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.

Chang - Scand J Gastroenterol 1990 full article / tobacco document

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.

Chang - Gastroenterol 1992 full article / tobacco document

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

Chang - Gastroenterology 1992 full article / tobacco document

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."

Furihata - Int J Cancer 1993 abstract / PubMed

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."

Chang - Int J Cancer 1993 full article / tobacco document

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.

Chang - Cancer 1993 full article / tobacco document

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.

Syrjanen proposal, 1993 / tobacco document

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.

Fidalgo - Cancer 1995 abstract / PubMed

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.

Suzuk - Cancer 1996 abstract / PubMed

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."

Han / JNCI 1996 full article (pdf, 5 pp)

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.

Chang - Anticancer Res 1997 abstract / PubMed

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%).

Mizobuchi / Jpn J Clin Oncol 1997 full article

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.

Turner - Hum Pathol 1997 abstract / PubMed

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.

Poljak - Hum Pathol 1998 abstract / PubMed

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."

Khurshid - J Pak Med Assoc 1998 abstract / PubMed

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."

Chang - Scand J Gastroenterol 2000 abstract / PubMed

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.

Chang - Anticancer Res 2000 abstract / PubMed

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.

Li / Carcinogenesis 2001 full article

[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."

Szentirmay - Magy Onkol 2002 abstract / PubMed

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."

Syrjanen / J Clin Pathol 2002 full article

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%).

Shen - J Med Virol 2002 abstract / PubMed

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.

Hasegawa - Pathol Int 2002 abstract / PubMed

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.

Shen - Oncol Rep 2003 abstract / PubMed

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."

Si - Int J Cancer 2003 abstract / PubMed

[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."

Xu - Ai Zheng 2004 abstract / PubMed

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."

de Villiers - Int J Cancer 2004 abstract / PubMed

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.

Lu / World J Gastroenterol 2004 full article

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."

Katiyar - Cancer Lett 2005 abstract / PubMed

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.

Lyronis - Int J Biol Markers 2005 abstract / PubMed

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.

Bahnassy - Pathol Int 2005 abstract / PubMed

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.

Farhadi / World J Gastroenterol 2005 full article

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.

Liu - Arch Virol 2005 abstract / PubMed

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."

Cao / Carcinogenesis 2005 full article

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."

Souto Damin - Dis Esophagus 2006 abstract / PubMed

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."

Yao - World J Gastroenterol 2006 full article

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)."

Dreilich - BMC Cancer 2006 full article / PubMed Central
Dreilich / BMC Cancer 2006 full article

[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.

Gabor - Magy Seb 2006 abstract / PubMed

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."

Qi - Exp Oncol 2006 abstract / PubMed

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."

Gao - Int J Cancer 2006 abstract / PubMed

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.

Castillo - World J Gastroenterol 2006 abstract / PubMed
Castillo / World J Gastroenterol 2006 full article

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."

Far - Scand J Infect Dis 2007 abstract / PubMed

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."

Shuyama - Br J Cancer 2007 abstract / PubMed

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."

Pantelis - Oncol Rep 2007 abstract / PubMed
Pantelis / Oncol Rep 2007 full article pdf download page

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)."

Bognar - Hepatogastroenterology 2008 abstract / PubMed

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."

Koh - Dis Esophagus 2008 abstract / PubMed

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)."

Lyronis - Pathol Oncol Res 2008 abstract / PubMed

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."

Lu - Eur J Surg Oncol 2008 abstract / PubMed

[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%).

Li - Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2008 abstract / PubMed

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.

Lyronis - Pathol Oncol Res 2008 abstract / PubMed

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."

Bohn / World J Gastroenterol 2008 full article

[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.

Li - Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2009 abstract / PubMed

[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%."

Zhao - Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2009 abstract / PubMed

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.

Herrera-Goepfert / World J Gastroenterol 2009 full article
Herrera-Goepfert - World J Gastroenterol 2009 full article / PubMed Central

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."

de Villiers - J Gen Virol 2009 abstract / PubMed

[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."

Liao - Zhonghua Liu Xing Bing Xue Za Zhi 2009 abstract / PubMed

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.

Hussain / BMC Cancer 2009 full article
Hussain - BMC Cancer 2009 full article / PubMed Central

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.

