Commentary - Journal of Cancer Immunology (2020) Volume 2, Issue 2
Verrucous Carcinoma of the Esophagus: Its Unique Etiology and Association with Human Papilloma Virus
Satoshi Tabuchi1, Kazuo Koyanagi2*, Soji Ozawa2, Shigeyuki Kawachi1
Department of Digestive and Transplantation Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Tokyo, 193-0998, Japan
Department of Gastroenterological Surgery, Tokai University School of Medicine, Isehara, Kanagawa, 259-1193, Japan
- *Corresponding Author:
- Kazuo Koyanagi
Received date: May 02, 2020; Accepted date: May 14, 2020
Citation: Tabuchi S, Koyanagi K, Ozawa S, Kawachi S. Verrucous Carcinoma of the Esophagus: Its Unique Etiology and Association with Human Papilloma Virus. J Cancer Immunol. 2(2): 44-51.
Copyright: © 2020 Tabuchi S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Verrucous carcinoma of the esophagus (VCE) is a rare variant of esophageal squamous cell carcinoma. Most cases of VCE presents as an exophytic, slow-growing mass with a superficial growth pattern. Even when VCE exhibits a characteristic pattern during an endoscopic examination, it is very difficult to make a definitive diagnosis of VCE preoperatively, because biopsy specimens are only characterized by nonspecific acanthosis and hyperkeratosis or parakeratosis associated with inflammation. As well as the characteristics of VCE, the etiology of the disease is even unique. VCE is typically associated with chronic mucosal irritation such as reflux esophagitis, achalasia, and lye ingestion that has resulted in esophageal inflammation or a long-term local disease process in addition to the classic risk factors of nicotine and alcohol consumption. Recent studies had indicated that human papilloma virus (HPV) infection might be associated with VCE. While HPV may be related to VCE initiation, involvement of HPV in the etiology of VCE requires further investigation. VCE’s etiology and therapeutic strategy, including the vaccination against HPV, should be established.
Verrucous carcinoma, Esophagus, Human papilloma virus
Verrucous carcinoma is an extremely rare disease, and it is unique in terms of its appearance, growth pattern, and etiology. In 1948, Ackerman first described verrucous squamous cell carcinoma (VSC) as a variant of oral squamous cell carcinoma , and he collected 31 cases of oral neoplasms under the name, “Verrucous Carcinoma of the Oral Cavity.” VSC was described as having the following characteristics: slow growing, well-differentiated, irregular surface appearance with a propensity to spread locally, and VSC has subsequently been reported in the mouth, nasal cavity, larynx, glans penis, scrotum, vulva, vagina, cervix, endometrium, urinary bladder, and anorectal region. Verrucous carcinoma of the esophagus (VCE) is a rare variant of esophageal squamous cell carcinoma. In 1967, Minielly et al. described VCE for the first time in a series of five cases . Interestingly, there are reports suggesting an association between VCE and human papilloma virus (HPV) infection, stating that HPV may be involved in the carcinogenesis of VCE. Although VCE exhibits the same typical appearance and growth patterns as VSC in other organs, because of the paucity of cases neither its etiology nor therapeutic strategies have not been well assessed. In this commentary we reviewed previous reports and discussed VCE, in particular association between its etiology and HPV infection.
Review of the Literature Concerning VCE
We used the keywords “esophagus” and “verrucous carcinoma” to search the literature in the PubMed database during the period from 1983 to 2018 (Table 1). Only 48 cases of VCE (including our case) have been described since Minielly’s first report of VCE . Males have predominated, but the proportion of women with VCE (28 males, 18 females, 2 gender unknown) has been higher among esophageal squamous cell carcinoma patients. The male-female ratio is about 3:2, and VCE patients’ ages (median, 64 years; range, 36-79 years) have been similar to those of esophageal squamous cell carcinoma patients. The most common chief complaint was dysphagia (in 39 (85%) of the 46 cases). The tumors have predominantly been located in the lower third of the esophagus (30 cases, 64%), and their frequent location in the lower-third of the esophagus may be associated with chronic esophageal mucosal inflammation. Almost all patients had a medical history that resulted in esophageal injury or inflammation before the diagnosis of VCE: 90% of the patients have had an associated chronic disease or condition (e.g., achalasia, reflux esophagitis, candida esophagitis, and heavy consumption of nicotine and alcohol).
