Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients.

PURPOSE: To determine incidence of non-AIDS-defining cancers (NADC) in HIV-infected patients before (P1) and during (P2) the use of highly active antiretroviral therapy (HAART) relative to that observed in the French general population (FGP) of the same age and sex. PATIENTS AND METHODS: Sex- and age-adjusted NADC standardized incidence ratios (SIR), with FGP as reference, were estimated in 1992 to 1995 (P1) and in 1996 to 1999 (P2) in a French Hospital Database on HIV prospective hospital cohort study. RESULTS: NADCs were diagnosed in 260 patients during P1 and 391 patients during P2 among the 77,025 patients included in the database between January 1, 1992, and December 31, 1999. Estimated incidence of all cancers was higher in HIV-infected men than in FGP during both periods (P1 SIR = 2.36 and P2 SIR = 1.91). No excess of cancers was observed among HIV-infected women in either period. Incidence of all cancers did not change from P1 to P2 in either sex (SIR = 0.96 for men and 1.00 for women). In contrast, incidence of Hodgkin's disease (HD) was higher than in FGP in both sexes and both periods and increased in P2 as compared with P1; incidence of lung cancer was higher in both sexes during P2. CONCLUSION: Relative to FGP, the overall incidence of NADCs was increased in HIV-infected men but not in women and did not differ between P1 and P2. Only HD was much more common in HIV infection, and the potential role of HAART on HD cannot be excluded.     

Increased risk of histologically defined cancer subtypes in human immunodeficiency virus-infected individuals: Clues for possible immunosuppression-related or infectious etiology

BACKGROUND:

Malignancies that occur in excess among human immunodeficiency virus (HIV)‐infected individuals may be caused by immunosuppression or infections. Because histologically defined cancer subtypes have not been systematically evaluated, their risk was assessed among people with acquired immunodeficiency syndrome (AIDS).

METHODS:

Analyses included 569,268 people with AIDS from the HIV/AIDS Cancer Match Study, a linkage of 15 US population‐based HIV/AIDS and cancer registries during 1980 to 2007. Standardized incidence ratios (SIRs) were estimated to compare cancer risk in people with AIDS to the general population overall, and stratified by age, calendar period (a proxy of changing HIV therapies), and time since onset of AIDS (a proxy of immunosuppression).

RESULTS:

Sixteen individual cancer histologies or histology groupings manifested significantly elevated SIRs. Risks were most elevated for adult T cell leukemia/lymphoma (SIR = 11.3), neoplasms of histiocytes and accessory lymphoid cells (SIR = 10.7), giant cell carcinoma (SIR = 7.51), and leukemia not otherwise specified (SIR = 6.69). SIRs ranged from 1.4 to 4.6 for spindle cell carcinoma, bronchioloalveolar adenocarcinoma, adnexal and skin appendage neoplasms, sarcoma not otherwise specified, spindle cell sarcoma, leiomyosarcoma, mesothelioma, germ cell tumors, plasma cell tumors, immunoproliferative diseases, acute lymphocytic leukemia, and myeloid leukemias. For several of these cancer subtypes, significant declines in SIRs were observed across calendar periods (consistent with decreasing risk with improved HIV therapies) or increase in SIRs with time since onset of AIDS (ie, prolonged immunosuppression).

CONCLUSIONS:

The elevated risk of certain cancer subtypes in people with AIDS may point to an etiologic role of immunosuppression or infection. Future studies are needed to further investigate these associations and evaluate candidate infectious agents. Cancer 2012. © 2012 American Cancer Society.     

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

Background

The 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.

Findings

The 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.

Conclusions

In 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.

     

Human papillomavirus-associated anogenital neoplasia and other solid tumors in human immunodeficiency virus-infected individuals.

The incidence and variety of solid tumors reported among human immunodeficiency virus (HIV)-infected individuals are increasing. Among the most common of these tumors are anogenital malignant and premalignant tumors associated with human papillomavirus infection. Cervical intraepithelial neoplasia is one such human papillomavirus-associated lesion and appears to be more common among women with HIV infection than HIV-negative women. Cervical intraepithelial neoplasia also appears to progress more rapidly among HIV-positive women, and these women are at high risk for progression to invasive cervical cancer in the absence of rigorous screening, treatment, and follow-up. Likewise, HIV-positive men with a history of receptive anal intercourse have a high prevalence of anal intraepithelial neoplasia and a rapidly increasing incidence of invasive anal cancer. The approach to the prevention of anal cancer is similar to that of cervical cancer, although experience with diagnostic and treatment measures is still limited for anal disease. As individuals with advanced immunosuppression live longer due to improvements in the medical therapy for HIV infection, it is expected that the incidence of human papillomavirus-associated neoplasia, as well as that of other tumors, will continue to increase.     