Wang - BMC Cancer 2010 full article / PubMed Central
Wang / BMC Cancer 2010 full article

High-risk human papillomavirus in esophageal squamous cell carcinoma. A Antonsson, DJ Nancarrow, IS Brown, AC Green, PA Drew, DI Watson, NK Hayward, DC Whiteman; Australian Cancer Study. Cancer Epidemiol Biomarkers Prev 2010 Aug;19(8):2080-2087. 8 of 222 (3.6%) ESCC patients were positive for HPV by PCR, versus 0 of 55 healthy controls.

Antonsson - Cancer Epidemiol Biomarkers Prev 2010 abstract / PubMed

Comparison of prevalence, viral load, physical status and expression of human papillomavirus-16, -18 and -58 in esophageal and cervical cancer: a case-control study. D Zhang, Q Zhang, L Zhou, L Huo, Y Zhang, Z Shen, Y Zhu. BMC Cancer 2010 Nov 26;10:650. 70 esophageal squamous cell cancers, and 60 controls, 39 cervical squamous cell cancers and 54 controls. 50.0% of ESCCs were positive for HPV, mainly types 16, 18 and 58. Based on ratios of HPV E2 expression to E6/7 expression, "for ESCC patients, the frequency of HR-HPV integration was higher than that for ESCC controls (rs = 0.405, P = 0.002)."

Zhang - BMC Cancer 2010 full article / PubMed Central

Association of defective HLA-I expression with antigen processing machinery and their association with clinicopathological characteristics in Kazak patients with esophageal cancer. H Ayshamgul, H Ma, S Ilyar, LW Zhang, A Abulizi. Chin Med J (Engl) 2011 Feb;124(3):341-346. "HPV16 were detected in 19 out of 50 (38.0%) of the Kazak esophageal cancer patients. There were 19 cases of HPV16 infection with defective expression of HLA-I, and 16 cases negative for HPV16 expression with normal expression HLA-I among the 50 esophageal cancer patients. The reduced expression of HLA-I in esophageal squamous carcinoma positively correlated with HPV16 infection (r=0.360 and P=0.003)."

Ayshamgul / Chin Med J (Engl) 2011 full article

Assessment of Immunohistochemistry for p16INK4 and High-Risk HPV DNA by In Situ Hybridization in Esophageal Squamous Cell Carcinoma. SM Malik, DT Nevin, S Cohen, JL Hunt, JP Palazzo. Int J Surg Pathol 2011 Feb;19(1):31-34. "20 cases of ESCC (63%) showed only cytoplasmic staining for p16(INK4), and 11 cases (34%) showed both cytoplasmic and nuclear staining for p16(INK4); 4 cases (13%) showed no staining for p16(INK4). None of the p16(INK4)-positive cases were positive for high-risk HPV by ISH."

Malik - Int J Surg Pathol 2010 abstract / PubMed

[Study of human papillomavirus in biopsy tissue specimens of esophageal carcinomas in Linzhou city]. MC Cui, Y Li, X He, XL Wang, LD Wang, HT Liu. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2011 Feb;25(1):39-41. "All 18 biopsy samples were HPV positive, and HPV 16 was detected in 13 of the 18 samples, HPV 18 was detected in 4 of the 18 samples."

Cui - Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi 2011 abstract / PubMed

Infection and integration of human papillomavirus in esophageal carcinoma. QY Zhang, DH Zhang, ZY Shen, LY Xu, EM Li, WW Au. Int J Hyg Environ Health 2011 Mar;214(2):156-161. 106 esophageal tumor tissues and paired adjacent normal tissues, 100 normal controls. "The detection rates of HPV DNA in EC and tumor-adjacent tissue were significantly higher than that in normal controls (77.4% and 80.2% vs. 33.0%). HPV infection was mainly found in adults, ages 35-47 years old, and the infection rate was negatively associated with the age of EC patients (P-trend<0.05). In addition, the HPV infection rates in patients who smoked was 3.27 times higher than in non-smoking patients (84.9% vs. 67.4%, P<0.05) but was not associated with gender, alcohol consumption, tumor grade or lymph-node metastasis of EC patients. The distribution of HPV genotypes in patients from high to low proportion was HPV-16, -58, -18, -33, -31 and -11. Infection with multiple HPV genotypes mainly included HPV-16/-18 and HPV-16/-33. The integration rate of HPV-16 in EC tissue was higher than that in tumor-adjacent and control tissues (93.4% vs. 50.9% and 45.5%)."