|No||Author||Year||Age/Sex||Chief complaint||Past history||Location||1st diagnosis||Tumor size (cm)||Treatment||Prognosis||T||N||M |
|1||Minielly2)||1967||58/M||dysphagia||achalasia||upper||benign||9×8.5||OPE||1m, dead||3||0||0 |
|2|| ||1967||70/F||dysphagia||diverticulum||upper||VC||large tumor||RT||unknown||N/A||N/A||N/A |
|3|| ||1967||70/F||dysphagia||achalasia||upper||VC||large tumor||RT||2m, dead||4||N/A||N/A |
|4|| ||1967||36/M||dysphagia||diverticulum||lower||SCC||9×8||OPE||2m, dead||4||?||N/A |
|5|| ||1967||57/M||dysphagia||none||lower||benign||N/A||BSC||5m, dead||N/A||N/A||N/A |
|6||Parkinson26)||1970||76/M||melena||obstruction||middle||SCC||7.5||BSC||1m, dead||1b||0||0 |
|7||Meyerowitz27)||1971||45/M||hematemesis||none||lower||benign||8×5.5||OPE, RT||9m, dead||2||N/A||0 |
|8||Sridher28)||1980||54/M||dysphagia||hiatal hernia||lower||benign||2||OPE||unknown||1b||0||N/A |
|9||Sakurai16)||1983||78/M||dysphagia||none||upper||VC||10×5||CT||6m, alive||4||N/A||N/A |
|10||Agha29)||1984||66/M||dysphagia||acid burn||upper||VC||large tumor||BSC||2m, dead||4||N/A||N/A|
|11||Barbier30)||1987||50/F||dysphagia||hiatal hernia||lower||VC||N/A||OPE||10m, alive||1a||0||0|
|12||Koerfgen31)||1988||75/M||dysphagia||traumatic stenosis||lower||benign||N/A||OPE||36m, alive||2||0||0|
|13|| ||1988||54/?||dysphagia||none||lower||benign||6.5×6.5||OPE||18m, alive||2||0||0|
|15||Biemond13)||1991||76/F||dysphagia, dyspnea||RE||middle||benign||15||BSC||1m, dead||4||0||0|
|23||Devlin8)||2004||56/F||abdominal pain||none||lower||benign||2.7||OPE||14m, alive||1b||0||0|
|25||Liberale21)||2005||41/M||chest pain||none||lower||VC||N/A||Antiviral Tx||6m, dead||4||N/A||N/A|
|33||Sweetser3)||2014||61/M||dysphagia||N/A||extensive||N/A||N/A||OPE, CRT||72m, alive||2||0||0|
|34|| ||2014||73/F||dysphagia||N/A||lower||N/A||N/A||CRT||36m, alive||N/A||N/A||N/A|
|35|| ||2014||66/M||dysphagia||N/A||lower||N/A||N/A||OPE||120m, alive||1||0||0|
|36|| ||2014||70/F||dysphagia||N/A||extensive||N/A||N/A||OPE||6m, dead||1||0||0|
|37|| ||2014||71/M||dysphagia||N/A||middle||N/A||N/A||N/A||36m, dead||2||0||0|
|40|| ||2014||62/M||dysphagia||N/A||extensive||N/A||N/A||OPE||96m, alive||3||0||0|
|41|| ||2014||63/F||dysphagia||N/A||extensive||N/A||N/A||CRT||12m, alive||3||0||0|
|42|| ||2014||68/M||dysphagia||N/A||extensive||N/A||N/A||OPE, CRT||24m, alive||1||0||0|
|43|| ||2014||62/F||dysphagia||N/A||middle||N/A||N/A||OPE||24m, alive||1||0||0|
|46||Hoffmann43)||2018||61/M||dysphagia||systemic sclerosis||lower||VC||N/A||OPE||24m, alive||1b||0||0|
|47|| ||2018||52/F||dysphagia||none||lower||VC||10||OPE||24m, alive||2||0||0|
VC: Verrucous carcinoma; SCC: Squamous cell carcinoma; OPE: Operation; CRT: Chemoradiation; CT: Chemotherapy; RT: Irradiation; EMR: Endoscopic mucosal resection; ESD: Endoscopic submucosal dissection; Antiviral Tx: Antiviral treatment; BSC: Best supportive care; RE: Reflux esophagitis; N/A not assessed
Table 1: Reported cases of Verrucous carcinoma of esophagus.