The risk of hepatocellular carcinoma among individuals with acquired immunodeficiency syndrome in the United States

BACKGROUND:

Hepatocellular carcinoma (HCC) is a concern among individuals with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS).

METHODS:

The authors analyzed population‐based registry linkage data from the US HIV/AIDS Cancer Match Study (1980‐2009) to examine the risk and trends of HCC among individuals with AIDS. Standardized incidence ratios (SIRs) were used to measure HCC risk relative to the general population, and Poisson regression was used to calculate incidence rate ratios (RR) comparing incidence among individuals with AIDS. People with AIDS were categorized according to their HIV risk group into high and low hepatitis C virus (HCV) prevalence groups based on their HIV transmission risk category.

RESULTS:

Among 615,150 individuals with AIDS, HCC risk was elevated almost 4 times compared with the risk in the general population (N = 366; SIR, 3.8; 95% confidence interval, 3.5‐4.3). Although HCC incidence increased steadily across calendar periods (P_trend < .0001; adjusted for sex and age), the excess risk in individuals with AIDS compared with the general population remained somewhat constant (SIRs range, 3.5‐3.9) between the monotherapy/dual therapy era (1990‐1995) and the recent highly active antiretroviral therapy era (2001‐2009). In a multivariate model adjusting for sex, race/ethnicity, and attained calendar period, HCC incidence increased with advancing age (P_trend < .0001) and was associated with HIV risk groups with a known higher prevalence of HCV (adjusted RR, 2.2; 95% confidence interval, 1.8‐2.8).

CONCLUSIONS:

HCC incidence in individuals with AIDS has increased over time despite improved HIV treatment regimens, likely reflecting prolonged survival with chronic liver disease. The high incidence in older adults suggests that this cancer will increase in importance with aging of the HIV‐infected population. Cancer 2012. Published 2012 by the American Cancer Society.     

AIDS-defining and non-AIDS-defining malignancies: cancer occurrence in the antiretroviral therapy era

PURPOSE OF REVIEW: Effective antiretroviral therapy use has resulted in a large number of older individuals living with HIV. Recent literature is reviewed with respect to the incidence and risk factors for cancer in HIV patients. RECENT FINDINGS: Previous studies have demonstrated substantial declines in AIDS-defining malignancies in the era of antiretroviral therapy, with clear links to better immune function. Increases in non-AIDS-defining malignancies such as Hodgkin's disease, skin, lung, anal, and kidney cancers have been noted by some but not all authors. Certain non-AIDS-defining malignancies may be related to immunodeficiency, although data are conflicting. Recent studies have indicated that confounding by traditional risk factors, including cigarette use, may account for some of the increased risk of lung and other cancers in HIV patients. SUMMARY: Non-AIDS-defining malignancies account for more morbidity and mortality than AIDS-defining malignancies in the antiretroviral therapy era. Traditional risk factors play a significant role in the increased risk of non-AIDS-defining malignancies for HIV-infected individuals, but do not entirely explain the excess cancer risk. Unanswered questions remain including the relationship of immunodeficiency and the risk of site-specific non-AIDS-defining malignancies, and the effect of antiretroviral therapy duration and drug class on cancer risk.     

Invasive and preinvasive cervical neoplasia in human immunodeficiency virus-infected women

An association between human immunodeficiency virus (HIV) infection and cervical neoplasia in women has recently been recognized. Cervical cancer was designated as a diagnostic criteria for acquired immunodeficiency syndrome (AIDS) in HIV-infected women in 1993. The two conditions share a number of risk factors, including a history of multiple sexual partners and disproportionate effect on younger women and ethnic minorities. HIV appears to accelerate the pathogenesis of cervical neoplasia at the molecular level, although clinical evidence of disease progression is limited. The optimal strategy for screening HIV-infected women for cervical neoplasia is unclear, but should include at least an annual Papanicolaou (Pap) smear. Preinvasive cervical neoplasia in HIV-infected women should be treated with standard excisional/ ablative therapy, followed by vaginal 5-flourouracil cream. Invasive cervical cancer should be treated with standard surgical therapy or radiotherapy. Recurrence rates are high following treatment of either invasive or preinvasive disease, but are reduced in women undergoing highly active antiretroviral therapy.     

