The Percentage of Cancer Caused By Infection

From: Viral Oncogenesis. H zur Hausen. In: Microbes and Malignancy. Infection as a cause of human cancer. J Parsonnet, ed. New York: Oxford University Press, 1999, pp 107-130. "If we limit our consideration to only those human cancers with a proven relationship to specific virus infections, approximately 15% of the worldwide cancer burden (with substantial geographic variation), emerges as caused by viruses, among them the second most frequent cancer in women, cervical cancer, and about 80% of liver cancers. This figure will almost double if other cancers currently associated with specific virus infections are proved to be caused by such agents."

In this estimate, the viruses directly linked to human tumors include Epstein-Barr virus (B-cell lymphomas [after immunosuppression], Burkitt's lymphoma, nasopharyngeal cancer, and some Hodgkin's disease and T-cell lymphomas); hepatitis B virus (hepatocellular carcinoma); papillomavirus types 5, 8, 14, 17, 20, & 47 (skin cancer in persons with epidermodysplasia verruciformis); papillomavirus types 16, 18, 31, 33, 35, 39, 45, 52, 56, 58 and a few others (cervical and anogenital cancer, and cancers of the tonsils and nailbeds); papillomavirus types 6 & 11 (verrucous carcinoma); and HTLV-1 (adult T-cell leukemia).

The potential human tumor viruses include not yet named novel papillomavirus types suspected in squamous cell carcinomas and basaliomas of the skin; HPV16, 18, 33, 57, 73 and others suspected in cancers of the oral cavity, tongue, larynx, nasal cavity, and esophagus and other head and neck sites; human herpesvirus 8 (Kaposi's sarcoma); hepatitis C virus (hepatocellular carcinoma and low-grade lymphomas); JC, BK, and SV40-like polyoma viruses (brain and pancreatic islet tumors, and mesotheliomas); human endogenous retrovirus HERV-K (seminomas and germ cell tumors such as testicular cancer); and adenoviruses.

The viruses indirectly involved in human tumors include HIV-I and II (Kaposi's sarcoma, B-cell lymphomas, and skin cancer); and herpes viruses including herpes simplex virus, cytomegalovirus, and varicella zoster virus (experimental data showing mutagenic activity and induction of DNA amplification of persisting polyoma- and papillomavirus DNA).

This estimate that 15% of cancer is caused by viruses is the same as zur Hausen's 1991 estimate. It dates from before it was determined that HPV is involved in nearly all cervical carcinomas, and that HBV and HCV are involved in nearly as high a percentage of hepatocellular carcinomas. Cervical and liver cancers were said to account for about 80 percent of virus-linked cancers at that time. Neither the old nor new estimates include gastric carcinomas caused by Epstein-Barr virus or by the bacterium Helicobacter pylori. And, the statement that "viruses must be thought of as the second most important risk factor for cancer development in humans, exceeded only by tobacco consumption," is founded in substantial part on false "smoking risks" caused by confounding by infection. An update is long overdue.

zur Hausen - Science 1991 abstract / PubMed

"Several kinds of viruses cause cancer in humans, accounting for 10-20% of cancer worldwide." (Viruses and human cancer. W Eckhart. Sci Prog 1998;81(Pt 4):315-328.)

Eckhart - Sci Prog 1998 abstract / PubMed

"Viruses are etiologically linked to approximately 20% of all malignancies worldwide." (Human retroviruses: their role in cancer. WA Blattner. Proc Assoc Am Physicians 1999 Nov-Dec;111(6):563-572.)

Blattner - Proc Assoc Am Physicians 1999 abstract / PubMed

"Infections may be responsible for over 15% of all malignancies worldwide." The authors acknowledge that Pisani et al.'s estimate that 52.6 to 59.5% of stomach cancer is caused by Helicobacter pylori is too low because "recent data indicate that the risk associated with the bacteria may have been underestimated due to spontaneous eradication in the precancerous stomach, potentially increasing the fraction of gastric cancer attributable to H. pylori to more than 75%." (Infections as a major preventable cause of human cancer. H Kuper, HO Adams, D Trichopoulos. J Intern Med 2000 Sep;248(3):171-183.) Note that even anti-smokers such as Dimitrios Trichopoulos, the author of studies blaming passive smoking for nonsmokers' lung cancer, and along with the two co-authors of this article, of a study blaming smoking for liver cancer whose deficient detection produces bogus "smoking risks" by confounding, must now admit that the evidence implicating infections in human cancer is growing. Now let's see Trichopoulos et al. address the issue of confounding by infection, and better still, of why investigation of the role of infection in nonsmokers' lung cancer has been neglected.

