HPV Causes Lung Cancer

Since the 1980s, a small but steady trickle of research (mostly non-U.S.) has implicated human papillomaviruses as a cause of lung cancer. HPV DNA has been detected in 24.5% of non-small cell lung cancers. It was not established that HPV causes 100% of cervical cancers until 1999, and in they only looked for a few high-risk types, so the prevalence of HPV is certainly underestimated in these early studies. If HPV is the true cause of only 20% of lung cancers, this would equal over 30,000 US cases, or ten times the number of pretended secondhand smoke deaths, annually. This is also nearly three times more than the approximately 12,000 (CDC) new cervical cancers in the U.S.! Because smokers and passive smokers are more likely to have been exposed to this virus, the anti-smokers' studies, which are based on nothing but lifestyle questionnaires, automatically falsely blame the extra lung cancers caused by HPV on smoking and passive smoking. The health establishment has officially ignored the implications of this research, including the Surgeon General, the US Environmental Protection Agency, and the California EPA, in their reports on smoking and secondhand smoke. Therefore, these officials are guilty of scientific fraud.

Proof of Conspiracy to Conceal the Role of Viruses in Lung Cancer: The latest anti-smoker propaganda claims that "Scientists may have found a way to tell which smokers are at highest risk of developing lung cancer: measuring a telltale genetic [sic] change inside their windpipes." Dr. Avrum Spira et al. found that some current or former smokers with lung cancer or precancerous lesions had higher activity of a certain enzyme in their upper airways than those who didn't. "[T]he genes involved were part of a well-known cancer-causing pathway named the PI3K pathway. When PI3K-related genes are too active, too much cell growth can occur, but most studies have examined those genes only in tumors." Six of nine patients treated with experimental drugs had there lesions improve. It's dressed up with deceitful rhetoric that "Smoking bathes the entire respiratory tract in toxins." (Developing test to warn smokers of cancer danger. By Lauran Neergaard, AP Medical Writer, Apr. 8, 2010.)

BUT - What they're testing for, activation of the PI3K system, is actually a sign of virus infection. "A number of viruses including EBV, HPV, HBV and HCV have the ability to establish long-term infections in the host, either through the establishment of latent or chronic infections, which can ultimately lead to cellular transformation. It appears that the gene products of these viruses stimulate PI3K–Akt-mediated cell survival and thereby block apoptosis of the cells they infect. This contributes to both virus survival and oncogenic transformation..." (The pivotal role of phosphatidylinositol 3-kinase–Akt signal transduction in virus survival. S Cooray. J Gen Virol 2004;85:1065-1076.)

Spira et al. attempt to implicate smoking by rhetorical means (the word "smokers" appears 76 times), without any supporting evidence that smoking activates the PI3K pathway. To the contrary, they admit in the discussion that "this increased activity is independent of smoking status or other smoking-related disease." The only virus mentioned was a recombinant adenovirus used in a standardization exercise. (Airway PI3K Pathway Activation Is an Early and Reversible Event in Lung Cancer Development. AM Gustafson, R Soldi, C Anderlind, MB Scholand, J Qian, X Zhang, K Cooper, D Walker, A McWilliams, G Liu, E Szabo, J Brody, PP Massion, ME Lenburg, S Lam, AH Bild, A Spira. Sci Transl Med 2010 Apr 7;2(26):26ra25.)

Human papillomavirus can escape immune recognition through Langerhans cell phosphoinositide 3-kinase activation. SC Fausch, LM Fahey, DM Da Silva, WM Kast. J Immunol 2005 Jun 1;174(11):7172-7178. "Langerhans cells (LC), which are located at the sites of primary infection, do not induce a response implicating the targeting of LC as an immune escape mechanism used by HPV. LC incubated with HPV virus-like particles up-regulate the phosphoinositide 3-kinase (PI3-K) pathway and down-regulate MAPK pathways. With the inhibition of PI3-K and incubation with HPV virus-like particles, LC initiate a potent HPV-specific response."

The Empire strikes back: The health establishment once commissioned studies claiming that EBV could not be found in nasopharyngeal carcinomas in western countries, and hence played no role, outside of Asia. This lie died because EBV activity turned out to be a crucial factor in prognosis and treatment. They are now pulling the same trick about HPV and lung cancer.

Studies of HPV and Lung Cancer

Human papillomavirus type 16 related DNA in an anaplastic carcinoma of the lung. A Stremlau, L Gissman, H Ikenberg, M Stark, P Bannasch, H zur Hausen. Cancer 1985 Apr 15;55(8):1737-1740. HPV16 in 1/24 (4%) lung carcinomas of various types.

Human papillomavirus DNA in bronchial squamous cell carcinomas. KJ Syrjanen, SM Syrjanen. Lancet 1987 Jan 17;1(8525):168-169. Reported in Syrjanen 2001: 5 out of 99 were positive for HPV 16/18 by ISH.

A survey of human cancers for human papillomavirus DNA by filter hybridization. RS Ostrow, DA Manias, WJ Fong, KR Zachow, AJ Faras. Cancer 1987 Feb 1;59(3):429-434. "Approximately 2%" of 217 malignancies contained HPV DNA of then-known types by hybridization.

Human papillomavirus (HPV) type 6 and 16 DNA sequences in bronchial squamous cell carcinomas demonstrated by in situ hybridization. K Syrjanen, S Syrjanen, J Kellorski, J Karja, R Mantyrjarvi. Lung 1989;167:33-42. 12/131 (9%) by probe, 9 of which contained sequences from the tested HPV types 6, 11, 16, 18 or 30. Funded by the Finnish Cancer Society, by PHS grant number 5 R01 CA 42010 of the National Cancer Institute; and by the Social Insurance Institution of Finland.

Detection of human papillomavirus DNA in squamous bronchial metaplasia and squamous cell carcinomas of the lung by in situ hybridization using biotinylated probes in paraffin embedded specimens. F Bejui-Thivolet, N Liagre, MC Chignol, Y Chardonnet, LM Patricot. Hum Pathol 1990 Jan;21(1):111-116. 6/33 (18%) of squamous cell carcinomas were HPV+.

Survey of histologic specimens of human cancer for human papillomavirus types 6/11/16/18 by filter in situ hybridization. JK Kulski, T Demeter, S Mutavdzic, GF Sterrett, KM Mitchell, EC Pixley. Am J Clin Pathol 1990 Nov;94(5):566-570. 2/5 lung carcinomas of unspecified type were HPV+ by FISH.

Occurrence of human papillomavirus DNA in primary lung neoplasms. SA Yousem, NP Ohori, E Sonmez-Alpan. Cancer 1992 Feb 1;69(3):693-697. 6/20 squamous cell, 1/6 undifferentiated carcinoma were HPV positive; types 6/11, 16/18, and 31/33/35 were tested for. 0/32 adenocarcinomas, bronchioalveolar, or small cell carcinomas were positive.

Human papillomavirus DNA in squamous cell carcinomas of the respiratory and upper digestive tracts. H Ogura, S Watanabe, K Fukushima, Y Masuda, T Fujiwara, Y Yabe. Jpn J Clin Oncol 1993 Aug;23(4):221-225. "HPV DNA of types 16 and/or 18 was detected using the polymerase chain reaction (PCR) method in 16 out of 121 cases (13.2%). By Southern blot hybridization, however, only the DNA from a laryngeal and a tonsillar carcinoma was found to hybridize with the whole HPV 16 DNA probe (two out of 16 HPV DNA-positive cases by PCR, 12.5%). None of the DNAs hybridized with the whole HPV 18 DNA probe. The discrepancy in the results of PCR and Southern blot hybridization methods seemed to reflect their sensitivity."

Human papillomavirus (HPV) infections in carcinogenesis of the upper aerodigestive tract. K Syrjanen & Kuopio Papillomavirus Research Group (S Syrjanen, R Mantyjarva, S Saarikoski, F Chang, S Parkkinen, M Yliskoski, T Nurmi, V Kataja, J Kellokoski, M Hippelainen, A Tervahauta, J Janne, L Albonen). Research proposal to the Council for Tobacco Research, estimated date 1993. The CTR's Kuopio Papillomavirus Research Group's projects were practically the only work investigating infection as the fundamental cause of disease.

[Detection of human papillomavirus DNA in squamous cell carcinomas of the lung by multiple polymerase chain reaction]. LQ Xing, HR Liu, JY Si. Zhonghua Jie He He Hu Xi Za Zhi 1993 Oct;16(5):275-277, 319. 7/49 (14.2%) were HPV positive, types 6/11 and 16.

Development of a broad spectrum PCR assay for papillomaviruses and its application in screening lung cancer biopsies. V Shamanin, H Delius, EM de Villiers. J Gen Virol 1994 May;75(pt 5):1149-1156. 0/85 HPV+.

Human papillomavirus not found in squamous and large cell lung carcinomas by polymerase chain reaction. I Szabo, R Sepp, K Nakamoto, M Maeda, H Sakamoto, H Uda. Cancer 1994 Jun 1;73(11):2740-2744. 0/40 squamous, 0/7 large cell carcinomas HPV-positive, types 6, 11,16, 18, 31, 33, 52b, and 58 were tested for. Comment in: KM Fong, J Schonrock, IM Frazer, PV Zimmerman, PJ Smith. Cancer 1995 May 1;75(9):2400-2401. No abstract.

[A study of human papillary virus infection by in situ hybridization and histopathology in squamous cell carcinomas of the lung]. HR Liu, LQ Xing, JY Si. Zhonghua Bing Li Xue Za Zhi 1994 Oct;23(5):299-301. Same tumors as Xing 1993; 5/7 positive by PCR were confirmed by ISH.

