HPV Is Implicated in Esophageal Cancer

Detection of human papillomavirus DNA in cytologic specimens derived from esophageal precancer lesions and cancer. F Chang, O Shen, J Zhou, C Wang, D Wang, S Syrjänen, K Syrjänen. Scand J Gastroenterol 1990 Apr;25(4):383-388. 53 of 80 specimens (66.3%) from a high-risk area of China were positive for HPV.

Human papillomavirus involvement in esophageal precancerous lesions and squamous cell carcinomas as evidenced by microscopy and different DNA techniques. F Chang, S Syrjanen, Q Shen, L Wang, D Wang, K Syrjanen. Scand J Gastroenterol 1992 Jul;27(7):553-563. By light microscopy, HPV-suggestive lesions were found in 49.0% (25 of 51). By in situ hybridization, 43.1% (22 of 51) contained HPV DNA; and by PCR, DNA was found in three which were negative by ISH.

Infectious agents in the etiology of esophageal cancer. F Chang, S Syrjanen, L Wang, K Syrjanen. Gastroenterology 1992 Oct;103(4):1336-1348. Review.

Prognostic significance of human papillomavirus genomes (type-16, -18) and aberrant expression of p53 protein in human esophageal cancer. M Furihata, Y Ohtsuki, S Ogoshi, A Takahashi, T Tamiya, T Ogata. Int J Cancer 1993 May 8;54(2):226-230. 24/71 (34%) of patients with esophageal squamous-cell carcinoma from Kochi prefecture were positive for HPV DNA, "including 10 for HPV type-16 and 14 for HPV type-18; in contrast, none were positive for HPV-31 or -33."

Demonstration of human papillomavirus (HPV) type 30 in esophageal squamous-cell carcinomas by in situ hybridization (letter). F Chang, S Syrjänen, K Syrjänen. Int J Cancer 1993;55:171-173. HPV-30 was present in 8 (9.4%) of 85 HPV-positive esophageal carcinomas. "5 were infected with the HPV-30 as the single type, and 3 patients were co-infected with other HPV types, 1 with HPV 6/11 and 2 with HPV 16.... The original isolation of HPV 30 from a laryngeal squamous-cell carcinoma indicates that this virus can exert an oncogenic potential on epithelial cells. The identification of HPV 30 DNA in 2.2% (8/363) of esophageal squamous-cell carcinomas points to a causal role for this HPV type in the pathogenesis of esophageal carcinoma."

Screening for human papillomavirus infections in esophageal squamous cell carcinomas by in situ hybridization. F Chang, S Syrjanen, Q Shen, L Wang, K Syrjanen. Cancer 1993 Nov 1;72(9):2525-2530. 85 (23.4%) of esophageal squamous cell carcinomas from patients from a high-incidence area of China contained HPV DNA.

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. "HPV infection in human esophagus was first suggested in 1982 by Syrjanen et al., who found that 40% (24/60) of esophageal squamous cell carcinomas presented with histological changes identical to those of genital (HPV-induced) condylomas.... These results have been confirmed by others demonstrating HPV-suggestive lesions, HPV antigens as well as HPV DNA sequences in esophageal squamous cell lesions." The Kuopio Papillomavirus Research Group's work was virtually the only research on infection as the fundamental cause of chronic disease that the CTR funded - and then they never used the data.

High prevalence of human papillomavirus in squamous cell carcinoma and matched normal esophageal mucosa: assessment by polymerase chain reaction. PO Fidalgo, ML Cravo, PP Chaves, CN Leitao, FC Mira. Cancer 1995 Nov 1;76(9):1522-1528. 8/16 (50%) were positive for HPV-16 and 3/16 (18.8%) were positive for HPV-18.

Detection of human papillomavirus in esophageal squamous cell carcinoma. L Suzuk, AE Noffsinger, YZ Hui, CM Fenoglio-Preiser. Cancer 1996 Aug 15;78(4):704-710. Out of 110 tumors, they did not find any HPV in any specimen by ISH or by PCR.

Serologic association between human papillomavirus type 16 infection and esophageal cancer in Shaanxi Province, China. C Han, G Qiao, NL Hubbert, L Li, C Sun, Y Wang, M Yan, D Xu, Y Li, DR Lowy, JT Schiller. J Natl Cancer Inst 1996 Oct 16;88(20):1467-1471. "24% of the cancer patients were seropositive compared with 7% of the control subjects, yielding a sex- and age-adjusted OR of 4.5 (95% CI = 1.8-11.9). In general, the OR for esophageal cancer increased with increasing HPV16 seroreactivity."

p53 overexpression and human papillomavirus (HPV) infection in oesophageal squamous cell carcinomas derived from a high-incidence area in China. F Chang, S Syrjanen, L Wang, Q Shen, K Syrjanen. Anticancer Res 1997 Jan-Feb;17(1B):709-715.