Kuper - J Intern Med 2000 abstract / PubMed
Kuper / J Intern Med 2000 full article

IARC 1997

The IARC has an obsolete estimate of only 16% of cancer worldwide caused by infection, including both viruses and bacteria. Its source is: Cancer and Infection: Estimates of the attributable fraction in 1990 (P Pisani, DM Parkin, N Munoz, J Ferlay. Cancer Epidemiol Biomarkers Prevent 1997 Jun;6(6):387-400). Revision according to the data cited by Kuper et al. would increase the percentage by about 2.6%. Pisani et al. also attribute only 82% of cervical cancer in developing countries, and 91% in developed countries, to human papillomavirus, when the correct figure should be 100%. This would increase the percentage by 0.9%. They do not include any cancers of the rectum, penis, head and neck, or esophagus among those caused by HPV. They wrongly attribute only 59% of liver cancer to hepatitis B, using HBsAg alone for prevalence of HBV infection, and odds ratios weakened by falsely blaming smoking: Contrary to their delusion, smoking is not a potential confounder. The claims against it are based on confounding by the infection. Most likely more than 95% of liver cancer is caused by either HBV or HCV, with the exception of those caused by schistosomes, which would increase the total by 0.8%. Only AIDS-related non-Hodgkin's lymphomas are attributed to EBV, and no gastric carcinomas. These would increase the total by at least 0.5%. No nasopharyngeal carcinoma is attributed to EBV, either, which would add 0.6%. With these additions, the worldwide total would be 21%.

It is claimed that most of the cancers caused by infection are in the undeveloped countries, and in the developed countries, the total is only 9.1%. With the above corrections, this would increase to about 12.4%. However, for socioeconomic reasons, there are higher rates of infection among smokers than nonsmokers, thus a higher proportion of cancer among smokers is due to infection.

Pisani - Cancer Epidemiol Biomarkers Prevent 1997 abstract / PubMed

The IARC still rants that "Smoking is now generally recognized as the most important preventable cause of human cancer" in its diatribe against the tobacco industry over the IARC ETS study, when that claim is based on corrupt science that falsely blames smoking for cancers caused by infection. It should be noted by all that the tobacco industry has never challenged this corrupt science. It is not reassuring of the scientific integrity of the IARC that the author of the ETS study in question, Dr. Boffetta, is also listed as the "responsible officer" for IARC courses such as the one on "Infections that increase the risk of cancer." It is clear that somebody ought to "interfere" to make them do things right, specifically, to consider the role of infection in nonsmokers' (and smokers') lung cancer which the health establishment has been stonewalling from the beginning.

IARC diatribe, "Tobacco industry interference with World Health Organization's research on passive smoke and cancer"

SAMMEC

The Office on Smoking and Health of the Centers for Disease Control claims that only 4% of deaths in the US are caused by infection, and that smoking causes "430,000" deaths. The purported basis for this claim is "Smoking-attributable mortality and years of potential life lost -- United States, 1984 (MMWR 1997 May 23;46(20):444-451). They simply ignore the role of infection in so-called "chronic" diseases such as cancer and cardiovascular disease, as per health fascist ideology, and pretend that only those deaths due to acute infection are caused by infectious agents. The only difference between the 1987 and the 1997 claims is that ulcers and stomach cancer were dropped from the list. The CDC lies that this was "because a causal relation has not been established," as if there might possibly be a causal relation established in the future, instead of the truth that those diseases were proven to be caused by infection, and the claims against smoking resulted from confounding; and that opinion against falsely blaming smoking was strong enough to force them to drop the claims. The CDC also lies that "a recent study has documented little change in SAM estimates after adjustment for confounders," falsely pretending that the "relevant confounders" are age, education, alcohol intake, diabetes, and hypertension, while ignoring the true confounder, infection. This is malicious trash, and those who peddle it to the public are liars and frauds.

Official lies from the CDC Office on Smoking and Health
MMWR 1997 (PDF) / CDC

Parkin 2006

The global health burden of infection-associated cancers in the year 2002. DM Parkin. Int J Cancer 2006 Jun 15;118(12):3030-3044. 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." No lung, bladder, or esophageal cancers were attributed to HPV. Only 85% of liver cancers were attributed to HBV and HCV; "the relative risk of liver cancer due to infection with hepatitis B is based on measurement of serum HBsAg. However, viral DNA can be found in many liver cancers without evidence of infection based on HBs antigenaemia or antibody to HCV." There is no mention of JCV. "The estimate of 17.8% updates the previous one of 14.8% cancer attributable to infection in 1990. The increased fraction results from the availability of more recent information on prevalence of infection with hepatitis viruses and HIV in different countries, as provided by WHO and UN AIDS, an assumption that the fraction of cervix cancer cases attributed to HPV is 100% rather than 88%. The risk associated with chronic infection with HP, previously assumed to be 2-fold, has also been set substantially higher (5.9). The infectious agents evaluated by IARC as definite or probable causes of human cancer (Groups I and 2A in the Monographs series) have remained more or less the same since that earlier estimate, with the exception that HHV-8 (KSHV) is now considered to be the probable cause of KS;50 previously, epidemic KS cases had been ascribed to HIV infection."