Prognostic importance of human papilloma virus typing in squamous cell papilloma of the bronchus: comparison of in situ hybridization and the polymerase chain reaction. HH Popper, Y el-Shabrawi, W Wockel, G Hofler, L Kenner, FM Juttner-Smolle, MG Pongratz. Hum Pathol 1994 Nov;25(11):1191-1197. "Thirty-one solitary bronchial squamous cell papillomas (SCPs) with variable degrees of dysplasia, one combined with larynx papilloma and small cell carcinoma in the contralateral lung, and 12 papillomas combined with invasive squamous cell carcinomas (SCCs) were investigated for the presence of human papilloma virus (HPV) DNA by in situ hybridization (ISH) and the polymerase chain reaction (PCR). Benign SCPs showed an association with HPV type 11 and rarely with type 6, whereas type 16 or 18, sometimes in combination with type 31/33/35, was found in SCPs associated with SCCs. In one patient HPV type 18- and 31/33/35-positive benign SCP preceded the recurrence of HPV 18-positive SCP (this time combined with carcinoma) by 2 years. Patients with SCP exhibiting HPV 16 or 18 positivity are at high risk for the development of SCC."

[Analysis of the characteristics of human papillomavirus infection in 85 neoplasms of the respiratory system in adult patients]. LQ Xing, HR Liu, JY Si. Zhonghua Zhong Liu Za Zhi 1994 Nov;16(6):424-427. 7/49 (14.2%) of squamous cell lung carcinomas were HPV positive.

Human papillomavirus type 18 DNA and E6-E7 mRNA are detected in squamous cell carcinoma and adenocarcinoma of the lung. I Kinoshita, H Dosaka-Akita, M Shindoh, M Fujino, K Akie, M Kato, K Fujinaga, Y Kawakami. Br J Cancer 1995 Feb;71(2):344-349. 1/10 (10%) of squamous cell, 2/22 (9%) of adenocarcinomas were HPV-18+.

[Detection of human papillomavirus type 16, 18, and 33 DNA in stage I (pT1N0M0) squamous cell carcinoma of the lung by ploymerase chain reaction]. M Sagawa, Y Saito, C Endo, M Sato, K Usuda, K Kanma, S Takahashi, E Chin, A Sakurada, K Aikawa, et al. Kyobu Geka 1995 May;48(5):360-362. By PCR, "Human papillomavirus type 18 was present in 1 case (12.5%) in contrast that type 16 and 33 were not detected in these cases."

Human papillomavirus DNA and TP53 mutations in lung cancers from butchers. AA al-Ghamdi, CM Sanders, M Keefe, D Coggon, NJ Maitland. Br J Cancer 1995 Aug;72(2):293-297. 1/8 squamous cell carcinomas were HPV positive; types 16, 18 and 33 were tested for by PCR.

Detection of human papillomavirus types 16, 18 DNA related sequences in bronchogenic carcinoma by polymerase chain reaction. Q Li, K Hu, X Pan, Z Cao, J Yang, S Hu. Chin Med J (Engl) 1995 Aug;108(8):610-614. "HPV 16, 18 DNA related sequences were found in 32% of lung cancer specimens, with 10 cases of HPV 16, 5 cases of HPV 18 and 1 case of both types. 48.15% (13/27) of squamous cell carcinomas were shown to be positive for HPV 16, 18 DNA. In addition, two adenocarcinomas and one small cell carcinoma were positive for HPV 16 DNA. No specimens from benign diseases tissues and fetal lung tissues showed positive results. These results suggest that primary bronchogenic carcinoma is related to HPV infection."

[Point mutation of p53 and detection of human papillomavirus DNA in bronchogenic carcinoma]. X Zhang, Y Zhu, L Li. Zhonghua Nei Ke Za Zhi 1995 Oct;34(10):673-675. 4/34 HPV+, all 4 were squamous cell; HPV types tested for were not specified in the abstract.

Detection of human papillomavirus DNA in primary lung carcinoma by nested polymerase chain reaction. P Thomas, X De Lamballerie, L Garbe, H Douagui, JP Kleisbauer. Cell Mol Biol (Noisy-le-grand) 1995 Dec;41(8):1093-1097. Types 6/11, 16 and 18 found in 2/18 (11%) of squamous cell, 1/4 adenocarcinomas, 2/7 neuroendocrine, 0/2 large cell.

p53 protein accumulation and the presence of human papillomavirus DNA in bronchiolo-alveolar carcinoma correlate with poor prognosis. K Nuorva, Y Soini, D Kamel, R Pollanen, R Bloigu, K Vahakangas, P Paakko. Int J Cancer 1995 Dec 20;64(6):424-429. HPV types 6, 11, 16, 18, 31, and 33 were tested for; 36% (8) of 22 bronchiolo-alveolar carcinomas were positive.

[Human papillomavirus infection and p53 gene mutation in primary lung cancer]. J Da, L Chen, Y Hu. Zhonghua Zhong Liu Za Zhi 1996 Jan;18(1):27-29. "HPV-DNA positive rate in lung cancer was 55% (22/40 cases), including SCLC (9/9 cases), squamous cell carcinomas (8/16 cases), and adenocarcinomas (5/12 cases)... SCLC and squamous carcinoma had higher HPV infection rate than other types of lung cancer."

Detection of human papilloma virus (HPV) and K-ras mutations in human lung carcinomas. A Noutsou, M Koffa, M Ergazaki, et al. Int J Oncol 1996;8:1089–1093. No abstract. Reported in Syrjanen 2001: 8 out of 41 (20%) adenocarcinomas were positive for HPV (2 type 16, 6 type 18) by PCR.

Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma. Y Soini, K Nuorva, D Kamel, R Pollanen, K Vahakangas, VP Lehto, P Paakko. Thorax 1996 Sep;887-893. HPV types 6, 11, 16, 18, 31, and 33 were tested for, 13/43 (30%) were positive, tumor types not stated in the abstract.

Human papillomavirus DNA in squamous cell carcinoma of the lung. T Hirayasu, T Iwamasa, Y Kamada, Y Koyanagi, H Usuda, K Genka. J Clin Pathol 1996 Oct;49(10):810-817. Higher percentage of HPV+ in Okinawa than Niigata (79% versus 30% by PCR), despite similar smoking rates. "The detection of HPV DNA was strongly associated with well differentiated SCC. This was particularly true for HPV types 6 and 16. There was no correlation between either smoking and detection of HPV DNA, or smoking and histological differentiation."

[Detection of human papillomavirus by polymerase chain reaction in primary lung carcinoma]. P Thomas, X De Lamballerie, L Garbe, O Castelnau, JP Kleisbauer. Bull Cancer 1996 Oct;83(10):842-846. HPV types 6/11, 16 and 18 were found in 2/18 (11%) of squamous cell, 1/4 adenocarcinomas, 1/6 small cell, and 1/1 neuroendocrine carcinomas.

Human papillomavirus infection is not associated with bronchial carcinoma: evaluation by in situ hybridization and the polymerase chain reaction. A Welt, M Hummel, G Niedobitek, H Stein. J Pathol 1997 Mar;181(3):276-280. 0 of 38 (32 squamous cell carcinomas (SCCs) and six small cell carcinomas of the bronchus) were positive for HPV types 6, 11, 16 or 18 by PCR and ISH.

Carcinoma of the lung in Okinawa, Japan: with special reference to squamous cell carcinoma and squamous metaplasia. I Nakazato, T Hirayasu, Y Kamada, K Tsuhako, T Iwamasa. Pathol Int 1997 Oct;47(10):659-672. "The authors postulate that HPV infects adenocarcinoma cells and changes them to enlarged cells, followed by squamous metaplasia. In this report, HPV DNA was transfected to adenocarcinoma cells (cultured cell lines) and this showed that HPV causes squamous metaplasia."

Detection of human papillomavirus in squamous cell carcinomas of the lung by polymerase chain reaction. T Bohlmeyer, TN Le, AL Shroyer, N Markham, KR Shroyer. Am J Respir Cell Mol Biol 1998 Feb;18(2):265-269. University of Colorado; 2/34 positive, types 6, 11, 16, 18 and 33 tested for. The authors are oblivious to the significance of improvements in HPV detection, and also engage in unsupported speculation about the role of smoking. For example, while they claim that "in the cigarette smoker, in contrast to the nonsmoker, the lower respiratory tract will often have numerous squamo-columnar junctions which could serve as 'fertile soil' for infection by HPV," they failed to find this HPV, although all 34 were said to be smokers or ex-smokers. This is an ATS (ALA) journal, so perhaps that explains a lot.

Detection of human papillomaviruses in squamous cell carcinomas of the lung. K Papadopoulou, V Labropoulou, P Davaris, P Mavromara, H Tsimara-Papastamatiou. Virchows Arch 1998 Jul;433(1):49-54. Athens, Greece; 35/52 (69%) of squamous cell carcinomas were positive for HPV types 6/11 and 16/18.

Human papillomavirus DNA in adenosquamous carcinoma of the lung. K Tsuhako, I Nakazato, T Hirayasu, H Sunakawa, T Iwamasa. J Clin Pathol 1998 Oct;51(10):741-749. 8 out of 207 cases (78.3%) in Okinawa, were HPV positive. Types 6, 11, 16 and 18 were found.

High-risk human papillomavirus types and squamous cell carcinoma in patients with respiratory papillomas. CE Moore, RJ Wiatrak, KD McClatchey, CF Koopmann, GR Thomas, CR Bradford, TE Carey. Otolaryngol Head Neck Surg 1999 May;120(5):698-705. "We found that RPs may have either low- or high-risk HPV types and some contain multiple HPV types. Respiratory infection with high-risk HPV apparently introduces a long-term risk of squamous cell carcinoma development, even in the absence of conventional cofactors. Low-risk HPV infection may also act in association with these cofactors to promote carcinogenesis."

HPV positive bronchopulmonary carcinomas in women with previous high-grade cervical intraepithelial neoplasia (CIN-III). EM Hennig, Z Suo, F Karlsen, R Holm, S Thoresen, JM Nesland. Acta Oncol 1999;38(5):639-647. 37/75 (49%) of primary bronchopulmonary tumors were HPV positive by PCR.

Detection of human papillomavirus DNA in bronchopulmonary carcinomas by hybrid capture II: a study of 185 tumors. CE Clavel, B Nawrocki, B Bosseaux, G Poitevin, IC Putaud, CC Mangeonjean, M Monteau, PL Birembaut. Cancer 2000 Mar 15;88(6):1347-1352. 5/185 (2.7%; 3 males, 2 females) were HPV positive, using cervical-type test. From the American Cancer Society.