Absence of human papillomavirus-16 and -18 DNA and Epstein-Barr virus DNA in esophageal squamous cell carcinoma. S Mizobuchi, H Sakamoto, Y Tachimori, H Kato, H Watanabe, M Terada. Jpn J Clin Oncol 1997 Feb;27(1):1-5. HPV DNA sequences were found in 3/36 patients (8.3%).

Low prevalence of human papillomavirus infection in esophageal squamous cell carcinomas from North America: analysis by a highly sensitive and specific polymerase chain reaction-based approach. JR Turner, LH Shen, CP Crum, PJ Dean, RD Odze. Hum Pathol 1997 Feb;28(2):174-178. Harvard Medical School researchers found only 1/51 (2%) HPV-positive ESCCs.

Human papillomavirus infection in esophageal carcinomas: a study of 121 lesions using multiple broad-spectrum polymerase chain reactions and literature review. M Poljak, A Cerar, K Seme. Hum Pathol 1998 Mar;29(3):266-271. They found no HPV in 121 ESCCs.

Infection of human papillomavirus (HPV) and Epstein-Barr virus (EBV) and p53 expression in human esophageal carcinoma. A Khurshid, N Kazuya, I Hanae, I Manabu. J Pak Med Assoc 1998 May;48(5):138-142. "HPV and EBV DNA were found in 25% and 0% of normal esophageal tissues and in 63% and 7% of esophageal carcinoma specimens, respectively."

Human papillomavirus involvement in esophageal carcinogenesis in the high-incidence area of China. A study of 700 cases by screening and type-specific in situ hybridization. F Chang, S Syrjanen, Q Shen, M Cintorino, R Santopietro, P Tosi, K Syrjanen. Scand J Gastroenterol 2000 Feb;35(2):123-130. "Of the 700 esophageal carcinomas, 118 (16.9%) were shown to contain HPV DNA sequences by screening ISH... Notably, 60.2% of the HPV-positive lesions contained DNA sequences other than HPV types 6, 11, 16, 18, 30, and 53."

Evaluation of HPV, CMV, HSV and EBV in esophageal squamous cell carcinomas from a high-incidence area of China. F Chang, S Syrjanen, Q Shen, M Cintorino, R Santopietro, P Tosi, K Syrjanen. Anticancer Res 2000 Sep-Oct;20(5C):3935-3940. HPV DNA sequences found in 17/101 (16.8%) of carcinomas. The three herpesviruses were not detected.

Human papillomavirus type 16 is an important infectious factor in the high incidence of esophageal cancer in Anyang area of China. T Li, Z-M Lu, K-N Chen, M Guo, H-P Xing, Q Mei, H-H Yang, JF Lechner, Y Ke. Carcinogenesis 2001 Jun;22(6):929-934. "Esophageal carcinoma is one of the major cancers in China. The area of Anyang is located at the foot of Tai Hang Mountain in Henan province and has the highest incidence and mortality of esophageal cancer in China. Extensive investigations on natural geographic environment, life habits and trace elements in the diet have failed to establish the etiology of esophageal cancer in this district." In volunteers, 72% in the high incident village and 37% in the low incident village were infected, mainly by HPV-16.

[Causal association between human papilloma virus infection and head and neck and esophageal squamous cell carcinoma]. Z Szentirmay, I Szántó, I Bálint, K Pólus, E Remenár, L Tamás, G Szentkúti, Z Melegh, P Nagy, M Kásler. Magy Onkol 2002;46(1):35-41. "Overall, HPV sequences were detected in 61 of 150 specimens. HPV DNA sequences were detected in 16/32 specimens in the oropharyngeal region, in 13/36 specimens in larynx and 32/82 specimens in esophagus. Papillomas contained only the episomal form of HPV 16.In the esophagus, the most common type was HPV 73. In all specimens examined, HPV 6/11 (4/150), HPV 16 (23/150), HPV 35 (1/150), HPV 45 (1/150), HPV 54 (1/150), HPV 58 (1/150), HPV 61 (1/150), HPV 66 (1/150), HPV 68 (2/150), HPV 70 (3/150), HPV 72 (1/150), HPV 73 (16/150), double HPV infection (2/150), and unidentified HPV type (4/150) was detected. Interestingly, HPV was found in all verrucous carcinomas and in 18/22 basaloid squamous cell carcinomas."