Zhang - Int J Hyg Environ Health 2011 abstract / PubMed

Prevalence and association of human papillomavirus 16, Epstein-Barr virus, herpes simplex virus-1 and cytomegalovirus infection with human esophageal carcinoma: A case-control study. DH Zhang, QY Zhang, CQ Hong, JY Chen, ZY Shen, Y Zhu. Oncol Rep 2011 Jun;25(6):1731-1738. 70 EC cases, 100 normal mucosa controls. "The infection rates of HPV-16, HSV-1 and EBV were 40.0, 30.0 and 30.0%, respectively, in EC mucosa, and were significantly higher than those in normal mucosa. However, no CMV DNA was detected in either EC or normal mucosa. HPV-16 or EBV infection was mainly detected in EC patients 48-58 years old, and the infection rate was positively associated with pathological grade of EC (P<0.05). Tobacco smoking and alcohol consuption were high risk factors for HPV-16 infection for male patients [odds ratio (OR), 5.9; 95% confidence interval (CI), 1.4-24.6; OR=3.8; 95% CI, 1.1-13.8]."

Zhang - Oncol Rep 2011 abstract / PubMed

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. 9.4% of 181 esophageal carcinomas from Japan, Korea, Singapore and Taiwan were positive for HPV by PCR and ISH. Most were HPV types 16/18.

Goto - J Med Virol 2011 abstract / PubMed

Evaluation of human papilloma virus infection in patients with esophageal squamous cell carcinoma from the caspian sea area, north of iran. Y Yahyapour, M Shamsi-Shahrabadi, M Mahmoudi, S Siadati, SS Shahryar, J Shokri-Shirvani, H Mollaei, SH Monavari. Asian Pac J Cancer Prev 2012;13(4):1261-1266. 46 upper, 69 middle and 62 lower third esophageal squamous cell carcinoma specimens. "28.3% of upper, 29% of middle and 25.8% of lower third of ESCC samples were positive for HPV DNA."

Yahyapour - Asian Pac J Cancer Prev 2012 abstract / PubMed

Prevalence of human papillomavirus (HPV) in oesophageal squamous cell carcinoma in relation to anatomical site of the tumour. HE Löfdahl, J Du, A Näsman, E Andersson, CA Rubio, Y Lu, T Ramqvist, T Dalianis, J Lagergren, H Dahlstrand. PLoS One 2012;7(10):e46538. "Among 204 patients, 20 (10%) had tumours harbouring HPV DNA, almost all (90%) of HPV high-risk type, mainly HPV16. Tumours containing HPV were not overrepresented in the upper compared to the middle or lower third of the oesophagus (odds ratio 0.6, 95% confidence interval 0.2-1.9). P16(INK4a) expression was similarly common (24% and 16%) in the HPV-positive and HPV-negative groups."

Löfdahl - PLoS One 2012 full article / PubMed CentralLöfdahl / PLoS One 2012 full article

HLA-DRB1*1501 and HLA-DQB1*0301 alleles are positively associated with HPV16 infection-related Kazakh esophageal squamous cell carcinoma in Xinjiang China. J Hu, L Li, L Pang, Y Chen, L Yang, C Liu, J Zhao, B Chang, Y Qi, W Liang, F Li. Cancer Immunol Immunother 2012 Nov;61(11):2135-2141. "HPV16 infection rate in Kazakh ESCC case group was 41 %, significantly higher than that of control group 14 % (OR = 3.62; 95 % CI, 2.15-6.09; P < 0.001). A positive association between ESCC and HLA-DRB1*1501 (OR = 2.46, P < 0.0125) or HLA-DQB1*0301 (OR = 3.34, P < 0.0125) alleles was observed. Similar tendencies were observed for HLA-DRB1*1501 (OR = 3.095, P < 0.0125) and HLA-DQB1*0301 (OR = 2.410, P < 0.0125) alleles with HPV16-positive ESCC."

Hu - Cancer Immunol Immunother 2012 abstract / PubMed

HPV infection in Brazilian patients with esophageal squamous cell carcinoma: Interpopulational differences, lack of correlation with surrogate markers and clinicopathological parameters. S Herbster, CT Ferraro, NK Koff, A Rossini, CD Kruel, NA Andreollo, DC Rapozo, TC Blanco, PA Faria, PT Santos, RM Albano, TD Simão, LF Pinto. Cancer Lett 2012 Dec 29;326(1):52-58. HPV was present in 13% of 264 ESCCs. "Most HPV positive tumors were infected with HPV16, but this was not associated with p16 expression, TP53 mutation status, patient age, amount of tobacco or alcohol consumption, or overall survival."