Prognostic implication of human papillomavirus infection in squamous cell carcinoma of the lung. T Iwamasa, J Miyagi, K Tsuhako, T Kinjo, Y Kamada, T Hirayasu, K Genka. Pathol Res Pract 2000;196(4):209-218. Okinawa: "The prognosis of HPV-infected cases was found to be better than that of the non-infected cases... However, among the virus-infected cases, the type 16 virus-infected cases showed a poorer prognosis, compared to those infected with other HPV types."

Recent striking change in histological differentiation and rate of human papillomavirus infection in squamous cell carcinoma of the lung in Okinawa, a subtropical island in southern Japan. J Miyagi, K Tsuhako, T Kinjo, T Iwamasa, T Hirayasu. J Clin Pathol 2000 Sep;53(9):676-684. "The decreasing incidence of viral infection correlates strongly with the falling numbers of SCC cases, especially well differentiated cases." (An increasing proportion of adenocarcinoma versus squamous cell carcinoma has been previously noted in Western countries.)

[Detection and significance of HPV16, 18 infection, P53 overexpression and telomerase activity in patients with lung cancer]. H Niyaz, C Zhao, Y Li. Zhonghua Jie He He Hu Xi Za Zhi 2000 Nov;23(11):679-682. 110 specimens of lung cancer. "The positive rate of HPV16, 18-DNA in the lung cancer group was higher than the normal tissues group and inflammatory lesions group (all P < 0.01)." No other details in abstract.

Detection of human papillomavirus in non-small cell lung carcinoma by polymerase chain reaction. A Miasko, W Niklinska, J Niklinski, E Chyczewska, W Naumnik, L Chyczewski. Folia Histochem Cytobiol 2001;39(2):127-128. High risk HPV was found in 1/22 squamous cell, 1/5 large cell, 1/13 adenocarcinomas; low risk HPV found in 1 adenocarcinoma.

Extremely high Langerhans cell infiltration contributes to the favourable prognosis of HPV-infected squamous cell carcinoma and adenocarcinoma of the lung. J Miyagi, T Kinjo, K Tsuhako, M Higa, T Iwamasa, Y Kamada, T Hirayasu. Histopathology 2001 Apr;38(4):355-367. HPV was detected in 12 cases (19.4%) of 62 adenocarcinomas, and in 29 cases (49.2%) of 59 squamous cell carcinomas. "Furthermore, there was no significant correlation between either Langerhans cell infiltration and smoking, or HPV infection and smoking, in either squamous cell carcinoma or adenocarcinoma cases."

The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women. Y-W Cheng, H-L Chiou, G-T Sheu, L-L Hsieh, J-T Chen, C-Y Chen, J-M Su, H Lee. Cancer Res 2001 Apr 1;61(7):2799-2803. "77 (54.6%) of 141 lung tumors had HPV 16/18 DNA compared with 16 (26.7%; P = 0.0005) of 60 noncancer control subjects. In addition, ISH data showed that HPV 16/18 DNA was uniformly located in lung tumor cells, but not in the adjacent nontumor cells. When study subjects were stratified by gender, age, and smoking status, nonsmoking female lung cancer patients who were older than 60 years old had significantly high prevalence of HPV 16/18 infection," OR 10.12 (3.88-26.38).

Prevalence of human papillomavirus (HPV) DNA in larynx and lung carcinomas. H Kaya, E Kotlioglu, S Inanli, G Ekicloglu, SU Bozkurt, A Tutkun, S Kullu. Pathologica 2001 Oct;93(5):531-534. 3/26 (11.5%) primary squamous cell lung carcinomas were positive for HPV, two for types 16/18 and one for types 6/11.

The value of HPV DNA typing in the distinction between adenocarcinomas of endocervical and endometrial origin in biopsy material. MP, BB, GS, JT, FF, DS. Pathol Int 2001 Dec;51(12):A8. 1/10 squamous cell carcinomas of the lung (10%) were positive for HPV.

HPV infections and lung cancer. KJ Syrjanen. J Clin Pathol 2002;55(12):885-891. Review. "HPV DNA has been detected in 21.7% of the 2468 bronchial carcinomas analysed to date and the same high risk types implicated in other squamous cell cancers have been identified." "The current literature now contains 2468 bronchial carcinomas subjected to HPV detection using different hybridisation methods or PCR. In total, HPV DNA has been reported in 536 (21.7%) of these cases." [If HPV is the true cause of only 20% of lung cancers, this would equal over 30,000 US cases, or ten times the number of pretended secondhand smoke deaths. Because smokers and passive smokers are more likely to have been exposed to this virus, the anti-smokers' studies, which are based on nothing but lifestyle questionnaires, automatically falsely blame the extra lung cancers cancers caused by HPV on smoking and passive smoking -cast]

The presence of human papillomavirus type 16/18 DNA in blood circulation may act as a risk marker of lung cancer in Taiwan. HL Chiou, MF Wu, YC Liaw, YW Cheng, RH Wong, CY Chen, H Lee. Cancer 2003 Mar 15;97(6):1558-1563. 149 lung cancer patients and 174 noncancer controls. "[T]he prevalence rate of HPV 16/18 in the blood circulation of lung cancer cases was significantly higher than that of noncancer controls (47.7% vs. 12.6% for HPV 16, P < 0.0001; 30.9% vs. 5.2% for HPV 18, P < 0.0001). A significantly higher HPV 16 prevalence was detected in female lung cancer patients than that of male (57.6% vs. 41.1%, P = 0.048), as well as in cases with tumor Stages III/IV than those with tumor Stages I/II (54.6% vs. 29.3%, P = 0.006). After adjusting the effects of age, gender, and smoking status, a 6.5-fold greater risk of lung cancer was demonstrated for those subjects with HPV Type 16 positive (95% CI 3.7-11.3, P < 0.0001), a 9.2-fold for HPV Type 18 positive (95% CI 4.2-20.2, P < 0.0001), and a 75.7-fold greatest risk for those with both HPV Type 16 and 18 positive (95% CI 9.8-582.1, P < 0.0001)."

Detection and typing of human papillomavirus in non-small cell lung cancer. E Zafer, MA Ergun, G Alver, FI Sahin, S Yavuzer, A Ekmekci. Respiration 2004 Jan-Feb;71(1):88-90. 2 of 40 (5%) of tumor samples collected during surgery were positive for HPV by PCR and restriction fragment length polymorphism (RFLP). Both were HPV 18.

Gender difference in human papillomarvirus infection for non-small cell lung cancer in Taiwan. YW Cheng, HL Chiou, JT Chen, MC Chou, TS Lin, WW Lai, CY Chen, YY Tsai, H Lee. Lung Cancer 2004 Nov;46(2):165-170. "HPV 6 infection was detected in 28.4% (40 of 141) lung tumors, which was significantly higher than that in non-cancer controls (1.7%, 1 of 60; P < 0.0001), however, such high prevalence was not observed for HPV 11. Among studied clinico-pathological parameters, HPV 6 infection was significantly related with gender (P = 0.002) and smoking status (P = 0.014). After being stratified by gender and smoking status, HPV 6 infection rate in lung tumors of non-smoking male patients was much higher than that in non-smoking female patients (33.3% versus 11.1%; P = 0.023), but no difference between smoking and non-smoking male patients (38.1% versus 33.3%). With adjustments for age, tumor type, and tumor stage, smoking male lung cancer patients had a much higher OR value (OR, 7.35; 95% CI, 2.11-25.58) for HPV 6 infection compared with 3.93 (95% CI, 1.17-13.12) of non-smoking male patients. Moreover, a higher prevalence of HPV 6 was detected in lung tumors of smoking male patients with early tumor stage than those with advanced stages (P = 0.008), but not in non-smoking male and female patients. A higher prevalence of HPV 6 in male lung cancer patients, as compared with female lung cancer patients, indicating not only different HPV infection routes for different genders, but also that HPV 6 infections may act as a prospective early risk marker of lung cancer for smoking male patients in Taiwan."

Frequent p16INK4a promoter hypermethylation in human papillomavirus-infected female lung cancer in Taiwan. MF Wu, YW Cheng, JC Lai, MC Hsu, JT Chen, WS Liu, MC Chiou, CY Chen, H Lee. Int J Cancer 2005 Jan 20;113(3):440-445. "p16INK4a hypermethylation frequency in non-smoking female lung tumors with HPV infection was as high as 70% (30 of 43) compared to those without HPV infection (33%; 5 of 15)."

Detection of oncogenic virus genomes and gene products in lung carcinoma. L Brouchet, S Valmary, M Dahan, A Didier, F Galateau-Salle, P Brousset, B Degano. Br J Cancer 2005 Feb 28;92(4):743-746. 122 cases of small cell lung carcinomas and non-small cell lung carcinomas for the presence of viral genomes (DNA) and/or RNA transcripts and/or proteins of human papillomaviruses (HPV) 16, 18, 31, 33, 51, Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), human cytomegalovirus (HCMV) and simian virus 40 (SV40): "None of the cases displayed a single positive tumour cell for all the viruses tested whatever the technique applied."

Infection of human papillomavirus type 18 and p53 codon 72 polymorphism in lung cancer patients from India. N Jain, V Singh, S Hedau, S Kumar, MK Daga, R Dewan, NS Murthy, SA Husain, BC Das. Chest 2005 Dec;128(6):3999-4007. 40 tumor biopsy specimens from advanced lung cancer patients; only HPV type 18 was detected in 5% (2 of 40), no other types.

Prevalence of human papillomaviruses in lung carcinomas: a study of 218 cases. CJ Coissard, G Besson, MC Polette, M Monteau, PL Birembaut, CE Clavel. Mod Pathol 2005 Dec;18(12):1606-1609. 4 out of 218 samples were positive for HPV; all were HPV 16.