VCE tumor sizes have been relatively large, but depth of invasion has generally been shallow. In 23 (48% of the 48 cases reported) of the 29 cases in which tumor size was recorded, the tumor measured 5 cm or more in diameter. Tumor invasion has been limited to the muscle layer (T1 and T2): in 68% of the patients in which depth of tumor invasion was recorded, but in seven cases (17%) the tumor was locally advanced (T4). This could be explained by the difficulty of making the diagnosis of VCE. In addition, very low incidence of lymph node metastasis (8%) and distant organ metastasis (0%) have been special characteristics of VCE.
The histopathologic features of VCE include good preservation of the epithelial basement membrane and highly differentiated histology, both of which are important in differentiating VCE from other esophageal carcinomas. However, in the majority of cases, mucosal biopsies were diagnosed as acanthosis, hyperkeratosis, and parakeratosis, and these nonspecific pathological findings make the correct diagnosis of VCE difficult and delay the start of treatment. Using EUS may provide information that is crucial to the diagnostic process . The majority of VCE patients have impressive inflammatory changes that extend deep into the submucosal space and the muscularis propria, and EUS is ideally suited to detecting such changes. Since distorted architecture and local invasion are readily visible by EUS, EUS may make it possible to establish the appropriate diagnosis of VCE.
The histological picture of VCE resembles that of benign squamous cell papilloma. However, VCE tends to be deep-growing and invasive, whereas papilloma tends to grow superficially. Biemond et al.  proposed that the presence of infiltration is essential to differentiating VCE from squamous papilloma. It should be noted that some squamous papilloma shows evidence of dysplasia without infiltration. However, because of the limited low-grade nevus cell nest formation and the highly keratinized surface of the tumors, it is not easy to diagnose VCE on the basis of the findings in preoperative biopsy samples. In fact, only 12 (25%) of the 48 cases were diagnosed as esophageal VC based on the biopsy pathology findings. As Oh et al. have reported, endoscopic mucosal resection (EMR) might be a useful means of making an accurate diagnosis in suspected cases of VCE .
Treatment consisted of surgery in 28 cases, chemoradiation therapy in 5 cases, radiotherapy in 3 cases, chemotherapy in 1 case, and best supportive care in 8 cases. Before 1990, all patients had undergone esophageal resection and experienced significant postoperative complications. Surgical treatment after 1990 yielded favorable results because of improvements in surgical procedures and perioperative management in recent years as well as because of the low malignant potentials of VCE. The effectiveness of radiotherapy and chemotherapy, on the other hand, has been very limited . Chemotherapeutic regimens that have been used to treat squamous cell carcinoma have not been effective against VCE. There has been only one report of partial treatment response with bleomycin , and new drugs or regimens need to be developed. If a locally advanced tumor stage is the initial diagnosis and surgery is technically possible, esophageal resection should be considered because of the rarity of lymph node metastases and the limited chemo- and radio-sensitivity of VCE.
Association between VCE and Esophageal Mucosal Inflammation
In addition to the classic risk factors of nicotine and alcohol consumption, VCE is typically associated with chronic esophageal mucosal inflammation. Kavin et al.  reported a case of VCE in a patient who had chronic esophagitis secondary to a caustic injury as a result of ingesting aerosolized lye and kerosene syrup. After 16 years of serial endoscopic surveillance, a verrucous mass was detected in the distal esophagus, and serial biopsies showed progression from esophagitis to leukoplakia, then to papillary hyperplasia and, finally, to dysplasia. Similar findings had been reported in laboratory rats in which VCE was experimentally induced by prolonged exposure of the esophagus to N-methyl-N-nitrosoaniline . The lesions observed in the rats progressed in stages from acanthosis and hyperkeratosis, to leukoplakia, and then to papillary hypertrophy, and within 500 days the esophageal surface transformed from its normal smooth appearance to having a verrucous exophytic appearance. We also described that candida esophagitis was diagnosed during long-term follow-up period and might be related to the VCE . Thus, esophageal injury or irritation is likely to be a prerequisite for the sequential development of dysplastic changes over time.
