Co-carcinogenesis: Human Papillomaviruses, Coal Tar Derivatives, and Squamous Cell Cervical Cancer.

Cervical cancer (CC) is the fourth most common cancers among women worldwide. Human papillomaviruses (HPVs) play a major role in the etiology of CC, with several lines of epidemiologic and experimental evidence supporting a role for non-viral (co-carcinogens) and host genetic factors in controlling the risk for progression to neoplasia among HPV-infected individuals. The role of co-carcinogens in the development of CC is significant in the developing world where poor sanitation and other socio-economic conditions increase the infectious cancer burden. Here, we discuss how exposure to environmental factors such as coal tar derivatives from cigarette smoking, tar-based sanitary products, and inhaled smoke from biomass-burning stoves, could activate host pathways involved in development of HPV-associated squamous cell cancers in resource-limited settings. Understanding interactions between these pathways with certain oncogenic HPV genotypes may guide implementation of strategies for control and treatment of HPV-associated cancers that develop in populations at high risk of exposure to various co-carcinogens.

Viruses, chemicals and co-carcinogenesis.

The etiology of cancers appears to be complex and multifactorial. Peyton Rous and others demonstrated the process of co-carcinogenesis by exposing rabbits to a virus and tars. Epidemiologists have proposed virus-chemical interactions to cause several cancers. For example, one might propose that the etiology of cervical cancer results from a complex interplay between oncogenic viruses and cervical tar exposures through tar-based vaginal douching, cigarette smoking, and/or long-term cooking over wood-burning stoves in poorly ventilated kitchens. Hepatocellular carcinoma may result from the joint effects of viruses and hepatotoxic chemical carcinogens. Kaposi's sarcoma might happen following reciprocal actions of human herpes virus-8 infection, immunosuppression, and chemical exposures, such as nitrite radicals and alumino-silicates. Use of Koch's postulates will not help one prove or disprove a multifactorial causation of disease; new criteria are needed. Delineating the web of causation may lead to additional strategies for prevention and treatment of several cancers.

Multifactorial etiology of cervical cancer: a hypothesis.

Cancer of the cervix is the second most common life-threatening cancer among women worldwide, with incidence rates ranging from 4.8 per 100,000 women per year in the Middle East to 44.3 per 100,000 in East Africa. Epidemiologic and clinical data demonstrate that human papillomaviruses (HPV), especially HPV-16 and HPV-18, play at least a major if not a necessary role in the etiology of cervical cancer. However, many investigators acknowledge that HPV is not sufficient to induce cervical cancer and that a multifactorial etiology is likely. HPV can be found in a growing proportion of patients with cervical cancer, approaching 100%, but is not yet found in every patient with disease. Other factors, such as herpes simplex virus type 2 infections, cigarette smoking, vaginal douching, nutrition, and use of oral contraceptives, have been proposed as contributing factors. In the first half of the 20th century, Peyton Rous and colleagues demonstrated the joint action of tars and Shope papillomavirus to consistently induce squamous cell carcinomas in rabbits. Using the Rous model as a prototype, one might hypothesize that some cases of cervical cancer arise from an interaction between oncogenic viruses and cervical tar exposures. Cervical tar exposures include cigarette smoking, use of tar-based vaginal douches, and long years of inhaling smoke from wood- and coal-burning stoves in poorly ventilated kitchens.

Cigarette smoking and cervical cancer: Part I: a meta-analysis.

Cancer of the cervix is the third most common cancer among women worldwide and its etiology is not clearly understood. Human papillomavirus can be found in approximately 95% of cervical cancers, but it does not appear to be necessary or sufficient to induce malignancy. In 1977, Winkelstein suggested that cigarette smoking was a causative factor in the development of cervical cancer. We report a meta-analysis of cigarette smoking and cervical disease and conclude that the data support a role for cigarette smoking as a risk factor for cervical cancer. We propose a multifactorial hypothesis involving a virus-tar interaction as the etiology of cervical cancer.

Enteroviruses and type 1 diabetes mellitus.

Despite decades of research, the etiology of type 1 diabetes mellitus (DM) is unknown. Several risk factors have been associated with type 1 DM, including viral infections, genetic predisposition, nutritional factors, and chemicals. Several investigators hypothesize that the etiologies of type 1 DM result from a complex interaction of genetic and environmental factors. In this paper we review the epidemiologic data linking enteroviruses to type 1 DM and discuss potential mechanisms of pathogenesis.

Cigarette smoking and cervical cancer: Part II: a geographic variability study.

Cigarette smoking is considered a causative factor in a variety of cancers. However, the role of smoking in cervical cancer is disputed, in part because women who smoke may have other risk factors for cervical cancer, particularly HPV infection. We reviewed cigarette smoking prevalence, cervical and lung cancer incidence, and gross domestic product (GDP) per capita in the US and 73 other countries. It appears that smoking may play a prominent role in cervical cancer in developing countries, but less of a role in other countries.