Parkin - Int J Cancer 2006 abstract / PubMed
Parkin - Int J Cancer 2006 full article / UCLA

The Centers for Disease Control, 2008

The CDC has finally admitted that HPV is an important cause of a number of human cancers, and prepared a parsimonious estimate, of 17,300 in women + 7,600 in men = 24,900 total. These include nearly all cervical cancers; 90% of anal; 40% of vulvar, vaginal and penile; 25% of mouth and 35% of throat cancers (in the cited study, 43.6% of tonsil, 38.4% base of tongue, and 18% of other oropharyngeal cancers were associated with HPV). "Cancer registries do not collect data on the presence or absence of HPV in cancer tissue at the time of diagnosis," so the estimates have been made by extrapolating the percentages found in laboratory studies to the incidence data from the cancer registries. (HPV-Associated Cancers. Division of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control. Accessed Feb. 17, 2009.) Cancers not mentioned include those of the lung, larynx, bladder, esophagus, and skin. HPV is implicated in at least a quarter of non-small cell lung cancers, and a large international study has found that 56.1% of esophageal cancers are positive for HPV. And, most important, there is no discussion of the fact that spurious results which falsely blame tobacco are inevitable in studies which are based on nothing but lifestyle questionnaires, nor of the fact that the percentage of cancers caused by infection may have been underestimated even in those studies which did.

HPV-Associated Cancers / CDC

Cancers Caused By Epstein-Barr Virus, NIH 2011

Epstein-Barr Virus: An Important Vaccine Target for Cancer Prevention. JI Cohen, AS Fauci, H Varmus, GJ Nabel. Sci Transl Med 2011 Nov 2;3(107):107fs7. "EBV is associated with a wide range of cancers that vary in incidence in different parts of the world. In the United States, Hodgkin lymphoma, non-Hodgkin lymphoma, and nasopharyngeal carcinoma are the most common EBV-positive malignancies. In Southern China, the rate of EBV-associated nasopharyngeal carcinoma is 50 per 100,000 in men over the age of 50 years. EBV-positive Burkitt lymphoma is the most common childhood tumor in equatorial Africa and New Guinea. Gastric carcinomas are prevalent in Eastern Asia, Eastern Europe, and South America, with nearly 1 million new cases each year worldwide, and although only ~9% are EBV-positive, this cancer is the most common EBV-associated malignancy worldwide. Chemotherapy is effective for many EBV-associated malignancies, but up to 50% of survivors of all forms of Hodgkin lymphoma die from chemotherapy-associated complications, secondary malignancies, or disease relapse."

Table 1. EBV by the numbers.

Estimated new cases of EBV-associated cancers worldwide per year (9, 10).

Cancer Number of cases Number of cases attributable to EBV
Burkitt lymphoma

Developed countries 400 100
Less-developed countries 7800 6600
Gastric carcinoma 933,900 84,050
Hodgkin lymphoma 62,400 28,600
Nasopharyngeal carcinoma 80,000 78,100
Total
197,450

Cohen / Sci Transl Med 2011 full article

The Percentage of Cancers Caused by HPV, CDC 2012

Overall, about 26,000 (18,000 among females and 8,000 among males) of 33,369 cancers at HPV-associated sites were attributed to HPV infection. For the individual cancers, the number and percentages attributable to HPV were:

Cervix, 11,500 (96%)
Vulva, 1,600 (51%)
Vagina, 500 (64%)
Penis, 400 (36%)
Anus (women), 2,900 (93%)
Anus (men), 1,600 (93%)
Oropharynx (women) 1,500 (63%)
Oropharynx (men), 5,900 (63%)

Estimates of the number of diagnoses are based on NPCR and SEER tumor registry data covering 100% of the U.S. population. "[B]ecause cancer registries typically do not capture information on HPV infection status, for this analysis, the average annual number of HPV-associated cancers was multiplied by the percentage of each cancer type found attributable to HPV based on genotyping studies." "Rates varied by state, with rates of HPV-associated cancers combined ranging from 8.5 per 100,000 (Utah) to 16.3 (West Virginia) among females, and from 4.9 (Utah) to 11.6 (District of Columbia) among males. Although rates varied by anatomic site, some states had lower or higher rates across cancer sites. Maryland, Colorado, and Utah had cancer rates in the lowest tertile for most or all HPV-associated cancers, whereas Kentucky, Louisiana, and Tennessee had rates in the highest tertile for most of the cancer sites." (Human Papillomavirus–Associated Cancers — United States, 2004–2008. MMWR 2012 Apr 20;61(15):258-261.) Again, cancers not mentioned include those of the lung, larynx, bladder, esophagus, and skin.

MMWR 2012 full article / CDC

See Also:

HPV Causes Lung Cancer HPV DNA has been detected in 24.5% of 4508 lung cancers [2009] and the same high risk types implicated in other squamous cell cancers have been identified. If HPV is the true cause of just 20% of lung cancers, this would equal over 30,000 US cases, or ten times the number of pretended secondhand smoke deaths.
JC Polyoma Virus Causes Colon Cancer JCV has been found in 89% of the most common type of colon cancer.
Confounding By Infection False smoking risks are generated by ignoring the role of infection.
The BIG LIE That Smoking is an Economic Burden to Society

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cast 07-05-12