer in HIV-infected individuals: a review.

HIV infection is one of the strongest risk factors for anal squamous cell cancer (ASCC). Most ASCC are caused by HPV, and most HPV-associated ASCC are caused by HPV-16. Anal HPV infections are very common in men who have sex with men (MSM), and nearly universal among HIV-infected MSM. High-grade anal intraepithelial neoplasia (HGAIN), the precursor for ASCC, is present in about 30 % of HIV+ MSM, but neither the progression rate to ASCC nor the regression rate are known. The incidence rate of ASCC among HIV-infected people has risen in the first decade after cART became available, but appears to be plateauing recently. Anal cytology has poor sensitivity and specificity. High resolution anoscopy (HRA) is advocated by some as a screening tool in high-risk groups, but is cumbersome and time-consuming and it is unknown whether HRA followed by treatment of HGAIN prevents ASCC. More research is needed on progression and regression rates of HGAIN, on effective therapy of HGAIN, and on biomarkers that predict HGAIN or anal cancer. HPV vaccination and earlier start of cART may prevent most anal cancers in the long run.

Cancer Trends in HIV-Infected People During the Era of Effective Antiretroviral Therapy

Cancer trends in HIV-infected people may be influenced by changes in group demographics (e.g., aging), in background rates of cancer in the general population, and in the relative risk for cancer in HIV-infected individuals compared with the general population. Now, investigators have used data from the HIV/AIDS Cancer Match Study, which links HIV and cancer registries in seven states, to examine how these factors have influenced time trends for 10 cancers in HIV-infected patients. Data were evaluated …

Screening guidelines for non-AIDS defining cancers in HIV-infected individuals.

The growing burden of non-AIDS defining malignancies (non-ADMs) among people living with HIV/AIDS (PLWHA) highlights the need for cancer prevention and early detection. In this article, we propose screening guidelines for non-ADMs in PLWHA. A number of recent findings may help direct cancer screening guidelines in PLWHA. Screening for lung cancer with low-dose helical chest computerized tomography (LDCT) in the National Lung Screening Trial data demonstrated a decrease in lung cancer and all-cause mortality. Recent studies have demonstrated a favorable experience among PLWHA with liver transplantation. Overdiagnosis is common with breast and prostate cancer screening. Anal cancer rates were substantially higher for HIV-infected MSM, other men and women than for HIV-uninfected individuals. Screening recommendations for the general population can be applied to PLWHA patients for breast, colon and prostate cancer. Screening for lung cancer with LDCT could be considered in PLWHA at risk. American Association for the Study of Liver Diseases screening recommendations with biennial ultrasonography may be applied to at-risk PLWHA for hepatocellular carcinoma. All HIV-infected adults should be offered anal cancer screening as part of clinical care at specialized centres.

Oral human papillomavirus infection and head and neck cancers in HIV-infected individuals.

HIV-infected individuals are living longer due to effective antiretroviral therapy and may therefore have a greater opportunity to develop human papillomavirus (HPV)-associated malignancies. This review describes the risk factors and burden of oral HPV infection and HPV-associated head and neck cancer (HNC) among HIV-infected individuals. Oral HPV infection is commonly detected in HIV-infected individuals and is elevated among those with a higher number of lifetime oral sexual partners, current tobacco use and immunosuppression. There are limited data on the natural history of oral HPV, but initial studies suggest that the majority of infections clear within 2 years. Although HIV-infected individuals are at a much higher risk of most HPV-associated cancers than the general population, studies suggest HIV-infected individuals have a more modest 1.5-4-fold greater risk for HPV-associated HNC. HIV-infected individuals are living longer, have a high prevalence of oral HPV infection and have many of the currently determined risk factors for HPV-associated HNC.

Pathology of lymphoma in HIV

HIV-infected individuals have a greatly increased risk of developing malignancies, even when HIV infection is successfully controlled with antiretrovirals. Non-Hodgkin's lymphoma is considered an AIDS-defining entity, and this disease is currently the most common type of cancer in HIV-infected individuals in the USA and Europe. Here, we describe the different types of lymphomas occurring in individuals with AIDS, and the most relevant pathologic features helpful for histologic and immunohistochemical diagnosis. The incidence of some AIDS-related lymphoma subtypes has changed since the introduction of combined antiretroviral therapy, and some of the diagnostic methodologies have evolved. New biomarkers of disease have been identified, which may be useful for diagnosis. Better pathological classification strategies and deeper molecular understanding of the different lymphoma subtypes that occur in people with AIDS will begin to allow the transition to more precise diagnosis and targeted treatments.

Incidence and timing of cancer in HIV-infected individuals following initiation of combination antiretroviral therapy.

Cancer is an important cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), but patterns of cancer incidence after combination antiretroviral therapy (ART) initiation remain poorly characterized. We evaluated the incidence and timing of cancer diagnoses among patients initiating ART between 1996 and 2011 in a collaboration of 8 US clinical HIV cohorts. Poisson regression was used to estimate incidence rates. Cox regression was used to identify demographic and clinical characteristics associated with cancer incidence after ART initiation. At initiation of first combination ART among 11 485 patients, median year was 2004 (interquartile range [IQR], 2000-2007) and median CD4 count was 202 cells/mm(3) (IQR, 61-338). Incidence rates for Kaposi sarcoma (KS) and lymphomas were highest in the first 6 months after ART initiation (P < .001) and plateaued thereafter, while incidence rates for all other cancers combined increased from 416 to 615 cases per 100 000 person-years from 1 to 10 years after ART initiation (average 7% increase per year; 95% confidence interval, 2%-13%). Lower CD4 count at ART initiation was associated with greater risk of KS, lymphoma, and human papillomavirus-related cancer. Calendar year of ART initiation was not associated with cancer incidence. KS and lymphoma rates were highest immediately following ART initiation, particularly among patients with low CD4 cell counts, whereas other cancers increased with time on ART, likely reflecting increased cancer risk with aging. Our results underscore recommendations for earlier HIV diagnosis followed by prompt ART initiation along with ongoing aggressive cancer screening and prevention efforts throughout the course of HIV care.

Natural History of Anal vs Oral HPV Infection in HIV-Infected Men and Women

Human immunodeficiency virus (HIV)-infected individuals are at greater risk for human papillomavirus (HPV)-associated anal than oropharyngeal cancers. The prevalence of anal vs oral HPV infections is higher in this population, but whether this is explained by higher incidence or persistence is unknown. Oral rinse and anal swab samples were collected semiannually from 404 HIV-infected adults in Baltimore, Maryland. Samples were tested for 37 HPV types using PGMY09/11 primers and reverse line-blot hybridization. Risk factors for HPV persistence were explored using adjusted Wei-Lin-Weissfeld models. The prevalence (84% vs 28%), incidence (145 vs 31 per 1000 person-months), and 12-month persistence (54% vs 29%) were higher for anal vs oral HPV infections, respectively (each P < .001). Heterosexual men had lower incidence of anal HPV than men who have sex with men and women, but a higher incidence of oral HPV infection (test of interaction P < 0.001). In adjusted analyses, risk factors for HPV persistence included prevalent vs incident (adjusted hazard ratio [aHR] = 4.0; 95% confidence interval [CI], 3.5-4.8) and anal vs oral HPV infections (aHR = 1.5; 95% CI, 1.2-1.9). The higher incidence and persistence of anal vs oral HPV infections likely contributes to the higher burden of anal as compared to oral HPV-associated cancers in HIV-infected individuals.