Association between VCE and Human Papilloma Virus Infection
HPV infection accounts for approximately more than 5% of the worldwide human cancers . HPV can infect the stratified epithelia of the skin or mucous membranes of the upper gastrointestinal, respiratory, or anogenital tract, potentially leading to the outcomes such as genital warts and laryngeal papilloma, and sometimes certain cancers. Various types of HPV have been associated with developing cancers in several organs: “low risk” and “high risk” depending on the oncological potential. VSC is uniquely suspected of being related to HPV. HPV infection has been reported to be associated with several cancers, and involvement of HPV in head and neck cancers, particularly oropharyngeal cancer, has recently become clear and been attracting attention. HPV infection due to sexual activity is the cause, and the HPV-positive rate in head and neck cancer patients has been increasing every year . Developing the cancerous lesion after HPV infection may be associated with the immune status of the patients. De Socio et al. has reported a case of HPVassociated lips verrucous carcinoma in HIV-infected male patient . HIV-positive patients have a 2 to 3 times higher prevalence of oral HPV infection than HIVnegative patients. It has also become clearer that HPV infection is the cause of almost all cases of cervical cancer, and HPV vaccination has been introduced worldwide as a means of preventing cervical cancer . HPV may be involved in carcinogenesis . HPV infection causes high expression of oncogenes E6 and E7 in basal cells, promotes proteolysis of tumor suppressor genes p53 and Rb, and inactivates their functions.
There have also been a number of reports of HPV being related to primary laryngeal VC . Also, many studies have addressed a possible association between HPV infection and esophageal dysplasia. Tornesello et al. reported 66 esophageal cancer patients and demonstrated the relatively higher prevalence of HPV infection in welldifferentiated squamous cell carcinoma, suggesting a tropism of HPV replication in keratinized tissues . Several investigators have clearly demonstrated the positive association between HPV and VCE [18,19]. There are many HPV genotypes, and genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 are considered to be a high-risk group . Yong et al. reported associations between HPV type 16 and 18 infection and esophageal squamous cell carcinoma , and Vieira et al. have demonstrated HPV type 11 infection in endoscopic biopsy specimens of VCE . Tonna et al. detected HPV type 51 deoxyribonucleic acid (DNA) in endoscopic biopsy specimens of VCE by performing polymerase chain reactions, and they stated that the presence of HPV DNA in the endoscopic biopsies raised the possibility that HPV infection underlies the hyperkeratosis and malignant transformation . Liberale et al.  reported a case of HPV-positive VCE with esophagobronchial fistula in a 41-year-old man, initially responded to antiviral treatment.
Cappellesso et al. , on the other hand, have reported that HPV infection may not be involved in VCE, but, unlike Vieira et al. and Tonna et al., they tested surgically resected specimens for HPV infection by performing chromogenic hybridization. These different findings might be explained by destruction of HPV DNA in the formalin fixed paraffin embedded (FFPE) tissues of resected specimens, or HPV may have played an initiating role and no longer have been involved once the lesion underwent malignant transformation.
Until recently, no data have been available on the efficacy of the HPV vaccines in preventing HPV infections and its related cancers. However, nowadays, it is well known that vaccination against HPV during childhood and prior to HPV exposure can prevent HPV-associated cervical cancers later in their adult lives. Accordingly, it could be proposed to administer HPV vaccine against VSC including VCE to prevent the acceleration of malignant progression. We should investigate the association between VCE and HPV infection further to understand and successfully treat this disease.
VCE is a rare, well differentiated carcinoma that is slow growing and invades locally. VCE is difficult to diagnose, because histologic examination of mucosal biopsy specimens usually shows only nonspecific inflammatory changes. If VCE is suspected based on the history and clinical findings, we strongly recommend esophagectomy, because distant and lymph node metastasis are relatively rare. HPV may be involved in VCE initiation, and the possible etiological involvement of HPV should be investigated.
Conflicts of Interest
The authors declare that they have no conflicts of interest.
- Ackerman LV. Verrucous carcinoma of the oral cavity.Surgery. 1948 Apr 1;23(4):670-8.
- Minielly JA, Harrison Jr EG, Fontana RS, Payne WS. Verrucous squamous cell carcinoma of the esophagus. Cancer. 1967 Dec;20(12):2078-87.
- Devlin S, Falck V, Urbanski SJ, Mitchell P, Romagnuolo J. Verrucous Carcinoma of the Esophagus Eluding Multiple Sets of Endoscopic Biopsies and Endoscopic Ultrasound: A Case Report and Review of the Literarure. Canadian Journal of Gastroenterology and Hepatology. 2004;18(7):459-62.
- Biemond P, ten Kate FJ, van Blankenstein M. Esophageal verrucous carcinoma: histologically a lowgrade malignancy but clinically a fatal disease. Journal of Clinical Gastroenterology. 1991 Feb 1;13(1):102-7.