The prevalence of human papillomavirus genotypes in nonmelanoma skin cancers of nonimmunosuppressed individuals identifies high-risk genital types as possible risk factors

Nonmelanoma skin cancer is the most commonly diagnosed malignant disease in Caucasians. Known risk factors include fair skin, sun exposure, male gender, advancing age, and the presence of solar keratosis. No viral risk factors have been established thus far. To examine the association between nonmelanoma skin cancer and infection with human papilloma virus (HPV) types, we performed a retrospective study in which skin biopsies were collected from 496 nonimmunosuppressed patients attending dermatologic clinics during a defined period and for whom a biopsy or resection of a tumor was indicated for medical reasons. A total of 390 patients with histologically confirmed diagnosis of warts (n = 209), solar keratosis or Bowen's disease (n = 91), squamous cell carcinoma (n = 72), or basal cell carcinoma (n = 18), as well as 106 control patients with normal skin was analyzed for infection with HPV and, if positive, HPV typed by sequencing. Logistic regression was performed to separately investigate association of certain HPV types with the occurrence of warts, precancerous lesions, and skin cancer compared with normal skin. For all three histological groups, both crude risk and risk adjusted for age, sex, and sun exposure were calculated. HPV DNA was detected in only 4.7% of controls, in 90.9% of benign warts, in 60.4% of precancerous lesions, in 59.7% of squamous cell carcinoma, and in 27.8% of basal cell carcinoma, which demonstrates that viral infection is specifically linked to skin disorders. The distribution of viral types found is distinctly different between warts and precancers or cancers, supporting an etiologic role of specific HPV types. This is supported by statistical analysis, where after adjusting for age, gender, and sun exposure, the odds ratio for nonmelanoma skin cancer in patients who were DNA positive for the high-risk mucosal HPV types, 16, 31, 35, and 51 was 59 (95% confidence interval, 5.4-645) with normal skin as controls. These findings suggest that persistent infections of the skin with high risk genital HPV types recently identified as significant risk factors for cervical cancer may also represent a risk factor for nonmelanoma skin cancer in a nonimmunosuppressed population.     

Dietary risk factors for upper aerodigestive tract cancers

We examined the association between whole-grain intake and incident upper aerodigestive tract cancer in a cohort of 34,651 postmenopausal, initially cancer-free women. We also studied established risk factors for upper aerodigestive cancers, including fruit and vegetable intake, smoking and alcohol intake. A mailed questionnaire at baseline in 1986 included a food-frequency questionnaire and assessment of other cancer risk factors. During the 14-year follow-up period, 169 women developed cancer of the upper aerodigestive tract. For all upper aerodigestive cancers together, significant inverse associations were observed for the highest compared to the lowest tertile of whole grains [relative risk (RR) = 0.53, 95% confidence interval (CI) 0.34-0.81] and yellow/orange vegetables (RR = 0.58, 95% CI 0.39-0.87). In addition, those in the highest compared to lowest tertile of fiber intake from whole grain were less likely to develop upper aerodigestive tract cancer (RR = 0.56, 95% CI 0.37-0.84); fiber intake from refined grain was not significantly associated with upper aerodigestive tract cancer. Findings were generally similar for oropharyngeal (n = 53), laryngeal (n = 21), nasopharyngeal/salivary (n = 18), esophageal (n = 21) and gastric (n = 56) cancers, though numbers of cases were too small for statistical testing within individual cancers. These findings confirm previous observations that high intake of fruits and vegetables and that intake of whole grains and the fiber derived from them may reduce risk of upper aerodigestive tract cancers.     

Increased risk factors for the occurrence of bladder cancer]

Risk factors of bladder cancer development were studied in a population-based case-control epidemiological study performed in Moscow. Relative risk (RR) indexes appeared to be increased in smokers (4.2) and ex-smokers (3.5) with statistically significant trends for two most important factors such as duration of smoking and duration of withdrawal. A pronounced although insignificant increase in the RR indexes was established for drivers (3.0) and a slight insignificant rise-for gas arc welding operators (1.5). The indexes were increased in subjects with a family history of cancer. The relative risk of cancer was significantly lower in beta-carotene consumers. A preventive effect of polyunsaturated fatty acids and oil and margarine used for frying was established. Risk of bladder cancer tended to increase with a rise in dietary protein. A dose-effect type inhibition of advancement of the disease by vitamin C was observed.     

Comparative case-referent study of risk factors among hormone-related female cancers in Japan.

