Verrucous Carcinoma

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Verrucous carcinoma is a relatively uncommon, locally aggressive, clinically exophytic, low-grade, slow-growing, well-differentiated squamous cell carcinoma with minimal metastatic potential.

Verrucous carcinoma may involve the oral cavity, larynx, anogenital region, plantar surface of the foot, and, less commonly, other cutaneous sites. See the image below.

In 1948, Ackerman first described verrucous carcinoma in the oral cavity as a low-grade tumor that generally is considered a clinicopathologic variant of squamous cell carcinoma. ^[1] Aird et al first described cutaneous verrucous carcinoma (carcinoma cuniculatum) in 1954, and it was named as such because of its characteristic cryptlike spaces on histology. ^[2]

The pathogenesis of verrucous carcinoma is not yet fully elucidated. ^[3] Leading theories include human papillomavirus (HPV) infection (oral cavity, anogenital region, plantar foot, and a small subset of cutaneous verrucous carcinoma), ^[4] chemical carcinogenesis induced by smoking and chewing tobacco, ^[5] alcohol consumption and betel nut chewing (oral lesions), and chronic inflammation. Schistosomiasis is associated with verrucous carcinoma of the bladder. ^[6]

HPV may play a role in the development of verrucous carcinoma. HPV types 6 and 11 are most frequently associated with the Buschke-Löwenstein tumor. ^[7] In plantar lesions, HPV type 16 has been reported. ^[8] Finally, HPV type 33 has been reported in a verrucous carcinoma of the scalp. ^[4]

Despite the presence of HPV strains within some lesions of verrucous carcinoma, a causal relationship has not been proven and remains controversial. ^{[9, 10]}

Inflammation appears to sometimes play a role in the development of verrucous carcinoma. For instance, cutaneous verrucous carcinoma may develop at sites of inflammation or scarring such as decubitus ulcers or areas affected by hidradenitis suppurativa. ^{[7, 11]} In addition, lichen sclerosus may predispose patients to the development of penile verrucous carcinomas. ^[12] Similarly, verrucous carcinomas of the oral cavity have been reported to develop in patients with long-standing oral ulcerative lichen planus and chronic candidiasis.

Associations in oral verrucous carcinoma have been found in patients who chewed or inhaled tobacco and betel nuts, dipped snuff, and/or consumed alcohol. Lesions developed at the sites where tobacco was habitually placed in the mouth. ^[13]

Furthermore, oral verrucous carcinoma is associated with poor dental hygiene, ill-fitting dentures, and low socioeconomic status. Oral verrucous carcinoma has a higher incidence in males and in immunocompromised patients. ^[13]

Schistosomal infection often is coexistent with verrucous carcinoma of the bladder. ^[6]

The incidence of verrucous carcinoma in the United States and worldwide is unknown. ^[14]

Verrucous carcinoma is reported predominantly in whites.

Verrucous carcinoma primarily affects men.

Verrucous carcinoma generally occurs in middle-aged (50s) patients ^[14] ; however, the anogenital type of verrucous carcinoma has been reported to develop in men aged 18-86 years. ^[7]

Overall, patients with verrucous carcinoma have a favorable prognosis, although the course of verrucous carcinoma lesions is characterized by slow, continuous, local growth. Morbidity results from local skin and soft-tissue destruction and, occasionally, from perineural, muscle, and even bone invasion. The development of distant metastases is rare. Verrucous carcinoma mortality usually is due to local invasion rather than metastatic spread.

In most cases of verrucous carcinomas, regardless of the variant, the clinical outcome is rarely an aggressive course. Local verrucous carcinoma recurrence following definitive treatment is not uncommon. Regarding oral verrucous carcinoma, the reported recurrence rate ranges from 6-40%. If metastasis does occur, it is mainly at the regional lymph nodes. ^[13] There have been reports of metastases in distant sites, but this is considered rare. In long-standing lesions, occasional destruction of adjustment structures such as cartilage, tendons, and bones can occur. Patients with oral verrucous carcinoma may be at an increased risk of a second primary oral squamous cell carcinoma, which carries a poor prognosis.

Advise patients about the importance of receiving effective treatment for areas of chronic skin inflammation or trauma (eg, leg or decubitus ulcers) to prevent these problems from developing malignancies within them. Improved oral, genital, and perianal hygiene may help to prevent inflammatory conditions that predispose patients to verrucous carcinoma. Cessation of chewing tobacco use may help to prevent oral verrucous carcinoma.

For patient education resources, see the Cancer and Tumors Center and Warts Center, as well as Skin Cancer, Warts, and Skin Biopsy.

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Jennifer Shuley Ruth, MD Resident Physician, Department of Dermatology, Baylor College of Medicine

Jennifer Shuley Ruth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society for Dermatologic Surgery, Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Mohsin R Mir, MD Director, High Risk Skin Cancer Clinic, Assistant Professor, Mohs Surgery, Laser and Cosmetic Surgery, Department of Dermatology, Baylor College of Medicine

Mohsin R Mir, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

John G Albertini, MD Private Practice, The Skin Surgery Center; Clinical Associate Professor (Volunteer), Department of Plastic and Reconstructive Surgery, Wake Forest University School of Medicine; President-Elect, American College of Mohs Surgery

John G Albertini, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: QualDerm Partners; Novascan<br/>Have a 5% or greater equity interest in: QualDerm Partners – North Carolina.

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.

Kelly M Cordoro, MD Assistant Professor of Clinical Dermatology and Pediatrics, Department of Dermatology, University of California, San Francisco School of Medicine

Kelly M Cordoro, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Medical Society of Virginia, Society for Pediatric Dermatology, Women’s Dermatologic Society, Association of Professors of Dermatology, National Psoriasis Foundation, Dermatology Foundation

Disclosure: Nothing to disclose.

Mohsin Ali, MBBS, FRCP, MRCP, MRCPI, Consulting Staff, Department of Dermatology, Amersham General Hospital, UK

Disclosure: Nothing to disclose.

Sohail Mansoor, MBBS, MSc Dermatologist and Lead Physician in Dermatologic Surgery, Department of Dermatology, Barnet Hospital, UK

Sohail Mansoor, MBBS, MSc is a member of the following medical societies: American Academy of Anti-Aging Medicine, American Academy of Dermatology, American Society for Dermatologic Surgery, Royal College of Physicians and Surgeons of Glasgow, and Royal College of Physicians of the United Kingdom

Disclosure: Nothing to disclose.

Nicole Sakka, MBBS Foundation Year 2, Royal Liverpool and Broadgreen University Hospital, Liverpool, UK

Disclosure: Nothing to disclose.

Bassam Zeina, MD, PhD Consulting Staff, Department of Dermatology, Milton Keynes Hospital, UK

Bassam Zeina, MD, PhD is a member of the following medical societies: British Association of Dermatologists, British Medical Association, and Royal Society of Medicine

Disclosure: Nothing to disclose.

Verrucous Carcinoma

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