Representational difference analysis was used to isolate unique sequences present in more than 90 percent of Kaposi's sarcoma (KS) tissues obtained from patients with acquired immunodeficiency syndrome (AIDS). These sequences were not present in tissue DNA from non-AIDS patients, but were present in 15 percent of non-KS tissue DNA samples from AIDS patients. The sequences are homologous to, but distinct from, capsid and tegument protein genes of the Gammaherpesvirinae, herpesvirus saimiri and Epstein-Barr virus. These KS-associated herpesvirus-like (KSHV) sequences appear to define a new human herpesvirus.

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Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma

Pathology and genetics of tumours of the urinary system and male genital organs

Purpose Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus (HPV) infection, but empirical evidence is lacking. Patients and Methods HPV status was determined for all 271 oropharyngeal cancers (1984-2004) collected by the three population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping (Inno-LiPA), HPV16 viral load, and HPV16 mRNA expression. Trends in HPV prevalence across four calendar periods were estimated by using logistic regression. Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonrandom selection and to calculate incidence trends. Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses. Results HPV prevalence in oropharyngeal cancers significantly increased over ...

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Human Papillomavirus and Rising Oropharyngeal Cancer Incidence in the United States

Several infectious agents are considered to be causes of cancer in humans. The fraction of the different types of cancer, and of all cancers worldwide and in different regions, has been estimated using several methods; primarily by reviewing the evidence for the strength of the association (relative risk) and the prevalence of infection in different world areas. The estimated total of infection-attributable cancer in the year 2002 is 1.9 million cases, or 17.8% of the global cancer burden. The principal agents are the bacterium Helicobacter pylori (5.5% of all cancer), the human papilloma viruses (5.2%), the hepatitis B and C viruses (4.9%), Epstein-Barr virus (1%), human immunodeficiency virus (HIV) together with the human herpes virus 8 (0.9%). Relatively less important causes of cancer are the schistosomes (0.1%), human T-cell lymphotropic virus type I (0.03%) and the liver flukes (0.02%). There would be 26.3% fewer cancers in developing countries (1.5 million cases per year) and 7.7% in developed countries (390,000 cases) if these infectious diseases were prevented. The attributable fraction at the specific sites varies from 100% of cervix cancers attributable to the papilloma viruses to a tiny proportion (0.4%) of liver cancers (worldwide) caused by liver flukes.

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The global health burden of infection-associated cancers in the year 2002.

Background DNA fragments that appeared to belong to an unidentified human herpesvirus were recently found in more than 90 percent of Kaposi's sarcoma lesions associated with the acquired immunodeficiency syndrome (AIDS). These fragments were also found in 6 of 39 tissue samples without Kaposi's sarcoma, including 3 malignant lymphomas, from patients with AIDS, but not in samples from patients without AIDS. Methods We examined the DNA of 193 lymphomas from 42 patients with AIDS and 151 patients who did not have AIDS. We searched the DNA for sequences of Kaposi's sarcoma–associated herpesvirus (KSHV) by Southern blot hybridization, the polymerase chain reaction (PCR), or both. The PCR products in the positive samples were sequenced and compared with the KSHV sequences in Kaposi's sarcoma tissues from patients with AIDS. Results KSHV sequences were identified in eight lymphomas in patients infected with the human immunodeficiency virus. All eight, and only these eight, were body-cavity–based lymphomas — that...

Kaposi's Sarcoma–Associated Herpesvirus-Like DNA Sequences in AIDS-Related Body-Cavity–Based Lymphomas

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(97)09028-4.pdf

Spectrum of AIDS-associated malignant disorders

*This article is a US Government work and, as such, is in the public domain of the United States of America. Knowledge of the embryology and microscopic anatomy of the ovary is fundamental to the understanding of the various cancer types that originate in this organ. A complete description of the embryology and anatomy of the ovary is beyond the scope of this monograph; however, comprehensive reviews are available for those who seek more detail. The current discussion focuses on key developmental events and anatomic features that shed light on the natural history of ovarian cancers. At approximately five weeks of gestation, thickenings of the lining of the posterior embryonic body cavity, the coelomic epithelium, form the genital ridges. Continued proliferation of the coelomic epithelium into the underlying primitive connective tissue, known as the mesenchyme, leads to the formation of the primordial indifferent gonads. Cells from adjacent transient embryonic structures, known as mesonephros, concurrently invade the mesenchyme, and the primordial germ cells arrive after a long journey that starts at their place of origin in the yolk sac and takes the cells along the distal embryonic intestine and the posterior wall of the embryonic body cavity. The different tumor types that arise in the ovary are linked to the different cell types that are present at this stage of development: coelomic epithelial, mesenchymal, mesonephric, and germ cells. Ovaries and testes develop in similar fashion until approximately the fourth month of embryonic life. This finding explains the origin of tumors that are commonly associated with testicular tissue but appear in the ovaries and vice versa. At two months gestation, the primitive gonad is recognized as an ovary because of the lack of development of the well-defined testicular sex cords. Instead, mesonephric cells and germ cells remain closely associated, forming illdefined ovarian sex cords embedded in the primitive mesenchyme. The coelomic epithelium remains at the periphery, enwrapping the developing ovary. In the adult, the ovaries are flat, nodular, oval structures that measure between 3 and 5 cm in their greatest dimension and weigh between 2 and 4 g. They are suspended by peritoneal folds and ligaments on either side of the uterus and attached to the back of the broad ligament of the uterus, behind and below the uterine tubes. A single layer of cells, the surface epithelium, which is derived from the coelomic epithelium, lines their external surface. A dense, fibrous tissue, the stroma, which is derived from the mesenchyme, makes up most of their internal substance. The germ cells, also known as oocytes, are located near the periphery of the stroma. The granulosa cells, specialized cells of probable mesonephric origin that are derived from the sex cords, surround the germinal cells that form the follicles. The stroma immediately surrounding the follicles differentiates into plum elongated cells known as theca cells. When stimulated, theca 2631

Pathology and classification of ovarian tumors.