HPV infections and esophageal cancer. KJ Syrjanen. J Clin Pathol 2002;55(10):721-728. Review. "To date, 239 oesophageal squamous cell papillomas have been analysed in 29 separate studies using different HPV detection methods, with HPV being detected in 51 (21.3%) cases. Many more squamous cell carcinomas have been analysed: of the 1485 squamous cell carcinomas analysed by in situ hybridisation, 22.9% were positive for HPV DNA, as were 15.2% of the 2020 cases tested by the polymerase chain reaction."

Detection of human papillomavirus in esophageal carcinoma. ZY Shen, SP Hu, LC Lu, CZ Tang, ZS Kuang, SP Zhong, Y Zeng. J Med Virol 2002 Nov;68(3):412-416. In 176 esophageal cancer patients, for HPV type 6, 11, 16, and 18, "The incidence rate was 65.5%, 69.1%, and 60% in tissues of cancerous, paracancerous and normal mucosa, respectively. Further analysis of the distribution of HPV types in the three sections of tissues showed that the high-risk HPV types 16 and 18 were found mainly in the cancer cells (43.2%), whereas the low-risk HPV types 6 and 11 were seen mainly in the normal mucosa (52.3%). The total infection rate of the high-risk HPV types 16 and HPV 18 was the highest in cancerous tissues (54.5%), followed by paracancerous tissues (19.5%), and the lowest in normal mucosa (11.7%).

Expression of p21/WAF-1, status of apoptosis and p53 mutation in esophageal squamous cell carcinoma with HPV infection. M Hasegawa, I Ohoka, K Yamazaki, K Hanami, I Sugano, T Nagao, A Asoh, N Wada, K Nagao, Y Ishida. Pathol Int 2002 Jul;52(7):442-450. 20/48 (42%) of ESCCs were HPV-positive by PCR. 16 were positive for HPV16, 3 for HPV18, and one for both.

E6/E7 genes of human papilloma virus type 18 induced immortalization of human fetal esophageal epithelium. ZY Shen, S Cen, LY Xu, WJ Cai, MH Chen, J Shen, Y Zeng. Oncol Rep 2003;10:1431–1436.

Viral load of HPV in esophageal squamous cell carcinoma. HX Si, SW Tsao, CS Poon, LD Wang, YC Wong, AL Cheung. Int J Cancer 2003 Feb 10;103(4):496-500. "HPV infection was detected in 2-22.2% of samples. Infection with HPV-16 was again shown to be more common than that with HPV-18 among Chinese ESCC patients. The copy number of HPV-16 in these ESCC cases ranged from < or =1 to 157 copies/genome equivalent, with 65% of samples harboring fewer than 10 copies/genome equivalent. The median copy number of HPV-18 was 4.9/genome equivalent."

[Expression of HPV16-E6 and E7 oncoproteins in squamous cell carcinoma tissues of esophageal cancer and non-cancer tissues]. CL Xu, XL Qian, XS Zhou, QZ Zhao, YC Li. Ai Zheng 2004 Feb;23(2):165-168. "HPV16-E6 and E7 oncoproteins were determined using immunohistochemical staining in normal mucosa tissues (70 cases), dysplasia tissues (43 cases), and carcinoma tissues (18 cases). RESULTS: The positive rates of HPV16-E6 in the tissues of normal mucosa, dysplasia, and carcinoma of esophagus patients were 59.3%, 88.4%, and 83.3%,respectively; the positive rates of HPV16-E7 protein were 62.1%, 90.7%, and 88.9%, respectively. The positive rates of HPV16-E6 and E7 in dysplasia and carcinoma of esophagus were significantly higher than those in normal mucosa (P< 0.05). Double expression of HPV16-E6 and E7 in normal mucosa was 25.7%, while in dysplasia and carcinoma were 88.3% and 83.3%, respectively. CONCLUSION: HPV16-E6 and E7 are highly associated with esophageal squamous cell carcinogenesis. And cooperation of HPV16-E6 and E7 may play an important role in genesis of esophageal squamous carcinoma."

Esophageal squamous cell cancer in patients with head and neck cancer: Prevalence of human papillomavirus DNA sequences. EM de Villiers, K Gunst, H Stein, H Scherubl. Int J Cancer 2004 Mar 20;109(2):253-258. Fresh-frozen random esophageal biopsies from 60 patients screened for asymptomatic ESCC, and 21 paraffin-embedded specimens with pairs of HNC and ESCC. "HPV DNA sequences were detected in 66.7% of normal/inflammatory (34/51) and dysplastic and malignant (6/9) esophageal tissues from HNC patients being screened endoscopically. Similarly, in the second group of 21 patients with both HNC and ESCC, HPV DNA sequences were demonstrated in 13 (61.9%) of the HNC biopsies and in 14 (66.7%) of the ESCC biopsies. The prevalence of high-risk-type HPV 16 was low (5/51, 9.8%) in normal/inflammatory esophageal mucosa but higher (10/24, 47.6%) in ESCC. The low-risk HPV 11 was present in 37.3% (19/51) of normal/inflammatory, 66.7% (4/6) of dysplastic and 28.9% (13/45) of the carcinoma samples."