Adenovirus 36 antibodies associated with clinical diagnosis of overweight/obesity but not BMI gain: a military cohort study.

CONTEXT: Obesity is a public health priority, which also threatens national security. Adenovirus 36 (Adv36) increases adiposity in animals and Adv36 antibody status is associated with human obesity, but it is unknown whether infection predicts the development of human adiposity. OBJECTIVE: The objective of the study was to assess infection status and subsequent weight gain. DESIGN: The study had a retrospective cohort design. SETTING: The study was conducted at Air Force fitness testing and clinical encounters. PARTICIPANTS: PARTICIPANTS included Air Force male enlistees, aged 18-22 years, with a baseline body mass index (BMI) of 20-30 kg/m(2) followed up from enlistment (beginning in 1995) until 2012 or separation from the Air Force. EXPOSURE: EXPOSURE included Adv36 infection status at the time of entry. MAIN OUTCOME MEASURE: Follow-up BMI, the primary outcome, and diagnosis of overweight/obesity by the International Classification of Diseases, ninth revision V85.25+ and 278.0* series (secondary outcome) were recorded. RESULTS: The last recorded follow-up BMI was similar among infected and uninfected, 26.4 and 27.2 kg/m(2), respectively (P > .05). However, infected individuals had a higher hazard of a medical provider's diagnosis of overweight/obese over time (hazard ratio 1.8, 95% confidence interval 1.0-3.1, P = .04), adjusted for baseline BMI. Additionally, infected individuals who were lean at baseline (BMI of 22.5 kg/m(2)) had a 3.9 times greater hazard of developing an overweight/obese clinical diagnosis (95% confidence interval 1.5-9.7, P = .004) compared with uninfected lean individuals after adjusting for interaction (P = .03) between infection and baseline BMI. CONCLUSIONS: The presence of Adv36 antibodies was not associated with higher BMI at baseline or follow-up within this military population. However, being infected was associated with developing a clinical diagnosis of overweight/obesity, especially among those lean at baseline.

Viruses and vitamin D in the etiology of type 1 diabetes mellitus and multiple sclerosis.

Although specific viruses have been associated with autoimmune diseases, none fulfill Koch's criteria of causation. The etiologies of such diseases appear to be complex and multifactorial. For example, one might propose that the etiology of type 1 diabetes mellitus results from a toxic metabolite of nitrosamines during an enteroviral infection. Multiple sclerosis might result from a cascade of events involving several herpes virus infections activated during periods of vitamin D deficiency. We encourage investigators to consider Rotman's sufficient-component causal model when developing hypotheses for testing for the etiology of chronic diseases. Delineating the web of causation may lead to additional strategies for prevention and treatment of several autoimmune diseases.

Diagnostico y tratamiento del SIDA en los Estados Unidos / AIDS update: Medical diagnostic and treatment in United States

The acquired immunodeficiency syndrome (AIDS) continues to be a serious public health problem in the United States of America, especially for intravenous drug abuser (IVDA). Within this group the largest concentration of cases of the disease and of infection with the human immunodeficiency virus (HIV) is in New York, California, and New Jersey, but cases have been diagnosed and reported in all 50 of the states. HIV is readily spread from these users to their sexual companions and children in utero. It can be expected, at least over the next few years, that HIV seroprevalence rates and AIDS cases will continue to increase among IDVA. There is an increasingly urgent need to formulate, implement, and evaluate prevention strategies aimed at this group in particular. Extensive research is being devoted to the development of a safe and effective vaccine against HIV, as well as to the testing of possible antiviral agents. Unfortunately, those goals will no be attained in the immediate future; for the time being, the only means of controlling AIDS is to adopt the most effective possible measures in the areas of education and prevention

Diagnostico y tratamiento del SIDA en los Estados Unidos / AIDS update: Medical diagnostic and treatment in United States

The acquired immunodeficiency syndrome (AIDS) continues to be a serious public health problem in the United States of América, especially for intravenous drug abuser (IVDA). Within this group the largest concentration of cases of the disease and of infection with the human immunodeficiency virus (HIV) is in New York, California, and New Jersey, but cases have been diagnosed and reported in all 50 of the states. HIV is readily spread from these users to their sexual companions and children in utero. It can be expected, at least over the next few years, that HIV seroprevalence rates and AIDS cases will continue to increase among IDVA. There is an increasingly urgent need to formulate, implement, and evaluate prevention strategies aimed at this group in particular. Extensive research is being devoted to the development of a safe and effective vaccine against HIV, as well as to the testing of possible antiviral agents. Unfortunately, those goals will no be attained in the immediate future; for the time being, the only means of controlling AIDS is to adopt the most effective possible measures in the áreas of education and prevention