Herbster - Cancer Lett 2012 abstract / PubMed

Geographic origin is a significant determinant of human papillomavirus prevalence in oesophageal squamous cell carcinoma: Systematic review and meta-analysis. K Syrjänen. Scand J Infect Dis 2013 Jan;45(1):1-18. "These 152 studies covered a total of 10,234 ESCC cases, analysed by different HPV detection methods in different geographic regions. Of these 10,234 cases, 3135 (30.6%) tested HPV-positive, translating to an effect size of 0.372 (95% CI 0.360-0.384; fixed effects model) and 0.290 (95% CI 0.251-0.31; random effects model)... Conclusions: These meta-analysis results indicate that the reported wide variability in HPV detection rates in ESCC is not due to the HPV detection techniques, but is explained by the geographic origin of the study. These data substantiate the recently elaborated concept that ESCC might have a different aetiology in low-incidence and high-incidence geographic regions, HPV playing an important role only in the latter."

Syrjänen - Scand J Infect Dis 2013 abstract / PubMed

Viral load of HPV 16/18 in esophageal squamous cell carcinoma in three ethnic groups living in Xinjiang Autonomous Region, China. T Liu, Q Liu, M Liang, S Zheng, XL Li, X Lu, I Sheyhidin. Mol Biol Rep 2013 Feb;40(2):2045-2052. 52 / 253 samples were positive for HPV. All were HPV 16, with 6 co-infected with HPV 18.

Liu - Mol Biol Rep 2013 abstract / PubMed

High prevalence of human papillomavirus in esophageal squamous cell carcinoma: a study in paired samples. K Vaiphei, R Kochhar, S Bhardawaj, U Dutta, K Singh. Dis Esophagus 2013 Apr;26(3):282-287. HPV was positive in 20/23 (87%) patients. Most had more than one viral type. "HPV52 was the most common observed in 14 (61%) males and two (9%) females. Other common viruses were HPV55, 39, and 59. Smoking had a significant association with viral positivity. p63 and p16 oncoproteins correlated with degree of tumor differentiation but not with viral status."

Vaiphei - Dis Esophagus 2013 abstract / PubMed

The role of inflammation in HPV infection of the Oesophagus. G Schäfer, S Kabanda, B van Rooyen, MB Marušič, L Banks, MI Parker. BMC Cancer 2013 Apr 9;13:185. 114 OSCC biopsies and corresponding normal tissue. HPV DNA was found in about 9%, predominantly HPV18... "[A]lthough the carcinogen benzo-α-pyrene facilitated HPV pseudovirion uptake into cells in culture, HPV infectivity was independent of inflammation and seems to play only a minor role in oesophageal cancer."

Schäfer - BMC Cancer 2013 full article / PubMed Central
Schäfer / BMC Cancer 2013 full article

Human papillomavirus was not detected by PCR using multiple consensus primer sets in esophageal adenocarcinomas in Chinese patients. S Feng, J Zheng, X Du, Y Tan, H Yang, H Zhang, Z Zhang. J Med Virol 2013 Jun;85(6):1053-1057. 0/57 esophageal adenocarcinoma specimens were positive for HPV.

Feng - J Med Virol 2013 abstract / PubMed

Transcriptionally Active Human Papillomavirus Is Strongly Associated With Barrett's Dysplasia and Esophageal Adenocarcinoma. S Rajendra, B Wang, ET Snow, P Sharma, D Pavey, N Merrett, MJ Ball, T Brain, R Fernando, IK Robertson. Am J Gastroenterol 2013 Jul;108(7):1082-1093. "Of the 261 patients, 81 were positive for HPV DNA. In controls and BE, the virus was mostly detected at the transformation zone. Compared with controls (18.0%), HPV positivity was significantly more common in BD (68.6%, incidence rate ratio (IRR) 2.94, 95% confidence interval (CI) 1.78-4.85, P<0.001) and EAC (66.7%, IRR 2.87, 95% CI 1.69-4.86, P<0.001), but not in BE (22.1%, IRR 1.06, 95% CI 0.60-1.85, P=0.85). Of the patients, 92.6% were high-risk (HR) HPV, i.e., types 16 and 18. Again, p16INK4A positivity was greatest in BD and EAC and much less in BE patients (44.1%, IRR 17.0 (95% CI 4.86-59.6, P<0.001), 44.4%, 17.0 (95% CI 4.87-59.4, P<0.001), and 10.6%, 3.93 (95% CI 1.01-15.3, P=0.048) respectively). In 66 HPV DNA-positive patients tested for E6/E7 mRNA, none of the control (n=16) or BE (n=13) individuals were positive, whereas 9/22 BD and 9/15 EAC patients demonstrated oncogene expression (P<0.001). When HPV DNA, p16INK4A, and E6/E7 mRNA were all positive, there was a very strong association with disease severity (SCJ: odds ratio (OR) 104, 95% CI 20.3-529, P<0.001; lesion: OR 62.2, 95% CI 12.4-311, P<0.001) than when all were negative."