p53 polymorphism in human papillomavirus-associated Kazakh's esophageal cancer in Xinjiang, China. XM Lu, YM Zhang, RY Lin, XH Liang, YL Zhang, X Wang, Y Zhang, Y Wang, H Wen H. World J Gastroenterol 2004 Oct 1;10(19):2775-2778. 55 of 104 esophageal squamous cell carcinomas were positive for HPV16 E6.

p53 gene mutation and human papillomavirus (HPV) infection in esophageal carcinoma from three different endemic geographic regions of India. S Katiyar, S Hedau, N Jain, P Kar, MS Khuroo, J Mohanta, S Kumar, V Gopalkrishna, N Kumar, BC Das. Cancer Lett 2005 Jan 31;218(1):69-79. "Out of a total of 101 biopsy specimens of carcinoma esophagus analysed, the frequency of HPV was found to be the highest 14/32 (44%) in Dibrugarh followed by 33% (11/33) in Kashmir, but, interestingly, no high-risk HPV could be detected in New Delhi patients who showed the highest frequency (30.6%) of p53 mutation as against only 12.5% in Dibrugarh and 6.1% in Kashmir."

Evaluation of the prevalence of human papillomavirus and Epstein-Barr virus in esophageal squamous cell carcinomas. ID Lyronis, S Baritaki, I Bizakis, M Tsardi, DA Spandidos. Int J Biol Markers 2005 Jan-Mar;20(1):5-10. 17/30 (56%) of ESCC were positive for HPV, versus 6/27 (22.2%) normal samples (p < 0.001). All were negative for EBV.

Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival. AA Bahnassy, AR Zekri, S Abdallah, AM El-Shehaby, GM Sherif. Pathol Int 2005 Feb;55(2):53-62. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues, of 50 patients with esophageal cancer.

Human papillomavirus in squamous cell carcinoma of esophagus in a high-risk population. M Farhadi, Z Tahmasebi, S Merat, F Kamangar, D Nasrollahzadeh, R Malekzadeh. World J Gastroenterol 2005 Feb 28;11(8):1200-1203. 14/38 (36.8%) of ESCCs were positive for the HPV L1 gene, versus 5/38 (13.2%) of controls. Fewer cases and controls were positive for HPV-18 E6/E7 gene.

The relationship between HPV16 and expression of CD44v6, nm23H1 in esophageal squamous cell carcinoma. WK Liu, YL Chu, F Zhang, P Chen, F Cheng, H Wang, YY Jia, TY Ma. Arch Virol 2005 May;150(5):991-1001. 24 of 40 (60%) esophageal squamous cell carcinomas were positive for the HPV16 E6 gene in Shaanxi Province of China, a high-incidence area.

LMP7/TAP2 gene polymorphisms and HPV infection in esophageal carcinoma patients from a high incidence area in China. B Cao, X Tian, Y Li, P Jiang, T Ning, H Xing, Y Zhao, C Zhang, X Shi, D Chen, Y Shen, Y Ke. Carcinogenesis 2005 Jul;26(7):1280-1284. "HPV16 and 18 were identified by PCR. HPV infection was found in 207 cases (78.11%) and 203 controls (56.86%). Among the 207 HPV positive patients, HPV16 and/or 18 DNA was found in 186 individuals including 175 infected by HPV16 alone, 4 infected by HPV18 alone and 7 infected by both types. In the control group, among the 203 HPV positive individuals, 181 were infected by HPV16 and/or 18 including 178 infected by HPV16, 4 infected by HPV18 and 1 infected by both HPV16 and 18." For HPV types 16 and/or 18, OR = 2.33 (95% CI = 1.66–3.27, P < 0.0001) [low due to the high rate of infection in controls -cast.] "No significant differences between cases and controls in cigarette smoking and alcohol consumption were found."

Detection of human papillomavirus DNA in squamous cell carcinoma of the esophagus by auto-nested PCR. AP Souto Damin, AP Guedes Frazzon, D de Carvalho Damin, H Beck Biehl, L Abruzzi de Oliveira, R Auler, C Marroni, CO Alexandre. Dis Esophagus 2006;19(2):64-68. In 165 paraffin-embedded specimens, "HPV DNA was detected in 26 esophageal carcinomas (15.75%), but in none of the benign esophageal specimens (P < 0.05). Out of the 26 positive cases, 24 were HPV-16 and one was HPV-18. One tumor contained both HPV-16 and -18 DNA. Positive PCR results were confirmed by the amplified viral sequences."