We describe the anatomic and histologic presentation and prognosis of non-Hodgkin's lymphoma (NHL) among people with AIDS (PWA) and determine their contribution to the NHL burden. We linked AIDS and cancer registries in selected areas of the United States and compared NHL sites and histologies in PWA and non-PWA, after adjusting for age, sex and ethnicity. Among 51,033 PWA, we found 2,156 cases of NHL (4.3%). Half of NHL cases occurring post-AIDS were not reported to AIDS registries. NHL was part of an AIDS-defining condition for 3.2% of all PWA; the relative risk of NHL with 3.5 years of another AIDS diagnosis was 165-fold compared to non-PWA within the cancer surveillance system. Of NHLs, 39% were high grade (vs. 12% among non-PWA), 60% were nodal (vs. 74% among non-PWA) and 15% had brain primaries (vs. 1% among non-PWA). Excluding brain sites, extranodal sites were still 20% more common than expected. Relative risk was elevated for all histologic types, with the risk ranging from 652-fold for high-grade diffuse immunoblastic tumors and 261-fold for Burkitt's lymphomas to 113 for intermediate-grade lymphoma to 14-fold for low-grade lymphoma. Survival among PWA with NHL was poor, and tumor grade had little impact. In high-risk AIDS areas, AIDS-related NHLs constitute a major share of the NHL burden. We conclude that NHL risk is considerably under-estimated in AIDS registry data. The major differences between PWA and non-PWA were the high frequency of brain lymphoma and the increase in high-grade lymphomas in PWA. However, the grade of NHL did not influence the prognosis among PWA with lymphoma. The increasing risk of NHL in PWA has contributed substantially to the general increase in NHL rates in the United States since 1981.

Non‐Hodgkin's lymphoma among people with AIDS: Incidence, presentation and public health burden

High incidence of anal cancer among AIDS patients

Background : In recent years, brain lymphoma incidence has dramatically increased, presumably because of elevated risk of brain lymphoma among persons with acquired immunodeficiency syndrome (AIDS). Purpose : The objective of this study was to estimate independent incidence and survival rates of brain lymphoma among persons with or without AIDS and to understand the epidemiologic features of this cancer. Methods : We linked AIDS and cancer registry reports at nine state and local health departments and compared the demographics, histology, and survival of brain lymphoma cases among persons with or without AIDS. The data were limited to people under 70 years of age. We calculated the incidence of brain lymphoma among persons with AIDS and compared observed cases with those expected. The differences were statistically analyzed using the Poisson test. Epidemiologic features of brain lymphoma in persons with or without AIDS were compared using the chi-squared test, the Student's t test, and the chi-squared test for linear trend. The logrank test was used to compare survival rates estimated by the Kaplan-Meier technique. All P values were two-sided. Results : We matched 50 989 AIDS registry reports to 859 398 cancer registry reports (data from 1981 to 1990) and found 431 people with both AIDS and brain lymphoma. Among people with AIDS, those developing brain lymphoma versus those without brain lymphoma were more likely to be white (70% versus 59% ; P<.001) and had homosexuality as their only human immunodeficiency virus risk factor (75% versus 64% ; P<.001). Of the 431 patients, 223 developed brain lymphomas during 47465 person-years of observation after diagnosis of AIDS. The absolute incidence rate of brain lymphoma among persons with AIDS was 4.7/1000 person-years (95% confidence interval = 4.1-5.3/1000 person-years), 3600-fold higher than the base-line rate in the general population. From 1980 through 1989, overall counts of brain lymphoma increased ninefold. Most of this increase was derived from persons with AIDS, but a substantial increase also occurred among persons without AIDS (0.04/100 000 in 1982 to 0.28/100 000 in 1989) (chi-squared test for trend ; P<.05). The median survival was shortest for persons with AIDS and brain lymphoma (2 months), was intermediate for persons with brain lymphoma without AIDS (5-7 months), and was longest for persons with AIDS without brain lymphoma (14 months) (P<.05 for all comparisons). Conclusions: This analysis distinguishes the separate epidemiologies of brain lymphoma incidence among persons with or without AIDS and shows brain lymphoma incidence among persons with AIDS to be several thousand-fold higher than that in the general population. The study documents the overwhelming effect of AIDS-associated brain lymphoma on the overall rate in the general population and demonstrates a significantly rising trend, although of a lesser magnitude, among persons without AIDS. Implications : This study emphasizes a greater need to bring health care resources to this burgeoning epidemic.

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Timothy R. Coté

Papers

Spectrum of AIDS-associated malignant disorders

Pathology and classification of ovarian tumors.

Non‐Hodgkin's lymphoma among people with AIDS: Incidence, presentation and public health burden

High incidence of anal cancer among AIDS patients

Epidemiology of Brain Lymphoma Among People With or Without Acquired Immunodeficiency Syndrome