To assess the impact of reproductive and anthropometric factors as a risk indicator for female cancers in hormone-related organs, i.e., the breast, endometrium and ovary, we conducted a comparative case-referent study using data from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center (HERPACC), Japan. The case group consisted of 1,465, 133 and 99 women who had first been diagnosed as having breast, endometrial and ovarian cancer, respectively. The referents were 25,488 female first-visit outpatients who had not previously been diagnosed with any type of cancer. The odds ratios (ORs) and their 95% confidence intervals (95%CI) were estimated using an unconditional logistic regression model. An inverse association with experience of delivery and a positive association with body mass index (BMI) and with change of BMI after 20 years of age, were observed consistently for all three cancer sites. We observed similar risk and protective factors for breast and endometrial cancer, but the effect of reproduction and overweight condition (BMI> or =25) were more prominent in endometrial cancer. Although the present study failed to find site-specific risk factors for ovarian cancer, the results provided evidence that being overweight and/or weight gain in adult life is a common risk factor for all three cancer sites. The results obtained from this study suggested that avoidance of weight gain may reduce the risk of female hormone-related cancers.     

Characteristics of colorectal cancer in the human immunodeficiency virus-infected African American population

Colorectal Cancer (CRC) is the second leading cause of cancer mortality in the United States. African Americans (AAs) have the highest incidence of CRC of any American ethnic group. Survival from CRC in AAs is lower than in Caucasians, and the mean age of CRC development in AAs is younger. The AA community also has a high rate of HIV infection, accounting for 50.3% of all cases despite making up only 13.6% of the population. This retrospective cohort study identified 17 AA HIV patients with CRC. The patients were matched with 42 HIV-negative CRC patients (controls), based on age, sex, and TNM stage. Data were obtained from 3 hospitals in New Jersey: St. Michael's Medical Center, Trinitas Medical Center and St. Joseph's Medical Center. The age, sex, HIV status, tumor site, stage, drug usage, Hepatitis C status, and survival outcome of subjects and controls were compared. Data from the Surveillance Epidemiology & End Results (SEER) specific to AAs were also compared. The mean age of CRC diagnosis was younger, 50.7 years (median: 52 years, range: 35-71 years), versus 59.42 years (median: 66 years) (P < 0.0001) in the SEER AA population. Of the patients, 29.4% were diagnosed with CRC at less than 45 years of age, versus only 6.35% of the SEER AA population (P < 0.0002). The male-to-female ratio was 11:6. Seven individuals used IV drugs, and 7 had hepatitis C. The mean CD4+ T-cell count was 510.81 cells/mm(3) (median 419). At the time of CRC diagnosis, the average duration of HIV infection was 7.6 years (range 0-22.4 years).Of patients, 87.5% had left-sided CRC, versus 57.55% of the SEER population (P < 0.024). Of the patients, 52.94% had stage III-IV, at diagnosis, versus 43.84% in SEER. There was no statistically significant survival difference between the cases and controls. In our cohort of HIV-infected AA's with CRC, the staging and outcome of CRC did not appear to be affected by the degree of immunosuppression. HIV-infected AA with CRC presented with a higher percentage of left-sided CRC than AA's without HIV. Additionally, AAs with HIV tended to be younger at the time of CRC diagnosis. Our findings suggest that screening for CRC should be offered to HIV-infected AAs before the age of 45, and that sigmoidoscopy with fecal occult blood testing might be an acceptable screening modality. However, the exact age of initiation, optimal frequency, and preferred method of screening (colonoscopy vs. sigmoidoscopy) in this population requires further study.     

P53 germline mutations in childhood cancers and cancer risk for carrier individuals

The family history of cancer in children treated for a solid malignant tumour in the Paediatric Oncology Department at Institute Gustave-Roussy, has been investigated. In order to determine the role of germline p53 mutations in genetic predisposition to childhood cancer, germline p53 mutations were sought in individuals with at least one relative (first- or second-degree relative or first cousin) affected by any cancer before 46 years of age, or affected by multiple cancers. Screening for germline p53 mutation was possible in 268 index cases among individuals fulfilling selection criteria. Seventeen (6.3%) mutations were identified, of which 13 were inherited and four were de novo. Using maximum likelihood methods that incorporate retrospective family data and correct for ascertainment bias, the lifetime risk of cancer for mutation carriers was estimated to be 73% for males and nearly 100% for females with a high risk of breast cancer accounting for the difference. The risk of cancer associated with such mutations is very high and no evidence of low penetrance mutation was found. These mutations are frequently inherited but de novo mutations are not rare.     