Evidence of human papilloma virus infection and its epidemiology in esophageal squamous cell carcinoma. PF Yao, GC Li, J Li, HS Xia, XL Yang, HY Huang, YG Fu, RQ Wang, XY Wang, JW Sha. World J Gastroenterol 2006 Mar 7;12(9):1352-1355. "IHC revealed that the positive rate of PV was 75.0%, 68.18% and 72.5% respectively while the HPV (16/18-E6) positive rate was 45.0%, 36.36%, 37.5%, respectively in esophageal carcinoma tissue specimens from Henan emigrants, the local citizens and patients in Hubei Cancer Hospital. The PV and HPV (16/18-E6) were negative in all normal esophageal mucosa specimens.... In situ hybridization showed that the HPV (16/18) DNA positive rate was 30.0%, 31.8%, 25.0%, respectively in the 3 groups of samples. No positive hybridization signal was found in 40 normal esophageal mucosa specimens."

High-risk human papilloma virus (HPV) and survival in patients with esophageal carcinoma: a pilot study. M Dreilich, M Bergqvist, M Moberg, D Brattstrom, I Gustavsson, S Bergstrom, A Wanders, P Hesselius, G Wagenius, U Gyllensten. BMC Cancer 2006 Apr 18;6:94. 100 patients with esophageal carcinoma investigated for HPV types 16, 18, 31, 33, 39, 45, 52, 58, and 67."HPV 16 was detected in 16% of the patients; no other HPV type was detected. HPV 16 infection had no significant effect on survival (p = 0.72)."

[HPV-infection in esophageal cancer as possible predictive factor after neoadjuvant therapy] B Gabor, A Imdahl, L Gyorgy, O Pal. Magy Seb 2006 Apr;59(2):97-104. 6 of 26 [23%] of oesophageal cancers had HPV-16 or -18.

Relationship between HPV16/18 E6 and 53, 21WAF1, MDM2, Ki67 and cyclin D1 expression in esophageal squamous cell carcinoma: comparative study by using tissue microarray technology. ZL Qi, X Huo, XJ Xu, B Zhang, MG Du, HW Yang, LK Zheng, J Li, ZY Shen. Exp Oncol 2006 Sep;28(3):235-240. "In ESCC samples, 18.3% (11/60) were revealed HPV16/18 E6 positive by IHC, while 40.0% (24/60) HPV positive by ISH; HPV16/18 E6 expression was significantly higher than that of control samples."

No association between HPV infection and the neoplastic progression of esophageal squamous cell carcinoma: result from a cross-sectional study in a high-risk region of China. GF Gao, MJ Roth, WQ Wei, CC Abnet, F Chen, N Lu, FH Zhao, XQ Li, GQ Wang, PR Taylor, QJ Pan, W Chen, SM Dawsey, YL Qiao. Int J Cancer 2006 Sep 15;119(6):1354-1359. 702 subjects. "A multivalent HPV hybridization probe, Digene Hybrid Capture II (Gaithersburg, MD), which recognizes high-risk types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, was used to determine the HPV infection status of the cytologic specimens...Using a cutpoint of > or =3.0 pg/ml of HPV DNA to define a positive test, HPV positivity was identified in 13% (61/475) of subjects without squamous dysplasia, 8% (8/102) with mild dysplasia, 7% (6/83) with moderate dysplasia, 16% (6/38) with severe dysplasia and zero (0/4) with invasive ESCC."

Human papillomavirus in esophageal squamous cell carcinoma in Colombia and Chile. A Castillo, E Aguayo, C Koriyama, M Torres, E Carrascal, A Corvalan, JP Roblero, C Naquira, M Palma, C Backhouse, J Argandona, T Itoh, K Shuyama, Y Eizuru, S Akiba. World J Gastroenterol 2006 Oct 14;12(38):6188-6192. HPV types 16 and 18 were detected in 21 of 73 ESCC specimens (29%), by PCR with GP5+/GP6+ primer and confirmed by Southern blot.

Frequency of human papillomavirus infection in oesophageal squamous cell carcinoma in Iranian patients. AE Far, A Aghakhani, R Hamkar, A Ramezani, HF Pishbigar, S Mirmomen, MR Roshan, S Vahidi, V Shahnazi, Z Deljoodokht. Scand J Infect Dis 2007;39(1):58-62. 140 cases of oesophageal squamous cell carcinoma analyzed by PCR. "...50.7% were female and 49.3% were male, aged between 20 and 81 y. 33 tumour specimens (23.6%) and 12 (8.6%) non-involved tumour margins were HPV positive. From HPV positive tumour cases 36% were positive in tumour margins. The HPV positive cases were 21.7% male and 25.3% female. There is no correlation between presence and types of HPV with patients' gender and age. The frequency of HPV subtypes in tumoural regions was as follows: HPV-16, 60.6%; HPV-18, 30.3%; HPV-33, 6.1%; and HPV-31, 3%. We found only HPV-16 in tumour margins. Our results are consistent with HPV studies conducted in other high-risk areas for ESCC and provided further evidence to support a causal association of HPV infection with ESCC."