Frequent FHIT gene loss of heterozygosity in human papillomavirus-infected non-smoking female lung cancer in Taiwan. J Wang, YW Cheng, DW Wu, JT Chen, CY Chen, MC Chou, H Lee. Cancer Lett 2006 Apr 8;235(1):18-25. "The fragile histidine triad (FHIT), located in chromosome region 3p14.2, had been reported to be a frequent allele with loss of heterozygosity (LOH) in smoking lung cancer and HPV-associated cervical cancer... Interestingly, a correlation between HPV 16 infection and FHIT LOH was observed in female lung cancer cases. To be more specifically, FHIT LOH frequency was remarkably increased from 18% (6 of 33) in HPV 16 non-infected female cases to 46% (11 of 24) in HPV 16 infected cases." 157 lung cancer patients total.

Human papillomavirus in lung carcinomas among three Latin American countries. A Castillo, F Aguayo, C Koriyama, K Shuyama, S Akiba, R Herrera-Goepfert, E Carrascal, G Klinge, J Sanchez, Y Eizuru. Oncol Rep 2006 Apr;15(4):883-888. In 36 lung carcinomas (14 squamous cell carcinomas, 13 adenocarcinomas, and 9 small cell carcinomas), from Colombia, Mexico and Peru, PCR using GP5+/GP6+ primers combined with Southern blot hybridization found the HPV genome in 10 (28%) of 36 cases. HPV-16 (7 cases) was the most common, followed by HPV-18 (2 cases) and HPV-33 (1 case). HPV-16 was more frequently found among female than male cases (P=0.008) but was not detected in any adenocarcinoma cases.

Different human papillomavirus 16/18 infection in Chinese non-small cell lung cancer patients living in Wuhan, China. Y Fei, J Yang, WC Hsieh, JY Wu, TC Wu, YG Goan, H Lee, YW Cheng. Jpn J Clin Oncol 2006 May;36(5):274-279. "the rates of HPV 16 and/or 18 infections in patients with lung tumors [73] were significantly higher than in 34 non-cancer control subjects (26.0 versus 2.8% for HPV 16, P = 0.030; 23.3 versus 5.7% for HPV 18, P = 0.031; 27.7 versus 5.9% for HPV 16 or 18, P = 0.003) with a similar infection frequency of HPV 16 and 18 types in lung tumors. This result indicated that HPV 16/18 infection may be associated with lung cancer development in Chinese patients from Wuhan, China. Further statistical analyses revealed that HPV 16 or 18 infection was not correlated with any clinico-pathological parameter studied, including age, gender, smoking status, tumor type, tumor stage and tumor grades. Interestingly, smoking and male patients had a higher prevalence of HPV 16, although not reaching a statistical significance, compared with non-smoking and female patients, respectively (33.3% for smokers versus 20.0% non-smokers; 33.3% for male versus 17.6% for female)." "Our recent report showed that there was an approximately 70% concordance between HPV 16 DNA detection in peripheral blood cells and lung tumor tissues of lung cancer patients. In addition, about 80% of HPV infected-female lung cancer patients from Japan and Norway had a history of cervical intraepithelial neoplasia. Moreover, our preliminary data showed an identical DNA sequence of HPV 16/18 E6, E7 and L1 in peripheral blood lymphocyte, Pap smear and lung tumor from the same lung cancer patients. These results support the possibility that HPV might have originated from the cervix and then transmitted to lung tissues through blood circulation."

The prevalence of human papillomavirus infection in Korean non-small cell lung cancer patients. MS Park, YS Chang, JH Shin, DJ Kim, KY Chung, DH Shin, JW Moon, SM Kang, CH Hahn, YS Kim, J Chang, SK Kim, SK Kim. Yonsei Med J 2007 Feb 28;48(1):69-77. In 112 patients, "The prevalence of HPV 16, 18, and 33 were 12 (10.7%), 11 (9.8%), and 37 (33.0%), respectively. Smoking status, sex, and histologic type were not statistically different in the presence of HPV DNA." Up to 60/112 (54%) were positive. 0.9% were co-infected by HPV 16 and 18, while 3.6% were co-infected by HPV 18 and 33. "HPV 33 infections had previously been considered less important than HPV 16 and 18 in lung cancer. However, our study showed a high prevalence of HPV 33 infections in Korean lung cancer patients."

Relationship between lung cancer and human papillomavirus in north of Iran, Mazandaran province. SA Nadji, T Mokhtari-Azad, M Mahmoodi, Y Yahyapour, F Naghshvar, J Torabizadeh, AA Ziaee, R Nategh. Cancer Lett 2007 Apr 8;248(1):41-6. "33 of 129 lung tumors had HPV DNA compared with 8 of 90 non-cancer control subjects (25.6% vs. 9.0%, P=0.002). The infection of HPV had an OR of 3.48 (95% CI 1.522-7.958; P=0.002). Meanwhile infection of high risk HPV types (16 and 18) had a significantly high OR of lung cancer incidence as 8.00 (95% CI 1.425-44.920; P=0.021) compared with 4.423 (95% CI 2.407-8.126; P0.0001) of smoking status."

Human papillomavirus-16 is integrated in lung carcinomas: a study in Chile. F Aguayo, A Castillo, C Koriyama, M Higashi, T Itoh, M Capetillo, K Shuyama, A Corvalan, Y Eizuru, S Akiba. Br J Cancer 2007 Jul 2;97(1):85-91. "The human papillomavirus (HPV) was detected in 20 (29%) out of 69 lung carcinomas (LCs) in Chile, by PCR and Southern blot, and was more frequently detected in squamous cell carcinoma (SQC) than in adenocarcinomas (46 vs 9%, P=0.001). HPV-16, positive in 11 cases, was the most frequently detected HPV genotype determined by DNA sequencing. HPV-16 E2/E6 ratio, estimated from real-time PCR analysis, was much lower than the unity, suggesting that at least a partial HPV-16 genome was integrated in all but one HPV-16-positive SQCs. The remaining one case was suspected to have only episomal HPV-16. Although the viral load was low in most of the LCs, a case showed the HPV-16 copy number as high as 8479 per nanogram DNA, which was even a few times higher than the minimum viral load of seven cervical carcinomas (observed viral load: 3356-609 392 per nanogram DNA)."

Human papillomavirus infections in lung cancer. Detection of E6 and E7 transcripts and review of the literature. L Giuliani, C Favalli, K Syrjanen, M Ciotti. Anticancer Res 2007 Jul-Aug;27(4C):2697-704. Brief review and new data of the authors on detection of E6 and E7 transcripts in lung cancer samples. "[D]uring the integration of the virus into the host cell genome, part of the L1 gene may be lost as well as the E2 gene and the consensus primers MY09/MY11, frequently used to screen these biopsies could then be inadequate for amplification." Transcription of E6 and E7 was observed in fresh lung tumor samples, as in cervical cancers.

Detection of oncogenic viruses SV40, BKV, JCV, HCMV, HPV and p53 codon 72 polymorphism in lung carcinoma. L Giuliani, T Jaxmar, C Casadio, M Gariglio, A Manna, D D'Antonio, K Syrjanen, C Favalli, M Ciotti. Lung Cancer 2007 Sep;57(3):273-281. 78 tumors. "11 (14.1%) were positive for T-Ag gene of SV40, while BKV and JCV sequences were both amplified in 1 tumor only. Altogether, 10/78 lesions were HPV-positive; six HPV16, one HPV31, two HPV6/53 and one HPV16/18. All HPV DNA-positive samples except one also expressed E6 and E7 transcripts. HCMV was amplified in 18 (23%) cases." Co-detection of SV40 and HCMV was statistically significant (OR=5.500, 95%CI 1.43-21.02; p=0.015).

The American Cancer Society's propaganda circus: Dr.Arash Rezazadeh and colleagues from the University of Louisville, Kentucky, USA. Abstract No. 124PD; Friday 25th April, 09:50, presented at the 1st European Lung Cancer Conference, jointly organized by the European Society for Medical Oncology (ESMO) and the International Association for the Study of Lung Cancer (IASLC) in Geneva, Switzerland. Six of 23 lung cancers, all from smokers, were positive for HPV, one of which was a metastasized cervical cancer. Of the remaining 5 virus-positive samples, two were HPV type 16, two were HPV type 11 and one was HPV type 22. An accompanying study found measles virus in more than half of 65 non-small cell lung cancers. Both studies are to be published in the Journal of Thoracic Oncology, www.jto.org. This is the first known mention of HPV involvement in lung cancer in the U.S. mass media. The story was spin-doctored by the American Cancer Society, because the media are nothing but their corrupt lie-spewing puppets who would never dream of uttering a peep without the approval of their masters. CBS News posted a WebMD article on April 23, 2008, whose lead sentence was nothing but the American Cancer Society's stock anti-smoking propaganda, which was likewise parroted by all the rest. "Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, described both research efforts as 'interesting.' But he cautioned that more research needs to be done on each front... 'But I think the HPV study is the more interesting of the two,' Lichtenfeld added, 'since HPV is obviously already implicated in other cancers. But this is a small study, and it only suggests a possible link to lung cancer without answering a lot of questions. I would like to know, for example, whether patients who are not smokers but who develop lung cancer have a higher rate of HPV. But for now, I would not yet conclude that HPV increases risk, nor would I tie the HPV vaccine to any risk.'" And what about those 50-plus other studies which preceded it, several of which did include non-smokers? The Cancer Society didn't bother to wait for 50 studies before proclaiming its absolute certainty that secondhand smoke causes lung cancer! (Possible Viral Links to Lung Cancer Risk Uncovered. By Alan Mozes. U.S. News and World Report, April 25, 2008.) "'We think HPV has a role as a co-carcinogen which increases the risk of cancer in a smoking population,' Rezazadeh said in a statement." This deceitful statement also ignores the studies showing that HPV also has a major role in non-smokers' lung cancer. "Though the study is the first to note the combined effects of smoking and HPV on the lungs, doctors have known for a while that women who smoke and contract HPV are more likely to develop cervical cancer than nonsmokers, said Dr. Lauren F. Streicher, an OB/GYN and professor at Northwestern Medical School." This is a lie, because this study only evaluated the rate of HPV infection in lung cancers from smokers and there was no comparison group of any kind. "'Smoking plays a key role in the rate of conversion to malignancy in cervical cancer too,' she said. 'Seventy to 80 percent of women are exposed to HPV, but less than 1 percent of women get cervical cancer. We know lesions on the cervix are more likely to become cancerous in smokers.'" This is a lie, too. The American Cancer Society and its lackeys deliberately use defective studies in order to falsely blame smoking for cervical cancer. For example, they only look at one strain of HPV, while ignoring the others that are also known to cause cervical cancer, and also the fact that infection by multiple strains is more likely to result in cancer than infection by a single strain; and they ignore differences in the amount of exposure to the infection, all so that they can purposely exploit the socioeconomic differences between smokers and nonsmokers to manufacture their fraudulent claim that smoking causes cervical cancer! And the filth in the media eagerly spew their lies, and embrace their scientific fraud, and refuse to allow any criticism. (Study Links HPV to Lung Cancer. By Russell Goldman. ABC News, Apr. 28, 2008.) (Rezazadeh 2008 / ESMO link died http://www.esmo.org/news/?news_id=219.)