- Oh K, Nishigami T, Takubo K, Shimada Y, Fujimoto J. A case of verrucous squamous cell carcinoma of the esophagus. Esophagus. 2009 Dec 1;6(4):263.
- Ferlito A, Rinaldo A, Mannarà GM. Is primary radiotherapy an appropriate option for the treatment of verrucous carcinoma of the head and neck?. The Journal of Laryngology & Otology. 1998 Feb;112(2):132-9.
- Sakurai TO, Fuchigami TA, Omae T, Iwashita A, Kume K, Asano S. Bleomycin in verrucous squamous cell carcinoma of the oesophagus. Postgraduate Medical Journal. 1983 Sep 1;59(695):578-80.
- Kavin HY, Yaremko LI, Valaitis JO, Chowdhury LO.Chronic esophagitis evolving to verrucous squamous cell carcinoma: possible role of exogenous chemical carcinogens. Gastroenterology. 1996 Mar 1;110(3):904-14.
- Napalkov NP, Pozharisski KM. Morphogenesis of experimental tumors of the esophagus. Journal of the National Cancer Institute. 1969 Jun 1;42(6):927-40.
- Tabuchi S, Koyanagi K, Nagata K, Ozawa S, Kawachi S. Verrucous carcinoma of the esophagus: a case report and literature review. Surgical Case Reports. 2020 Feb 1;6(1):35.
- Chung CH, Bagheri A, D’Souza G. Epidemiology of oral human papillomavirus infection. Oral Oncology. 2014 May 1;50(5):364-9.
- Maruyama H, Yasui T, Ishikawa-Fujiwara T, Morii E, Yamamoto Y, Yoshii T, Takenaka Y, Nakahara S, Todo T, Hongyo T, Inohara H. Human papillomavirus and p53 mutations in head and neck squamous cell carcinoma among Japanese population. Cancer Science. 2014 Apr;105(4):409-17.
- De Socio GV, Bidovanets O, Tomassini GM, Fanelli L, Simonetti S. Human Papilloma Virus–Associated Lips Verrucous Carcinoma in HIV-Infected Male. Journal of the International Association of Providers of AIDS Care (JIAPAC). 2017 Jul;16(4):324-6.
- Zur Hausen H. Papillomavirus and cancer from basic studies to clinical application. Nat. Rev. Cancer 2 (5): 342-50.
- Chung CH, Gillison ML. Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications. Clinical Cancer Research. 2009 Nov 15;15(22):6758-62.
- Abramson AL, Brandsma J, Steinberg B, Winkler B. Verrucous carcinoma of the larynx: possible human papillomavirus etiology. Archives of Otolaryngology. 1985 Nov 1;111(11):709-15.
- Tornesello ML, Monaco R, Nappi O, Buonaguro L, Buonaguro FM. Detection of mucosal and cutaneous human papillomaviruses in oesophagitis, squamous cell carcinoma and adenocarcinoma of the oesophagus. Journal of Clinical Virology. 2009 May 1;45(1):28-33.
- Liberale G, De Simone P, Snoeck R, Feron P, Gelin M, El Nakadi I. Verrucous carcinoma of the esophagus. A case report. Minerva Chirurgica. 2005; 60 (1): 61-5.
- Tonna J, Palefsky JM, Rabban J, Campos GM, Theodore P, Ladabaum U. Esophageal verrucous carcinoma arising from hyperkeratotic plaques associated with human papilloma virus type 51. Diseases of the Esophagus. 2010 Jul 1;23(5):E17-20.
- Cappellesso R, Coati I, Barzon L, Peta E, Masi G, Scarpa M, et al. Human papillomavirus infection is not involved in esophageal verrucous carcinoma. Human Pathology. 2019 Mar 1;85:50-7.
- Yong F, Xudong N, Lijie T. Human papillomavirus types 16 and 18 in esophagus squamous cell carcinoma:a meta-analysis. Annals of Epidemiology. 2013 Nov 1;23(11):726-34.
- Vieira CL, Lopes JC, Velosa J. A case of esophageal squamous cell carcinoma with positive HPV 11. Gastroenterologia y Hepatologia. 2013 May 1;36(5):311-5.
- Parkinson AT, Haidak GL, McInerney RP. Verrucous squamous cell carcinoma of the esophagus following lye stricture. Chest. 1970 May 1;57(5):489-92.
- Meyerowitz BR, Shea LT. The natural history of squamous verrucose carcinoma of the esophagus. The Journal of Thoracic and Cardiovascular Surgery. 1971 Apr 1;61(4):646-9.