Human papillomavirus in high- and low-risk areas of oesophageal squamous cell carcinoma in China. K Shuyama, A Castillo, F Aguayo, Q Sun, N Khan, C Koriyama, S Akiba. Br J Cancer 2007 May 21;96(10):1554-1559. 26 oesophageal squamous cell carcinomas from Gansu, 33 from Shandong. "HPV DNA was detected in 17 cases (65%) in Gansu, where ESCC incidence is much higher than in Shandong, where HPV was positive in two samples (6%). HPV genotypes 16 and 18 were detected in 79 and 16% of HPV-positive samples, respectively."

p53 Codon 72 polymorphism, loss of heterozygosity and high-risk human papillomavirus infection in a low-incidence German esophageal squamous cell carcinoma patient cohort. A Pantelis, D Pantelis, P Ruemmele, A Hartmann, F Hofstaedter, R Buettner, F Bootz, R Stoehr. Oncol Rep 2007 May;17(5):1243-1248. 53 cases screened for high-risk HPV infection (HPV 16 and 18) with primer specific PCR and confirmed by sequencing. "Of 53 (17%) samples, 9 showed HPV 16 or 18 infection. We found no association between p53 codon 72 genotypes and increasing HPV infection rates."

Possible role of human papilloma virus infection in response to neoadjuvant therapy in patients with esophageal cancer. G Bognar, A Imdahl, G Ledniczky, P Ondrejka. Hepatogastroenterology 2008 Jan-Feb;55(81):93-97. From 26 esophageal cancer patients undergoing CRX and surgery. Polymerase chain reaction (PCR) and Southern Blot hybridization was used to detect HPV-infection (HPV-16 and -18).... Six patients had HPV-infection (3 from the CR- and 3 from PR-group)."

No association of high-risk human papillomavirus with esophageal squamous cell carcinomas among Koreans, as determined by polymerase chain reaction. JS Koh, SS Lee, HJ Baek, YI Kim. Dis Esophagus 2008;21(2):114-117. "129 formalin-fixed, paraffin-embedded tumor specimens, eight fresh tumor tissues and 40 normal esophageal tissues were screened for HPV infection by polymerase chain reaction using consensus primers for HPV types 16, 18, 31, 33, 35, 52b and 58 and type 16-specific primers.... consensus and type 16-specific primers failed to detect HPV DNA sequences in any of the esophageal samples."

K-ras Mutation, HPV Infection and Smoking or Alcohol Abuse Positively Correlate with Esophageal Squamous Carcinoma. LD Lyronis, S Baritaki, I Bizakis, E Krambovitis, DA Spandidos. Pathol Oncol Res 2008;14(3):267-273. 30 ESCC and 32 normal esophageal specimens; no information on what types of HPV were tested for, and issue of confounding by undetected infection is not addressed. "The increased risk of esophageal cancer was correlated with tobacco use (OR = 3.5, P < 0.023) and alcohol abuse (OR = 7.22, P < 0.001), accompanied with the high incidence of the k-ras codon 12 mutation (22%, OR = 1.77 and 21%, OR = 1.52), respectively. A similar positive association was seen in human papilloma virus (HPV)-infected patients (OR = 5.66, P < 0.003)."

Human papillomavirus in esophageal squamous cell carcinoma of the high-risk Kazakh ethnic group in Xinjiang, China. XM Lu, S Monnier-Benoit, LZ Mo, SY Xu, JL Prétet, Z Liu, DA Vuitton, C Mougin. Eur J Surg Oncol 2008 Jul;34(7):765-770. 67 primary ESCC patients. "Twenty cancer patients (30%) had HPV DNA detected in collected specimens. Interestingly, 14 patients (21%) had HPV only in the tumor and six (9%) had HPV only in the normal esophageal tissue. Overall, HPV16 was the viral type most frequently detected being present in eight out of 20 positive cases (40%). No correlation between the presence of HPVs and the gender or ESCC grade was observed."

[Detection of human papillomavirus in tissues of esophageal carcinomas by polymerase chain reaction]. SY Li, Y Li, LD Wang, XZ Wu, L Zhou, XY Zhao, HT Liu, Y Zeng. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2008 Aug;22(4):251-253. 29/31 esophageal carcinoma samples from Henan Province were HPV positive; 19 were HPV16E6 (61.3%) and 8 were HPV18 E6 positive (25.8%).