Human papillomavirus type 16 and 18 infection is associated with lung cancer patients from the central part of China. Y Wang, A Wang, R Jiang, H Pan, B Huang, Y Lu, C Wu. Oncol Rep 2008 Aug;20(2):333-239. In 313 fresh lung tumor specimens tested for HPV with polymerase chain reaction and non-isotopic in situ hybridization, "44.1% of (138/313) non-small cell lung carcinoma (NSCLC) samples were positive for HPV detection, while 4.2% (4/96) of lung benign controls were positive for HPV 16 and 18 DNA. HPV infection was significant between lung squamous cell carcinoma and adenocarcinoma as well as smoking and non-smoking patients. In HPV-positive lung cancer tissues, abnormal p53 protein accumulation was seen in 97 of the 138 carcinomas (70.3%) and expression of pRb in 54 of the 138 carcinomas (39.1%). There was an obvious relationship between the presence of papilloma viral DNA and abnormal p53 protein accumulation and pRb depletion. Cell proliferation and apoptosis were correlated with HPV infection in NSCLC samples."

Association between expression of human papillomavirus 16/18 E6 oncoprotein and survival in patients with stage I non-small cell lung cancer. NY Hsu, YW Cheng, IP Chan, HC Ho, CY Chen, CP Hsu, MH Lin, MC Chou. Oncol Rep 2009 Jan;21(1):81-87. 217 patients with stage I NSCLC. "HPV-16 E6 oncoprotein was expressed in 49 (22.6%) patients and HPV-18 E6 oncoprotein was expressed in 31 (14.3%) patients. Statistical analysis revealed that the prevalence of expression of HPV-16 and HPV-18 E6 oncoproteins was significantly high in female patients, nonsmokers and patients with adenocarcinoma. The adjusted odds ratio for expression of HPV-16 E6 oncoprotein in female patients was 2.275 [95% confidence interval (CI), 0.999-5.179] and that in patients with adenocarcinoma was 2.320 (95% CI, 1.029-5.232)."

Assessment of human papillomavirus and Epstein-Barr virus in lung adenocarcinoma. WT Lim, KL Chuah, SS Leong, EH Tan, CK Toh. Oncol Rep 2009 Apr;21(4):971-975. 110 patients with adenocarcinoma of the lung from a single institution database of lung cancer, 65 male and 45 female, by "an in situ hybridization method that probed for high-risk and low-risk HPV and EBV... There were similar number of smokers and non-smokers. Across all stages HPV and EBV staining was absent from all tissues examined."

Correlation of HPV-16/18 infection of human papillomavirus with lung squamous cell carcinomas in Western China. Y Yu, A Yang, S Hu, H Yan. Oncol Rep 2009 Jun;21(6):1627-1632. "72 lung squamous cell carcinomas, 37 lung adenocarcinomas and 71 non-cancer controls, were analyzed by INNO-LIPA Genotype polymerase chain reaction (PCR) and real-time PCR analysis. The data showed that 51.4% (37/72) of lung squamous cell carcinoma samples, 16.2% (6/37) of adenocarcinoma, and 22.5% (16/71) of non-cancer controls were HPV DNA positive. The risk of lung squamous cell carcinomas was 3.5 times higher among people HPV-positive (odds ratio 3.5, 95% CI 1.6-7.3, p<0.001) compared with the HPV- negative population. Adjusted by smoking status, the risk of lung squamous cell carcinomas was 3.5 times higher among people HPV-positive (odds ratio 3.5, 95% CI 1.7-7.5, p=0.001) compared with the HPV-negative population. The risk of lung squamous cell carcinomas was 16.9 times higher for patients with positive HPV-16 (odds ratio 16.9, 95% CI 3.8-75.3, p<0.0001) than negative HPV-16. Adjusted by smoking status, the risk of lung squamous cell carcinomas was 17.4 times higher among people HPV-16 positive (odds ratio 17.4, 95% CI 3.9-77.5, p<0.0001) compared with HPV-16 negative people."

REVIEW: Incidence of human papilloma virus in lung cancer. F Klein, WF Amin Kotb, I Petersen. Lung Cancer 2009 Jul;65(1):13-18. "53 publications reporting on 4508 cases were reviewed and assessed for the following parameters: continent and region of the study, number of cases, detection method, material type, HPV type, histological subtype and number of the HPV-positive cases. Overall, the mean incidence of HPV in lung cancer was 24.5%. While in Europe and the America the average reported frequencies were 17% and 15%, respectively, the mean number of HPV in asian lung cancer samples was 35.7%. There was a considerable heterogeneity between certain countries and regions. Particular high frequencies of up to 80% were seen in Okinawa (Japan) and Taichung (Taiwan). However, there were also discrepant results within the same region pointing to methodological differences and the need for validation. All lung cancer subtypes were affected and especially the high risk types 16, 18, 31 and 33 as well as the low risk types 6 and 11 were found, the later mainly in association with squamous cell carcinomas. The data suggest that HPV is the second most important cause of lung cancer after cigarette smoking and strongly argues for additional research on this issue."

[The Relationship between the Status of Human Papillomavirus 16/18 Infection and the Expression of Bcl-2 and Bax in Squamous Cell Carcinomas of the Lung.] Y Xu, B Cheng, H Pan, A Wu, L Zhang. Zhongguo Fei Ai Za Zhi 2009 Aug 20;12(8):849-852. "Of 44 patients with squamous cell carcinomas of the lung, 12 (27.27%) were found to be HPV negative. Twenty-three (52.27%) were found to be integrated form HPV, 9 (20.45%) were found to be large number of episomal form and a few integrated form HPV. And no simplex episomal form HPV was found. HPV 16/18 DNA could not be detected in 15 non-carcinomas tissues. A significantly higher 16/18 DNA positive rates in carcinomas tissues compared to non-carcinomas tissues (P<0.001)."

Detection of human papillomaviruses type 16, 18 and 33 in bronchial aspirates of lung carcinoma patients by polymerase chain reaction: a study of 84 cases in Croatia. BV Branica, S Smojver-Jezek, Z Juros, S Grgić, N Srpak, D Mitrecić, S Gajović. Coll Antropol 2010 Mar;34(1):159-162. 3 of 84 [3.6%] lung carcinomas were positve for HPV types 16, 18, or 33.

Prevalence of human papillomavirus 16/18/33 infection and p53 mutation in lung adenocarcinoma. R Iwakawa, T Kohno, M Enari, T Kiyono, J Yokota. Cancer Sci 2010 Aug 1;101(8):1891-1896. "[N]one of the 297 lung AdCs showed positive signals for HPV 16/18/33 DNA, indicating that HPV-DNA is not or is very rarely integrated in lung AdC genomes in the Japanese. Furthermore, none of the lung AdCs showed positive signals by nested PCR with HPV 16/18 type-specific primers." HPV 16/18/33 DNA was also not found in 91 lung cancer cell lines, 30 from Japan and 61 from the U.S. They claim that "These results indicate that HPV 16/18/33 infection does not play a major role in the development of lung AdC in Japan nor in the USA."

Frequent presence of incomplete HPV16 E7 ORFs in lung carcinomas: Memories of viral infection. D Krikelis, G Tzimagiorgis, E Georgiou, C Destouni, T Agorastos, C Haitoglou, S Kouidou. J Clin Virol 2010 Nov;49(3):169-174. 29 lung carcinoma specimens, 16 non-cancerous lung tissue specimens from the same patients and 31 bronchial washings from different lung cancer patients. "Amplification of the entire HPV16 E7 ORF, using two protocols, demonstrated the absence of the specific HPV16 E7 sequences (74 samples either tested negative by the first PCR protocol or false positive by the second, based on sequencing or AvaII or PvuII digestion). However, both schemes targeting smaller E7 segments revealed the frequent presence of HPV16 E7 sequences in lung carcinoma specimens (14/23 [61%] positive by either scheme)... Restriction endonuclease analysis is critical for verifying the reliability of the detection of these sequences."

Human papillomavirus-16 presence and physical status in lung carcinomas from Asia. F Aguayo, M Anwar, C Koriyama, A Castillo,Q Sun, J Morewaya, Y Eizuru, S Akiba. Infect Agent Cancer 2010 Nov 16;5:20. "HPV-16 was present in 8/59 (13%) samples. According to histological type, HPV-16 was detected in 8/18 (44%) squamous cell carcinomas (SQCs), which were mainly from Pakistan; 0/38 (0%) adenocarcinomas (ACs), which were mainly from China; and in 0/4 (0%) small cell carcinomas (SCLCs)." Viral load ranged from 411 to 2345 copies/100 ng of genomic DNA. "HPV-16 genome was found integrated into the host genome in every HPV-16 positive carcinoma." "The HPV integration frequently disrupts E2 ORF causing E6 and E7 overexpression because E2 protein functions as a repressor of p97 promoter in HPV-16. The E6 and E7 overexpression induce p53 and pRb loss, respectively."