Rajendra - Am J Gastroenterol 2013 abstract / PubMed

The aetiological role of human papillomavirus in oesophageal squamous cell carcinoma: a meta-analysis. SS Liyanage, B Rahman, I Ridda, AT Newall, SN Tabrizi, SM Garland, E Segelov, H Seale, PJ Crowe, A Moa, CR Macintyre. PLoS One 2013 Jul 24;8(7):e69238. 1223 cases from 21 studies. "From all OSCC specimens included in this meta-analysis, 35% (426/1223) were positive for HPV DNA. The pooled OR for an HPV-OSCC association was 3.04 (95% CI 2.20 to 4.20)... Studies conducted in countries with low to medium OSCC incidence showed a stronger relationship (OR 4.65, 95% CI 2.47 to 8.76) than regions of high OSCC incidence (OR 2.65, 95% CI 1.80 to 3.91)."

Liyanage - PLoS One 2013 full article / PubMed Central
Liyanage / PLoS One 2013 full article

No evidence of HPV DNA in esophageal squamous cell carcinoma in a population of Southern Brazil. LC Antunes, JC Prolla, A de Barros Lopes, MP da Rocha, RB Fagundes. World J Gastroenterol 2013 Oct 21;19(39):6598-603. 51 ESCC biopsies, and various others. "HPV DNA was negative in all the 183 samples tested: 52 with ESCC, 9 with esophagitis and 122 with normal esophageal mucosa."

Antunes - World J Gastroenterol 2013 full article / PubMed Central
Antunes / World J Gastroenterol 2013 full article

Human papillomavirus types 16 and 18 in esophagus squamous cell carcinoma: a meta-analysis. F Yong, N Xudong, T Lijie. Ann Epidemiol 2013 Nov;23(11):726-734. 5755 cases of ESCC from 68 studies. "Overall, 11.67% (95% CI, 7.74%-16.21%) of ESCC cases harbored HPV-16 and 1.82% (95% CI, 0.90%-2.95%) harbored HPV-18. In addition, meta-analysis of 10 case-control studies showed a significant increase in ESCC risk with HPV-16 infection (summary ORs = 3.55; 95% CIs, 2.05%-6.14%). However, this increased risk in ESCC was not made for HPV-18 infection (summary ORs = 1.25; 95% CIs, 0.46%-3.43%)."

Yong - Ann Epidemiol 2013 abstract / PubMed

Evidence for the aetiology of human papillomavirus in oesophageal squamous cell carcinoma in the Chinese population: a meta-analysis. SS Liyanage, B Rahman, Z Gao, Y Zheng, I Ridda, A Moa, AT Newall, H Seale, Q Li, JF Liu, CR Macintyre. BMJ Open 2013 Nov 15;3(11):e003604. "Of a total of 1177 OSCC and 1648 oesophageal control samples, 55% (642/1177) of cancer specimens and 27% (445/1648) of control samples were positive for HPV DNA. A positive strong association between HPV DNA and OSCC was observed among the included studies, with a pooled OR of 3.69 (95% CI 2.74 to 4.96). Heterogeneity and publication bias were not observed in the analysis. Subgroup analyses of the included studies also supported the measure of association of causal links between HPV and OSCC."