K-ras mutation, HPV infection and smoking or alcohol abuse positively correlate with esophageal squamous carcinoma. ID Lyronis, S Baritaki, I Bizakis, E Krambovitis, DA Spandidos. Pathol Oncol Res 2008 Sep;14(3):267-273. 30 ESCC samples and 32 normal esophageal specimens, HPV OR = 5.66, P < 0.003. No information on HPV types or percentage positive.

Identification of human papillomavirus in esophageal squamous papillomas. OL Bohn, L Navarro, J Saldivar, S Sanchez-Sosa. World J Gastroenterol 2008 Dec 14;14(46):7107-7111. "HPV was detected in 14 of 16 cases (87.5%) by ACISH: Twelve showing a diffuse and complete nuclear staining pattern (indicating the episomal state of the HPV viral genome, Figure 1A) and two a nuclear granular pattern (indicating the integrated form of the HPV viral genome, Figure 1B). HPV DNA was identified by PCR in 12 of 14 cases (85.7%). Infection by a low risk type HPV (6/11) was detected in 10 of 14 cases, whereas two of the 14 cases were infected by a high risk HPV type (16). Both high risk cases showed a granular staining pattern on ACISH, suggesting viral genomic infection. In two cases, ACISH demonstrated a diffuse pattern and HPV was not documented by PCR."

[Meta analysis on etiological relationship between human papillomavirus and esophageal carcinoma]. SY Li, Y Li, LP Shen, XZ Wu, XY Zhao, L Zhou, HT Liu, Y Zeng. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2009 Apr;23(2):85-87. Metaanalysis of published articles in Chinese. 460 of 980 specimens (46.9%) were positive for HPV by PCR, varying from 8.3% to 69.8% in various locations.

[Detection of human papillomavirus in esophageal carcinoma tissues from Baoding City of Hebei Province]. XY Zhao, SY Li, Y Li, XL Wang, YL Li, XZ Wu, L Zhou, HT Liu, Y Zeng. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2009 Apr;23(2):91-93. "37 from 42 esophageal carcinoma samples were HPV positive and the rate was 88.1%. Among the samples detected, 19 were HPV16 E6 positive and rate was 45.2%, eight were HPV18 E6 positive and rate was 19.0%."

Human papilloma virus and esophageal carcinoma in a Latin-American region. R Herrera-Goepfert, M Lizano, S Akiba, A Carrillo-García, M Becker-D'Acosta. World J Gastroenterol 2009 Jul 7;15(25):3142-3147. "HPV was detected in 15 (25%) of ESCCs. HPV-16 was the most frequently observed genotype, followed by HPV-18; HPV-59 was also detected in one case.... HPV presence in ESCC was not significantly associated with gender, age, alcohol consumption, smoking, anatomic location, or histologic grade. All patients belonged to low and very low socioeconomic strata, and were diagnosed at advanced disease stage." Males were most often affected.

Characterization of Seven Novel Human Papillomavirus Types Isolated from Cutaneous Tissue, but also Present in Mucosal Lesions. EM de Villiers, K Gunst. J Gen Virol 2009 Aug;90(Pt 8):1999-2004. HPV 10, Alpha-papillomavirus, and Beta-papillomaviruses HPV 98, HPV 99, HPV 100, HPV 104, HPV 105 and HPV 113 were discovered in skin, "but HPV 98, HPV 100, HPV 104 and HPV 113 were also detected in malignant esophageal and oral lesions. The general prevalence of these HPV types in lesions is infrequent."

[A 1:2 matched case-control study on the interaction of HPV16E6 and HLA-DR9 allele to esophageal cancer in Kazakh ethnicity, Xinjiang]. PH Liao, JM Qin, TX Zeng, F Li, JF Cai, L He. Zhonghua Liu Xing Bing Xue Za Zhi 2009 Sep;30(9):951-954. 63 cases, 126 matched controls. "HPV16E6 infection and HLA-DR9 allele positive status were the risk factors for EC, with OR values as 2.67 (95%CI: 1.38 - 5.17) and 3.83 (95%CI: 1.48 - 9.96) respectively. The rate of HPV16E6 infection in individuals with HLA-DR9 allele was different from the ones who were HLA-DR9 allele free (chi(2) = 7.57, P = 0.006), with OR value as 5.79 (95%CI: 1.53 - 21.87). In the controls, the rates of HPV16E6 infection were 22.2% and 16.2% among individuals with HLA-DR9 allele atatus as positive or negative, and without statistically significant difference."