Frequent presence of incomplete HPV16 E7 ORFs in lung carcinomas: memories of viral infection. D Krikelis, G Tzimagiorgis, E Georgiou, C Destouni, T Agorastos, C Haitoglou, S Kouidou. J Clin Virol 2010 Nov;49(3):169-174. 29 lung carcinoma specimens, 16 non-cancerous lung tissue specimens from the same patients and 31 bronchial washings from different lung cancer patients. "Amplification of the entire HPV16 E7 ORF, using two protocols, demonstrated the absence of the specific HPV16 E7 sequences... However, both schemes targeting smaller E7 segments revealed the frequent presence of HPV16 E7 sequences in lung carcinoma specimens (14/23 positive by either scheme)."

Human papillomavirus (HPV) and Merkel cell polyomavirus (MCPyV) in non small cell lung cancer. J Joh, AB Jenson, GD Moore, A Rezazedeh, SP Slone, SJ Ghim, GH Kloecker. Exp Mol Pathol 2010 Dec;89(3):222-226. "HPVs were only detected in 5 adenocarcinomas (16.7% of all lung cancers examined). Three were positive for HPV-16, 1 for HPV-11 and 1 had an unknown HPV type DNA. None was identified in benign tissue. MCPyV DNA was detected in 5 NSCLCs (16.7%). Three of the 5 were identified in squamous carcinomas, 1 in adenocarcinoma, and 1 in an unspecified NSCLC. Two additional samples were positive for MCPyV DNA within benign adjacent lung tissue only. In one adenocarcinoma, HPV-11 was identified in an adenocarcinoma, and MCPyV DNA was detected in the adjacent "benign" tissue. HPV and MCPyV were directly associated with 33.3% of NSCLC."

The Empire Strikes Back - Assessment of Human Papillomavirus in Lung Tumor Tissue. J Koshiol, M Rotunno, ML Gillison, LJ Van Doorn, AK Chaturvedi, L Tarantini, H Song, WG Quint, L Struijk, AM Goldstein, A Hildesheim, PR Taylor, S Wacholder, PA Bertazzi, MT Landi, NE Caporaso. J Natl Cancer Inst 2011 Mar 16;103(6):501-507. 246 adenocarcinomas and 137 squamous cell carcinomas. Predictably, the National Cancer Institute couldn't find any HPV of any type in any of the samples. Although they admit that other types of HPV are found in the lung, they would have us believe that HPV plays no role in lung cancer in Western populations, and insinuate that others' results were due to contamination. This is the same story the health establishment told about EBV and nasopharyngeal carcinoma. Caporaso also happens to be the author of a study claiming that passive smoking during childhood increases the risk of lung cancer in never smokers. The National Cancer Institute has problems that can't be fixed by washing the labware, but as long as the river of research can flow around their rock of dogmatism, the truth will come out.

COMMENT: We can expect the apparent incidence of HPV in lung cancer to increase, because not all studies looked for all the types of HPV implicated, and because of improvements in methodology. The issue which most urgently needs to be addressed is that studies which are based on nothing but lifestyle questionnaires exploit different rates of HPV exposure between smokers, passive smokers, and non-passive smoke-exposed non-smokers to falsely blame smoking and passive smoking for lung cancer that is actually caused by HPV. Furthermore, it is necessary to address the fact that the American Cancer Society and its clones have deliberately and systematically used defective studies of this type in order to push their political agenda of outlawing tobacco - an agenda which the politically-connected elite at Harvard and Yale have been pursuing since the days of Rev. George Trask.

Human papillomavirus infection in lung and esophageal cancers: Analysis of 485 Asian cases. A Goto, CP Li, S Ota, T Niki, Y Ohtsuki, S Kitajima, S Yonezawa, C Koriyama, S Akiba, H Uchima, YM Lin, KT Yeh, JS Koh, CW Kim, KY Kwon, ME Nga, M Fukayama. J Med Virol 2011 Aug;83(8):1383-1390. 6.3% of lung squamous cell carcinomas and 7% of lung adenocarcinoma from Japan, Korea, Singapore and Taiwan were positive for HPV by PCR and ISH. Most were HPV types 16/18.

HPV in exhaled breath condensate of lung cancer patients. GE Carpagnano, A Koutelou, MI Natalicchio, D Martinelli, C Ruggieri, A Di Taranto, R Antonetti, F Carpagnano, MP Foschino-Barbaro. Br J Cancer 2011 Oct 11;105(8):1183-1190. 16.4% of 89 patients and none of 68 controls were positive for HPV in exhaled breath condensate, paired bronchial brushing and neoplastic lung tissue.

HPV analysis in distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma. JA Bishop, T Ogawa, X Chang, PB Illei, E Gabrielson, SI Pai, WH Westra. Am J Surg Pathol 2012 Jan;36(1):142-148. From Johns Hopkins. 54 SCCs from patients with a previous head and neck SCC, and 166 primary lung carcinomas. 11 / 220 (5%) were HPV-positive, and all were from patients with prior head and neck cancers. Time since treatment of head and neck cancer ranged from 1 to 97 months.

Detection of human papillomavirus genotypes in bronchial cancer using sensitive multimetrix assay. K Syrjänen, M Silvoniemi, E Salminen, T Vasankari, S Syrjänen. Anticancer Res 2012 Feb;32(2):625-631. 4 / 77 (5.2%) patients diagnosed and treated for lung cancer during 2008-2010 were positive for HPV. 24 low- and high-risk types tested for; three were HPV16 and one HPV6 and HPV16. Three had quit smoking for more than 22 years.

Human Papillomavirus DNA and p16 Gene in Squamous Cell Lung Carcinoma. LB Gatta, P Balzarini, A Tironi, A Berenzi, A Benetti, F Angiero, P Grigolato, E Dessy. Anticancer Res 2012 Aug;32(8):3085-3089. 50 cases. "HPV DNA was found in two out of 50 cases (4%, p>0.05). In five cases, p16 protein expression was positive. The data showed that in 45/50 cases (90%, p<0.05) HPV DNA and p16 were both negative, in 2/50 cases (4%) both were positive, and in 3/50 (6%) cases, HPV DNA was negative and p16 positive. FISH analysis for p16 gene showed aneusomia of chromosome 9 with or without loss of p16 gene in all cases (100%, p<0.05)."

LATEST REVIEW: Detection of Human Papillomavirus in Lung Cancer: Systematic Review and Meta-analysis. K Syrjänen. Anticancer Res 2012 Aug;32(8):3235-3250. "One hundred studies were eligible, covering 7,381 lung cancer cases from different geographical regions. Altogether, 1,653 (22.4%) samples tested HPV-positive; effect size was 0.348 (95% CI=0.333-0.363; fixed-effects model), and 0.220 (95% CI=0.18-0.259; random effects model)... These meta-analytic results imply that the reported variability in HPV detection rates in lung cancer is better explained by geographical study origin and histological types of cancer than by the HPV detection method itself. In formal meta-regression, however, none of these three factors were significant study-level co-variates accounting for the heterogeneity of the summary effect size estimates, i.e. HPV prevalence in lung cancer."

EGFR mutations and human papillomavirus in lung cancer. T Kato, C Koriyama, N Khan, T Samukawa, M Yanagi, T Hamada, N Yokomakura, T Otsuka, H Inoue, M Sato, S Natsugoe, S Akiba. Lung Cancer 2012 Nov;78(2):144-147. "Thirteen (31%) out of 42 cases had EGFR mutations. Although these mutations were tended to be observed in females, non-smokers, or adenocarcinomas, there was no statistically significant associations. HPV DNA was found in 7/42 (17%) lung tumors. The frequency of HPV presence did not differ in histological types. The presence of HPV DNA was significantly related to EGFR mutations (P=0.021), especially in adenocarcinomas of the lung (P=0.014). HPV-positive lung tumors accounted for 38% and 7% of those with and without EGFR mutations, respectively."

Testing of human papillomavirus in lung cancer and non-tumor lung tissue. A Galvan, S Noci, F Taverna, C Lombardo, S Franceschi, U Pastorino, TA Dragani. BMC Cancer 2012 Nov 12;12(1):512. 100 lung cancer patients from Italy and the UK. "No HPV was detected in tumor specimens nor in normal lung tissue of any patient."

Human Papillomavirus in Non-Small-Cell Lung Cancer: The Impact of EGFR Mutations and the Response to Erlotinib. D Márquez-Medina, A Gasol-Cudós, MT Taberner-Bonastre, JC Samamé Pérez-Vargas, A Salud-Salvia, A Llombart-Cussac. Arch Bronconeumol 2013 Feb;49(2):79-81. 2.5% of 40 non-small-cell lung cancers were positive for HPV, type[s] not specified.

Human papilloma virus genome is rare in North American non-small cell lung carcinoma patients. N Yanagawa, A Wang, D Kohler, C Santos Gda, J Sykes, J Xu, M Pintilie, MS Tsao. Lung Cancer 2013 Mar;79(3):215-220. 204 adenocarcinomas and 132 squamous cell carcinomas. "HPV genome was detected in 5 (1.5%) of 336 tumors studied by both ISH and PCR; all of them were typed as HPV16 and found in SqCC (3.8%). Despite being solitary tumors and clinically considered as primary lung cancers, all 5 patients had past history of HPV associated squamous cell carcinomas of other organ sites, thus highly suggestive of being metastases. P16 immunostaining was found in 137 (40.8%) tumors, with 109 (32.4%) showing high level expression. All HPV positive (+) cases showed P16 high expression."

High-Risk Human Papillomavirus-Positive Lung Cancer: Molecular Evidence for a Pattern of Pulmonary Metastasis. RA van Boerdonk, JM Daniels, E Bloemena, O Krijgsman, RD Steenbergen, RH Brakenhoff, K Grünberg, B Ylstra, CJ Meijer, EF Smit, PJ Snijders, DA Heideman. J Thorac Oncol 2013 Apr 8 [Epub ahead of print]. "Whereas all primary lung carcinomas were hrHPV-negative (211 of 211, 100%), three hrHPV-positive equivocal carcinomas (3 of 12, 25%) were identified. These patients (1 male, 2 females) had a history of hrHPV-associated disease; one tonsillar and two cervical carcinomas. A clonal relationship between individual tumor pairs was supported by identical hrHPV genotype, pattern of p16 expression, HPVE7 mRNA expression, and genomic aberrations. CONCLUSIONS:: hrHPV presence in a tumor with primary presentation in the lungs signifies pulmonary metastasis from a primary hrHPV-positive cancer elsewhere in the body. No support was found for an attribution of hrHPV infection to the development of primary LC."