Liyanage - BMJ Open 2013 full article / PubMed Central
Liyanage / BMJ Open 2013 full article

Systematic review with meta-analysis: the association between human papillomavirus infection and oesophageal cancer. X Li, C Gao, Y Yang, F Zhou, M Li, Q Jin, L Gao. Aliment Pharmacol Ther 2014 Feb;39(3):270-281. 8990 oesophageal squamous cell carcinoma (SCC) patients and 174 oesophageal adenocarcinomas patients from 76 studies. "Summarised HPV prevalence in oesophageal SCC was 22.2% [95% confidence interval (CI), 18.3-26.7%], HPV-16 was the most frequently observed subtype with a summarised prevalence of 11.4% (95% CI: 8.2-15.7%). With respect to oesophageal adenocarcinoma, HPV prevalence was 35.0% (95% CI, 13.2-65.7%) and HPV-16 prevalence was 11.4% (95% CI: 8.2-15.7%)." Adenocarcinomas were too few to analyze. "Significant association was observed between HPV infection and oesophageal SCC with a summarised odds ratio of 3.32 (95% CI, 2.26-4.87). According to HPV-16, the strength of the association was found to be 3.52 (95% CI, 2.04-6.07)."

Li - Aliment Pharmacol Ther 2014 abstract / PubMed

HPV Infection in Esophageal Squamous Cell Carcinoma and Its Relationship to the Prognosis of Patients in Northern China. F Cao, H Han, F Zhang, B Wang, W Ma, Y Wang, G Sun, M Shi, Y Ren, Y Cheng. ScientificWorldJournal 2014 Jan 12;2014:804738. "HPV was detected in 27.6% (29) of the 105 patients with ESCC, and all positive cases were HPV-16. Twenty-five (86.2%) of the 29 HPV-positive tumors were stained positive for p16. HPV infected patients had better 5-year rates of OS (65.9% versus 43.4% among patients with HPV-negative tumors; P = 0.002 by the log-rank test) and had a 63% reduction in the risk of death (adjusted HR = 0.37, 95% CI = 0.16 to 0.82, and P = 0.01)."

Cao - ScientificWorldJournal 2014 full article / PubMed Central

Human papilloma virus and esophageal squamous cell carcinoma. H Haeri, O Mardani, F Asadi-Amoli, R Shahsiah. Acta Med Iran 2014 Mar;52(3):197-200. None of 30 cases and controls were positive for HPV L1 gene.

Haeri - Acta Med Iran 2014 abstract / PubMed

A case-control study of the role of human papillomavirus in oesophageal squamous cell carcinoma in australia. SS Liyanage, E Segelov, A Malik, SM Garland, SN Tabrizi, E Cummins, H Seale, B Rahman, A Moa, AP Barbour, PJ Crowe, CR MacIntyre. J Oncol 2014;2014:236482. 1/99 cases and 0/100 controls were positive for HPV 16 L1. Combined with another Australian study, 9/321 cases and 0/155 controls were positive, and "The pooled odds ratio for HPV being a risk factor for OSCC was 9.35 (95% CI: 0.47-190.33)."

Liyanage - J Oncol 2014 full article / PubMed Central

Prevalence of human papillomavirus among oesophageal squamous cell carcinoma cases: systematic review and meta-analysis. JL Petrick, AB Wyss, AM Butler, C Cummings, X Sun, C Poole, JS Smith, AF Olshan. Br J Cancer 2014 Apr 29;110(9):2369-2377. 124 studies with a total of 13 832 OSCC cases. "The average HPV prevalence (95% confidence interval) among OSCC cases was 0.277 (0.234, 0.320) by polymerase chain reaction; 0.243 (0.159, 0.326) by in situ hybridisation; 0.304 (0.185, 0.423) by immunohistochemistry; 0.322 (0.154, 0.490) by L1 serology; and 0.176 (0.061, 0.292) by Southern/slot/dot blot. The highest HPV prevalence was found in Africa and Asia, notably among Chinese studies from provinces with high OSCC incidence rates."

Petrick - Br J Cancer 2014 abstract / PubMed

Prevalence of human papillomavirus infection in esophageal and cervical cancers in the high incidence area for the two diseases from 2007 to 2009 in Linzhou of Henan Province, Northern China. HY Liu, SL Zhou, JW Ku, DY Zhang, B Li, XN Han, ZM Fan, JL Cui, HL Lin, ET Guo, X Chen, Y Yuan, JJ Han, W Zhang, LQ Zhang, FY Zhou, SX Liao, JY Hong, LD Wang. Arch Virol 2014 Jun;159(6):1393-1401. 145 frozen esophageal tissues, including 30 normal epithelium, 37 dysplasias and 78 invasive squamous cell carcinoma. 22% of normal, 70% of dysplasia, and 69% of invasive ESCCs were positive for HPV. "Infection with the high-risk HPV types increased the risk for both DYS and ESCC by 4-fold (DYS vs. ENOR: OR = 4.73, 95 %CI = 1.68-13.32; ESCC vs. ENOR: OR = 4.50, 95 %CI = 1.83-11.05)..."