Transcription factor AP-1 in esophageal squamous cell carcinoma: alterations in activity and expression during human Papillomavirus infection. S Hussain, AC Bharti, I Salam, MA Bhat, MM Mir, S Hedau, MA Siddiqi, SF Basir, BC Das. BMC Cancer 2009 Sep 16;9:329. 19% (14 of 75) histopathologically-confirmed esophageal cancer were positive for HPV type 16, versus 0 of 75 adjacent normal tissue biopsies. No other HPV types were found.

Detection of HPV DNA in esophageal cancer specimens from different regions and ethnic groups: a descriptive study. X Wang, X Tian, F Liu, Y Zhao, M Sun, D Chen, C Lu, Z Wang, X Shi, Q Zhang, D Zhang, Z Shen, F Li, CC Harris, H Cai, Y Ke. BMC Cancer 2010 Jan 16;10:19. 244 of 435 samples (56.1%) tested positive for HPV L1. "Significant differences in detection rate were observed neither among the three areas of China nor between China and the US. HPV6, 16, 18, 26, 45, 56, 57, and 58 were identified in L1 positive samples. HPV16 and 57 were the most common types in all regions, followed by HPV26 and HPV18. CONCLUSIONS: HPV infection is common in esophageal carcinoma independent of region and ethnic group of origin. Findings in this study raise the possibility that HPV is involved in esophageal carcinogenesis. Further investigation with a larger sample size over broader geographic areas may be warranted." Detection rates were similar in adenocarcinomas and squamous cell carcinomas. HPV load is lower in esophageal than in cervical cancer, which results in false negatives in other studies.

Mechanisms

The genetic events of HPV-immortalized esophageal epithelium cells. ZY Shen, LY Xu, XH Chen, WJ Cai, J Shen, JY Chen, TH Huang, Y Zeng. Int J Mol Med 2001 Nov;8(5):537-542. Changes of chromosomes, telomere length, telomerase activity and certain gene expressions in epithelial cells from embryonic esophagus induced by genes E6E7 of HPV type 18, cultivated without co-carcinogens. "Telomere length sharply shortened from normal fetal esophagus to the 10th and 31st passage step by step, but was stable from the 31st to the 60th passage and the telomerase activities measured were expressed at late two passages."

[Study on human papillomavirus infection and loss of heterozygosity of microsatellite in esophageal cancer]. M Liu, HC Zeng, XL Zhang, J Zhu, JF Huang, X Zhang, M Xia. Zhonghua Liu Xing Bing Xue Za Zhi 2007 Dec;28(12):1203-1206. "High frequency of LOH was observed among chromosome arms 3p, 9p, 13q, 17p and 17q. The frequency of LOH was significantly higher at loci D13S260 and D6S497 in HPV positive specimens, comparing with HPV negative ones."

Socioeconomic status and esophageal cancer

Socio-economic status and oesophageal cancer: results from a population-based case–control study in a high-risk area. F Islami, F Kamangar, D Nasrollahzadeh, K Aghcheli, M Sotoudeh, B Abedi-Ardekani, S Merat, S Nasseri-Moghaddam, S Semnani, A Sepehr, J Wakefield, H Møller, CC Abnet, SM Dawsey, P Boffetta, R Malekzadeh. Int J Epidemiol 2009;38(4):978-988. In Golestan Province, Iran, with highest rate in the world, "The strongest inverse association was found with education. Compared with no education, the adjusted odds ratios (95% confidence intervals) for primary education and high school or beyond were 0.52 (0.27-0.98) and 0.20 (0.06-0.65), respectively."

A possible role for JC virus

Detection of JC virus DNA sequences and expression of viral T antigen and agnoprotein in esophageal carcinoma. L Del Valle, MK White, S Enam, SP Oviedo, MQ Bromer, RM Thomas, HP Parkman, K Khalili. Cancer 2005 Feb 1;103(3):516-527. "Using immunohistochemistry, JCV T antigen was detected in 10 of 19 carcinomas (53%), agnoprotein was detected in 8 carcinomas (42%), p53 tumor suppressor was detected in 11 carcinomas (58%), and beta-catenin was detected in 4 carcinomas (21%). Zero of 51 normal, benign, and premalignant esophageal samples expressed viral proteins. Laser-capture microdissection verified the presence and specificity of JCV DNA sequences. beta-Catenin and p53 were colocalized with JCV T-antigen in the nuclei of neoplastic cells."

See also:

Confounding By Infection - why studies that don't include full detection of HPV (and other causal infections) are defective, and falsely blame smoking and other non-causal associations.

The Lie That p53 Mutations Are the Mechanism Behind Lung Cancer - this is because p53 mutations happen after maligancy has occurred, and the point is relevant to other cancers as well.

cast 06-04-10