- Sridhar C, Zeskind HJ, Rising JA. Verrucous squamous-cell carcinoma: an unusual tumor of the esophagus. Radiology. 1980 Sep;136(3):614.
- Agha FP, Weatherbee L, Sams JS. Verrucous carcinoma of the esophagus. American Journal of Gastroenterology. 1984;79(11):844-9.
- Barbier PA, Luder PJ, Wagner HE, Becker CD, Scheurer U, Ruchti C. Verrucous acanthosis--so-called verrucous carcinoma--of the esophagus. Zeitschrift fur Gastroenterologie. 1987 Feb;25(2):93-7.
- Koerfgen HP, Husemann B, Giedl J, Hohenberger W. Verrucous carcinoma of the esophagus. Endoscopy. 1988 Nov;20(06):326-9.
- Jasim KA, Bateson MC. Verrucous carcinoma of the oesophagus—a diagnostic problem. Histopathology. 1990 Nov;17(5):473-5.
- Roach E, Barr G. Verrucous carcinoma of the oesophagus and achalasia. Journal of Gastroenterology and Hepatology. 1993 Feb;8(1):107-9.
- Garrard CL, Sheih WJ, Cohn RA, Sawyers JL.Verrucous carcinoma of the esophagus: surgical treatment for an often fatal disease. The American Surgeon. 1994 Aug;60(8):613-6.
- Malik AB, Bidani JA, Rich HG, McCully KS. Longterm survival in a patient with verrucous carcinoma of the esophagus. American Journal of Gastroenterology. 1996 May 1;91(5).
- Tajiri H, Muto M, Boku N, Ohtsu A, Yoshida S, Kawahara H. Verrucous carcinoma of the esophagus completely resected by endoscopy. The American Journal of Gastroenterology. 2000 Apr 1;95(4):1076-7.
- Eren?o C, Lopez JI, Loizate A, Bilbao FJ. Verrucous carcinoma of the esophagus. Endoscopy. 2001; 33 (3): 297.
- Osborn NK, KEATE R, Trastek VF, Nguyen CC. Verrucous carcinoma of the esophagus. Digestive Diseases and Sciences. 2003 Mar 1;48(3):465.
- Pfitzmann R, Abou-Rebyeh H, Krenn V, Settmacher U, Neuhaus P. Verrucous carcinoma of the esophagus-a rare entity. Zentralblatt fur Chirurgie. 2004 Jan;129(1):70-2.
- Na S, Choi KD, Yoo C, Chang Y, Song HJ, Lee GH, et al. Verrucous carcinoma of the esophagus. Gastrointestinal Endoscopy. 2009 Oct;70(4):803-6.
- Macias-Garcia F, Martinez-Lesquereux L, Fernandez B, Parada P, Larino-Noia J, Sobrino-Faya M, et al. Verrucous carcinoma of the esophagus: a complex diagnosis. Endoscopy. 2010 Dec;42(S 02):E137-8.
- Munson GW, Romero Y, Francis DL. Verrucous squamous cell carcinoma: a rare esophageal malignancy. Clinical Gastroenterology and Hepatology. 2010 Jun 1;8(6):A20.
- Taniyama Y, Fujishima F, Takubo K, Sakurai T, Okamoto H, Nakano T, et al. A case of verrucous carcinoma of the esophagus associated with difficult histopathological diagnosis of endoscopic biopsy specimens. Esophagus. 2012 Dec 1;9(4):223-7.
- Sweetser S, Jacobs NL, Wong Kee Song LM. Endoscopic diagnosis and treatment of esophageal verrucous squamous cell cancer. Diseases of the Esophagus. 2014 Jul 1;27(5):452-6.
- Abe T, Kato M, Itagaki M, Hamatani S, Kawahara Y, Ito S, et al. Endoscopic submucosal dissection for an atypical small verrucous carcinoma: a case report. Journal of Medical Case Reports. 2016 Dec 1;10(1):74.
- Cox R, Welch C, Cameron D, Roche E. Gastrointestinal: Verrucous cell carcinoma (VCC) of the esophagus: A rare variant of esophageal squamous cell carcinoma (SCC). Journal of Gastroenterology and Hepatology. 2017 Mar;32(3):544.
- Hoffmann R, Hebenstreit A, Game PA, Ruszkiewicz AR, Thompson SK. Verrucous carcinoma of the oesophagus. ANZ Journal of Surgery. 2018 Nov;88(11):E797-8.