Time trends of 16 modifiable risk factors on the burden of major cancers among the Chinese population

The cancer burden in China is increasing. We aimed to assess the time trends in the prevalence of 16 modifiable risk factors involved in lifestyle, diet, infection, and air pollution between 1997 and 2025 based on the China Health and Nutrition Survey, the Global Burden of Disease website, and publically available studies. The population attributable fraction (PAF) and its 95% uncertainty interval (UI) from 2007 to 2035 were calculated to quantify the attributable cancer burden in major 12 anatomic sites using the comparative risk assessment method, considering a 10-year lag effect. As a result, 1,559,476 cancer cases (PAF = 54.1%, 95% UI: 36.8%–65.8%) from the 12 anatomic sites were attributable to these modifiable risk factors in 2007, with lung, liver, and gastric cancer raging the top three. It was predicted that by 2035, the attributable cancer cases would reach 1,680,098 (PAF = 44.2%, 95% UI: 29.1%–55.5%), with the top three of lung, liver, and colorectal cancer. Smoking, physical inactivity, insufficient fruit consumption, HBV infection, and Helicobacter pylori infection were the most attributable risk factors in 2007, contributing to 480,352, 233,684, 215,009, 214,455, and 187,305 associated cancer cases, respectively. In 2035, the leading factors for cancer would be smoking, physical inactivity, insufficient fruit intake, HPV infection, and HBV infection, resulting in 427,445, 424,327, 185,144, 156,535, and 154,368 cancer cases, respectively. Intervention strategies should be swiftly established and dynamically altered in response to risk factors like smoking, physical inactivity, poor fruit intake, and infectious factors that may cause a high cancer burden in the Chinese population.     

Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: influence of rituximab.

BACKGROUND: The incidence of secondary central nervous system (CNS) occurrences in diffuse large-B-cell lymphoma is not sufficiently high to warrant the use of CNS prophylaxis in all patients. The addition of rituximab increases the complete response rate and prolongs event-free and overall survival in elderly patients with such lymphoma. PATIENTS AND METHODS: We analyzed a cohort of 399 elderly patients with lymphoma prospectively treated with eight cycles of CHOP with or without rituximab in order to assess if rituximab decreases the risk of CNS localization. Prophylaxis of CNS disease was not part of the treatment protocol. RESULTS: We observed 20 CNS occurrences: 12 on therapy, four after partial remission and four following complete remission. In three patients, the CNS was the only site of relapse. In a multivariate analysis, increased age-adjusted International Prognostic Index (IPI) was the only independent predictive factor of CNS recurrence. Only three of 20 patients are alive with a follow-up of 24 months. CONCLUSIONS: Rituximab did not influence the risk of CNS occurrence, possibly because of low rituximab diffusion. Direct intrathecal administration of rituximab could overcome this problem. We also confirmed that CNS occurrence is related to IPI as well as very poor prognosis of relapses occurring on therapy.     

Risk factors for leukemia occurrence among growth hormone users

A matched case-control study on leukemia occurrence among growth hormone (GH) users was performed to elucidate any risk factor for leukemia. The total doses of GH and administration of other hormones, such as thyroxine, gonadotropin, gonadal hormones, glucocorticoid and anabolic steroid, did not lead to any apparent difference between cases studied and controls. Neither doses of diagnostic X-rays nor therapeutic cranial irradiation was related to leukemia risk. Scintigraphy for thyroid function using radioactive iodide was the only significant risk factor (P = 0.03). Hematological changes and liver function before and one month after GH administration were compared and the cases studied showed more proliferative reaction of white blood cells with rapid increase of neutrophils, but lymphocyte response was variable. Lactic acid dehydrogenase, alkaline phosphatase, glutamic oxalacetic transaminase, glutamic pyruvic transaminase tended to decrease after GH treatment when the patients had shown abnormally increased levels. Other environmental and familial factors did not show any abnormal clusters.     

Salivary gland and nasopharyngeal cancers in individuals with acquired immunodeficiency syndrome in United States

Individuals with acquired immunodeficiency syndrome (AIDS) manifest an increased risk of cancer, particularly cancers caused by oncogenic viruses. Because some salivary gland and nasopharyngeal cancers are associated with Epstein Barr virus, the impact of AIDS on these cancers needs further evaluation. We used linked U.S. AIDS and cancer registry data (N = 519,934 people with AIDS) to derive standardized incidence ratios (SIRs) comparing risk of salivary gland and nasopharyngeal cancers to the general population. For salivary gland cancers (N = 43 cases), individuals with AIDS had strongly elevated risks for lymphoepithelial carcinoma (SIR 39, 95% CI 16–81) and squamous cell carcinoma (SIR 4.9, 95% CI 2.5–8.6). Among nasopharyngeal cancers (N = 39 cases), risks were elevated for both keratinizing and nonkeratinizing carcinomas (SIR 2.4, 95% CI 1.5–3.7 and SIR 2.4, 95% CI 1.2–4.4, respectively). The elevated risks of salivary gland and nasopharyngeal cancers among people with AIDS suggest that immunosuppression and oncogenic viral infections are etiologically important.