Mechanisms

The pivotal role of phosphatidylinositol 3-kinase–Akt signal transduction in virus survival. S Cooray. J Gen Virol 2004;85:1065-1076. A number of viruses including EBV, HPV, HBV and HCV have the ability to establish long-term infections in the host, either through the establishment of latent or chronic infections, which can ultimately lead to cellular transformation. It appears that the gene products of these viruses stimulate PI3K–Akt-mediated cell survival and thereby block apoptosis of the cells they infect. This contributes to both virus survival and oncogenic transformation (Fig. 2, Table 1). However, activation of this pathway is not only required for viral transformation but also for other stages of the virus life cycle. EBV BZLF1-mediated reactivation from latency, for example, requires the activation of PI3K and Akt. Productive polyomavirus infection requires the up-regulation of PI3K–Akt cell survival and cellular proliferation."

An association of DNMT3b protein expression with P16INK4a promoter hypermethylation in non-smoking female lung cancer with human papillomavirus infection. TS Lin, H Lee, RA Chen, ML Ho, CY Lin, YH Chen, YY Tsai, MC Chou, YW Cheng. Cancer Lett 2005 Aug 8;226(1):77-84. "Interestingly, DNMT3b protein expression was significantly correlated with p16INK4a promoter hypermethylation (P=0.023) and HPV 16/18 infections (P<0.001), respectively. Moreover, the correlation between p16INK4a promoter hypermethylation and DNMT3b protein expression was exclusively seen in female cases (P=0.035)."

Human papillomavirus 16/18 E6 oncoprotein is expressed in lung cancer and related with p53 inactivation. YW Cheng, MF Wu, J Wang, KT Yeh, YG Goan, HL Chiou, CY Chen, H Lee. Cancer Res 2007 Nov 15;67(22):10686-10693. 122 lung tumors. "Western blotting showed that E6 protein was indeed expressed in HPV16-infected cells and a lower level of p53 protein was observed in E6-positive cells compared with E6-negative cells. Moreover, the levels of p21(WAF1/CIP1) and mdm2 mRNA in E6-positive cells were lower than in E6-negative cells. The interaction of E6 with p53 protein was revealed by immunoprecipitation assay showing that p53 could be inactivated by E6 protein. Conversely, p53 proteins and p21(WAF1/CIP1) and mdm2 mRNA expressions were restored in E6-knockdown cells by RNA interference compared with control cells. These results reveal that HPV16/18 E6 may be partially involved in p53 inactivation to down-regulate p21(WAF1/CIP1) and mdm2 transcription. In conclusion, HPV16/18 E6 is indeed expressed in HPV DNA-positive lung tumors and is involved in p53 inactivation to contributing to HPV-mediated lung tumorigenesis."

Human papillomavirus type 16/18 up-regulates the expression of interleukin-6 and antiapoptotic Mcl-1 in non-small cell lung cancer. YW Cheng, H Lee, MY Shiau, TC Wu, TT Huang, YH Chang. Clin Cancer Res 2008 Aug 1;14(15):4705-4712. "Human papillomavirus (HPV) 16/18 infection is reported to be associated with nonsmoking Taiwanese female lung cancer. In this study, we attempted to further reveal the association between HPV infection with Mcl-1 and interleukin (IL)-6 expressions and to elucidate the roles of HPV infection in lung tumorigenesis... Lung tumors (70.9% and 57.0%) had positive IL-6 and Mcl-1 immunostainings, respectively. Significant correlation between IL-6 and Mcl-1 expression were observed (P < 0.0001). Both IL-6 and Mcl-1 expression were significantly associated with HPV 16/18 infection (P = 0.014 and P = 0.004, respectively). IL-6 and Mcl-1 protein levels were not only elevated in HPV 16/18 E6- and E7-transfected A549 cells but also in TL-1 cells."

Human telomerase reverse transcriptase activated by E6 oncoprotein is required for human papillomavirus-16/18-infected lung tumorigenesis. YW Cheng, TC Wu, CY Chen, MC Chou, JL Ko, H Lee. Clin Cancer Res 2008 Nov 15;14(22):7173-7179. In 135 lung tumors, "hTERT mRNA levels in E6-positive tumors, which were prevalent in females, nonsmokers, and adenocarcinomas, were significantly higher than in E6-negative tumors. In addition, hTERT mRNA levels in early tumors (stage I) were greater than levels in advanced tumors (stages II and III). Chromatin immunoprecipitation assay showed that Sp1 cooperated with c-Myc to activate hTERT transcription in TL-1 cells, which was similar to the SiHa cells. The telomerase activity of the TL-1 cells decreased concomitantly with the transfection of various doses of E6- or hTERT-RNAi. A soft-agar assay showed that the oncogenic potential of TL-1 cells was significantly reduced after being transfected with E6-RNAi. Moreover, a colony of TL-1 cells could not form after transfection with hTERT-RNAi."

HPV E6 protein interacts physically and functionally with the cellular telomerase complex. X Liu, A Dakic, Y Zhang, Y Dai, R Chen, R Schlegel. Proc Natl Acad Sci USA 2009 Nov 3;106(44):18780-18785. "Discussion... The observation that E6 mediates telomerase activation via two separate but related pathways suggests that telomerase is a critical target for HPV. However, it seems unlikely that the primary intent of increasing hTERT protein and telomerase activity is to immortalize cells and facilitate oncogenic conversion, since tumorigenic cells are nonpermissive for HPV replication. Rather, since hTERT expression is a feature of stem cells, it is possible that E6 mediates the conversion of keratinocytes into a stem-like phenotype such that it can facilitate HPV persistence (or latency) in squamous epithelium."

Integrative Genomic Analyses Identify BRF2 as a Novel Lineage-Specific Oncogene in Lung Squamous Cell Carcinoma. WW Lockwood, R Chari, BP Coe, KL Thu, C Garnis, CA Malloff, J Campbell, AC Williams, D Hwang, C-Q Zhu, TPH Buys, J Yee, JC English, C MacAulay, M-S Tsao, AF Gazdar, JD Minna, S Lam, WL Lam. PLoS Medicine 2010 Jul;7(7):e1000315. >330 clinical tumor samples. "[F]ocal regions of Chromosome 8p are amplified in about 40% of lung SqCCs, but... DNA loss in this region is the most common alteration in lung adenocarcinomas... Artificially induced expression of BRF2 in bronchial epithelial cells made these normal cells behave like tumor cells, whereas reduction of BRF2 expression in squamous carcinoma cells made them behave more like normal bronchial epithelial cells. Finally, BRF2 was frequently activated in two early stages of squamous cell carcinoma—bronchial carcinoma in situ and dysplastic lesions." "Frequent activation of BRF2 in >35% preinvasive bronchial carcinoma in situ, as well as in dysplastic lesions, provides evidence that BRF2 expression is an early event in cancer development of this cell lineage."

Up-regulation of interleukin-17 expression by human papillomavirus type 16 E6 in nonsmall cell lung cancer. YH Chang, CW Yu, LC Lai, CH Tsao, KT Ho, SC Yang, H Lee, YW Cheng, TC Wu, MY Shiau. Cancer 2010 Oct 15;116(20):4800-4809. 79 NSCLC tumor tissues. "Immunohistochemical data showed that 48.1% of lung tumors had IL-17 staining, which was significantly associated with patients' sex (P = .03), HPV infection (P = .002), and tumor stage (P = .03). Significant correlations of IL-17 with IL-6 (P < .001) and IL-17 with Mcl-1 (P < .001) expression were also observed." Cell growth rate was increased in a human NSCLC cell line.

cIAP2 upregulated by E6 oncoprotein via epidermal growth factor receptor/phosphatidylinositol 3-kinase/AKT pathway confers resistance to cisplatin in human papillomavirus 16/18-infected lung cancer. HH Wu, JY Wu, YW Cheng, CY Chen, MC Lee, YG Goan, H Lee. Clin Cancer Res 2010 Nov 1;16(21):5200-5210. "Among the tumor groups, cIAP2 expression correlated significantly with HPV16/18 E6, EGFR, and p-AKT. We followed up 46 of 136 patients who had tumor recurrence and/or metastasis and underwent chemotherapy. Tumors with cIAP2-positive immunostaining were associated with a poorer tumor response to chemotherapy compared with those with negative immunostaining. CONCLUSIONS: cIAP2 upregulated by E6 via EGFR/PI3K/AKT cascades may contribute to cisplatin resistance, revealing that the EGFR or PI3K inhibitor combined with cisplatin may improve the chemotherapeutic efficacy in HPV-infected lung cancer."

Overexpression of human papillomavirus (HPV) type 16 oncoproteins promotes angiogenesis via enhancing HIF-1α and VEGF expression in non-small cell lung cancer cells. G Li, L He, E Zhang, J Shi, Q Zhang, AD Le, K Zhou, X Tang. Cancer Lett 2011 Dec 8;311(2):160-170. "[O]verexpression of HPV-16 E6 and E7 oncoproteins in NSCLC cells significantly promoted angiogenesis both in vitro and in vivo, and correspondingly, an enhanced expression of HIF-1α and VEGF, important pro-angiogenic factors in tumor angiogenesis. Meanwhile, overexpression of HPV-16 oncoproteins also led to HIF-1α-dependent increases in the secretion of several other pro-angiogenic factors, including IL-8."