Liu - Arch Virol 2014 abstract / PubMed

Association between human papillomavirus (HPV) and oesophageal squamous cell carcinoma: a meta-analysis. HA Hardefeldt, MR Cox, GD Eslick. Epidemiol Infect 2014 Jun;142(6):1119-1137. 132 studies. "There was evidence of an increased risk of OSCC in patients with HPV infection [odds ratio (OR) 2·69, 95% confidence interval (CI) 2·05-3·54]. The prevalence of HPV in OSCC was found to be 24·8%. There was an increased risk associated with HPV-16 infection (OR 2·35, 95% CI 1·73-3·19). Subgroup analyses showed geographical variance, with Asia (OR 2·94, 95% CI 2·16-4·00), and particularly China (OR 2·85, 95% CI 2·05-3·96) being high-risk areas."

Hardefeldt - Epidemiol Infect 2014 abstract / PubMed

The absence of human papillomavirus in esophageal squamous cell carcinoma in East China. H Teng, X Li, X Liu, J Wu, J Zhang. Int J Clin Exp Pathol 2014 Jun 15;7(7):4184-4193. 177 tumor samples. "The genotyping results showed that only six samples were weakly positive for HPV: two for HPV16, two for HPV11 and two for HPV35, with no samples showing strong positive signals. The IHC results showed only five samples with diffuse positive staining, with the other samples being completely negative or having only focal positive signals, which were considered as negative."

Teng - Int J Clin Exp Pathol 2014 full article / PubMed Central

Prognostic significance of high-risk human papillomavirus and p16INK4A in patients with esophageal squamous cell carcinoma. F Cao, W Zhang, F Zhang, H Han, J Xu, Y Cheng. Int J Clin Exp Med 2014 Oct 15;7(10):3430-3438. 29/105 (27.6%) consecutive ESCCs were positive for HPV. "P16 was detected in 25 of the 29 patients (86.2%) who were HPV-positive, and only 14 of 76 patients (18.4%) who were HPV-negative (P < 0.001)."

Cao - Int J Clin Exp Med 2014 full article / PubMed Central

Incidence and prognostic impact of high-risk HPV tumor infection in cervical esophageal carcinoma. EB Ludmir, M Palta, X Zhang, Y Wu, CG Willett, BG Czito. J Gastrointest Oncol 2014 Dec;5(6):401-407. 1/19 (5.3%) tumor samples were positive for HPV.

Ludmir - J Gastrointest Oncol 2014 full article / PubMed Central

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."

Shen - Int J Mol Med 2001 abstract / PubMed

[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."

Liu - Zhonghua Liu Xing Bing Xue Za Zhi 2007 abstract / PubMed

Human papillomavirus DNA and P16(INK4A) expression in concurrent esophageal and gastric cardia cancers. GC Ding, JL Ren, FB Chang, JL Li, L Yuan, X Song, SL Zhou, T Guo, ZM Fan, Y Zeng, LD Wang. World J Gastroenterol 2010 Dec 14;16(46):5901-5906. "Among the CC [concurrent esophagus and gastric cardia cancer] specimens, HPV16-DNA was found in eight cases of esophageal squamous cell carcinoma (ESCC) and five cases of gastric cardia adenocarcinoma (GCA), respectively (47% vs 29%), and two of both ESCC and GCA. P16(INK4A) was highly expressed in both ESCC and GCA. In the HPV-associated positive CC, higher P16(INK4A) expression was observed in the GCA than in the ESCC (75% vs 25%, P < 0.05)."

Ding - World J Gastroenterol 2010 abstract / PubMed

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 the 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."

Islami - Int J Epidemiol 2009 abstract / PubMed

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."

Del Valle - Cancer 2005 abstract / PubMed

See also:

HPV Causes Oral Cancer
HPV Strains and Oncogenicity
HPV is implicated in laryngeal cancer
HPV Causes Head and Neck Cancer
JC Polyoma Virus Causes Colon Cancer

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.

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cast 12-11-14