A Possible Role for Polyomaviruses

Detection of SV40-like DNA sequences in pleural mesothelioma, bronchopulmonary carcinoma and other pulmonary diseases. F Galateau-Salle, P Bidet, Y Iwatsubo, E Gennetay, A Renier, M Letourneux, JC Pairon, S Moritz, P Brochard, MC Jaurand, F Freymuth. Dev Biol Stand 1998;94:147-152. 15 mesotheliomas, 63 additional bronchopulmonary carcinomas, one parietal osteosarcoma and non-malignant lung samples, and 8 from organizing pleuritis. "47.6% of mesotheliomas, 28.6% of primary bronchopulmonary carcinomas and 16% of non-neoplasic lung diseases contained SV40-like DNA sequences. No statistically significant difference in the occurrence of these DNA sequences was found between malignant mesothelioma and bronchopulmonary carcinoma. However, a significantly higher number of mesothelioma cases exhibited SV40- like DNA sequences in comparison with non-malignant pleural and pulmonary tissues. The DNA sequences were not related to BK and JC virus sequences."

Identification of a novel polyomavirus from patients with acute respiratory tract infections. AM Gaynor, MD Nissen, DM Whiley, IM Mackay, SB Lambert, G Wu, DC Brennan, GA Storch, TP Sloots, D Wan. PLoS Pathog 2007;3(5): e64. The virus was found in 43 / 2,135 patients with acute respiratory disease, including pneumonia. 86% were under 3 years old. "Much of the interest in polyomaviruses and SV40 in particular derives from the transforming properties carried by the early transcriptional region of the viral genome that encodes for the small T antigen (STAg) and and large T antigen (LTAg). T antigen is capable of binding both p53 and Rb proteins and interfering with their tumor suppressor functions. The early region alone is sufficient to transform established primary rodent cell lines and in concert with telomerase and ras transforms primary human cells... Since the T antigen of WU is predicted to have transforming properties by analogy to other polyomavirus T antigens, one question currently under investigation is whether a subset of human tumors may be associated with WU."

Identification of a third human polyomavirus. T Allander, K Andreasson, S Gupta, A Bjerkner, G Bogdanovic, MA Persson, T Dalianis, T Ramqvist, B Andersson. J Virol 2007 Apr;81(8):4130-4136. " The virus was found by PCR in 6 (1%) of 637 nasopharyngeal aspirates and in 1 (0.5%) of 192 fecal samples but was not detected in sets of urine and blood samples. Since polyomaviruses have oncogenic potential and may produce severe disease in immunosuppressed individuals, continued searching for the virus in different medical contexts is important." "There are putative binding sites for p53, as well as the Rb family of tumor suppressor proteins, in the LT antigen of KIPyV, which indicates that a role for this virus in tumorigenesis cannot be excluded."

JC [corrected] virus detection in human tissue specimens. H Zheng, Y Murai, M Hong, Y Nakanishi, K Nomoto, S Masuda, K Tsuneyama, Y Takano. J Clin Pathol 2007 Jul;60(7):787-793. "The positive rate of JCV was high in lung carcinoma, compared with normal lung tissue (p<0.05)." [Details in full article.] 50 lung cancers, 20 normal lung tissue, in paraffin, by multiple methods. Table 1 Jamestown Canyon virus (JCV) existence in lung samples by nested PCR followed by Southern blot targeting T-antigen: 29/50 (58%) lung carcinomas were positive for T-antigen of JCV, versus 2/20 (10%) normal lung tissue samples, p<0.001.

Oncogenic role of JC virus in lung cancer. H Zheng, HO Abdel Aziz, Y Nakanishi, S Masuda, H Saito, K Tsuneyama, Y Takano. J Pathol 2007 Jul;212(3):306-315. 103 lung carcinomas vs. 18 normal lung tissues. "Normal lung tissue was positive significantly less frequently, and contained a lower copy number of JCV than lung carcinomas (p<0.05), and copies were lower in lung adenocarcinomas than in squamous, small or large cell carcinomas (p<0.05). In situ PCR and immunolabelling revealed JCV positivity in the nuclei of lung carcinoma cells. The JCV copy number correlated closely with sex, and expression of Ki-67 and membrane beta-catenin (p<0.05), but not with age, tumour size, pleural invasion, lymph node metastasis, expression of caspase-3, cytoplasmic beta-catenin, p53 or Rb, prognosis, smoking or cancer family history (p>0.05)."

Detection of oncogenic viruses SV40, BKV, JCV, HCMV, HPV and p53 codon 72 polymorphism in lung carcinoma. L Giuliani, T Jaxmar, C Casadio, M Gariglio, A Manna, D D'Antonio, K Syrjanen, C Favalli, M Ciotti. Lung Cancer 2007 Sep;57(3):273-281. 78 tumors. "11 (14.1%) were positive for T-Ag gene of SV40, while BKV and JCV sequences were both amplified in 1 tumor only. Altogether, 10/78 lesions were HPV-positive; six HPV16, one HPV31, two HPV6/53 and one HPV16/18. All HPV DNA-positive samples except one also expressed E6 and E7 transcripts. HCMV was amplified in 18 (23%) cases." Co-detection of SV40 and HCMV was statistically significant (OR=5.500, 95%CI 1.43-21.02; p=0.015).

Detection of the JC virus genome in lung cancers: possible role of the T-antigen in lung oncogenesis. HO Abdel-Aziz, Y Murai, M Hong, T Kutsuna, H Takahashi, K Nomoto, S Murata, K Tsuneyama, Y Takano. Appl Immunohistochem Mol Morphol 2007 Dec;15(4):394-400. "To clarify whether JCV might have a potential role in the genesis of lung cancers, we investigated the presence of its genome in 62 tumors, along with 23 samples of normal lung tissue, targeting the T-antigen, VP, and Agnoprotein by nested polymerase chain reaction/Southern blotting followed by direct DNA sequencing... The T-antigen was detected in 25 of 62 lung cancers but only 4 of 23 normal lung samples (P=0.048). In total, the JCV genome was present in 33 of the lung cancers and 10 of the normal samples. Furthermore, T-antigen was found in cancer cells in metastatic lymph nodes in 3 of 4 cases (P=0.042) and was more frequently detected in adenocarcinomas than in squamous cell carcinomas (P=0.038)."

Merkel cell polyomavirus in non-small cell lung carcinomas from Chile. T Gheit, JP Muñoz, J Levican, C González, S Ampuero, B Parra, A Gaggero, AH Corvalán, M Meneses, M Tommasino, F Aguayo. Exp Mol Pathol 2012 Apr 16;93(1):162-166. 4/86 (4.7%) of non-small cell lung carcinomas were positive for Merkel cell polyomaviruses, one of which was actively expressing large T antigen transcripts.

A Possible Role for EBV

[Detection of Epstein-Barr virus in lung carcinoma tissue by in situ hybridization]. CM Li, GL Han, SJ Zhang. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2007 Sep;21(3):288-290. In 108 cases from Tanshan, China, "The positive rates of EBV infection in squamous cell carcinoma, adenocarcinoma, small cell carcinoma and large cell carcinoma were 35.9%, 31.6% 31.0%, 1/2, respectively."

Epstein-Barr virus microRNAs and lung cancer. J Koshiol, ML Gulley, Y Zhao, M Rubagotti, FM Marincola, M Rotunno, W Tang, AW Bergen, PA Bertazzi, D Roy, AC Pesatori, I Linnoila, D Dittmer, AM Goldstein, NE Caporaso, LM McShane, E Wang, MT Landi. Br J Cancer 2011 Jul 12;105(2):320-326. From the NCI. 48 cases, by microarray and real-time quantitative PCR (qPCR). "Although qPCR provided substantial evidence of EBV miRNAs in 7 out of 48 cases, only 1 of these 7 cases had detectable EBV DNA in tumour tissue. None had detectable EBV RNA or protein by histochemical stains."

[Study on EB virus infection, LMP1 and Bcl-2 expression in lung cancer patients]. CM Li, SJ Zhang, JH Zhu, GL Han. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2011 Aug;25(4):277-279. By in situ hybridization: "In 108 cases of lung cancer, 36 cases were EBER1 positive and 7 cases were LMP1 positive. The expression of Bcl-2 was higher in EBV positive lung cancer tissues than that in EBV negative."

Identification of Epstein-Barr virus-induced gene 3 as a novel serum and tissue biomarker and a therapeutic target for lung cancer. R Nishino, A Takano, H Oshita, N Ishikawa, H Akiyama, H Ito, H Nakayama, Y Miyagi, E Tsuchiya, N Kohno, Y Nakamura, Y Daigo. Clin Cancer Res 2011 Oct 1;17(19):6272-6286. 414 non-small cell lung cancers in microarray analysis; serum EBI3 levels from 274 lung cancer patients and 126 healthy volunteers by ELISA. "[A] high level of EBI3 expression was associated with a poor prognosis of lung cancer (P = 0.0014) and multivariate analysis confirmed it to be an independent prognostic factor (P = 0.0439). Serum levels of EBI3 in the training set were found to be significantly higher in lung cancer patients than in healthy volunteers; this result was also observed in the validation set."

History

"General interest in lung cancer developed considerably later in the United States than it did in Europe but cases were described (37) at the Massachusetts General Hospital in 1842 and 1850. Articles contributed by Lehlbach (38) in 1870 and by Loomis (39) in 1876 showed considerable familiarity with the disease. Delafield (40), the pathologist at Roosevelt Hospital, was well acquainted with primary lung cancer as early as 1868 as evidenced by his autopsy records. In the later decades of the 19th century the number of American articles increased including contributions by Pepper (41), Van Giesen (42), Ripley (43), Kemper (44), Janeway (45), Holland (46), Hodenpyl (47), and LeCount (48). On December 18, 1880, the Medical Record commented editorially that lung cancer would continue to interest pathologists despite the lack of specific treatment. The most important American article on lung cancer in the 19th century appeared in the New York Medical Journal on February 8, 1896. The author was Adler (49) whose monograph on the subject in 1912 has since become a medical classic. In the 1896 article, Adler repeatedly emphasized that lung cancer was not a rare disease in the United States but was rarely diagnosed. He urged physicians to become more familiar with its clinical manifestations and pathologists to do more meticulous work so as to better recognize the disease at autopsy." (Smoking and Disease: Etiological Perspective. Testimony of Milton B. Rosenblatt to the U.S. Senate Committee on Commerce, March 18, 1965.)

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cast 05-05-13