Head and Neck Cutaneous Squamous Cell Carcinoma Medication

  • Author: Marcus Monroe, MD; Chief Editor: Arlen D Meyers, MD, MBA   more...
 
Updated: Jul 7, 2011
 

Medication Summary

Nonsurgical management for cutaneous squamous cell carcinoma (SCC) includes the use of systemic and topical chemotherapy. Various topical agents are used to treat patients with a history of extensive sun exposure or actinic keratosis and SCC in situ. The addition of chemotherapy to radiotherapy may also be beneficial in improving survival in squamous cell carcinoma of the head and neck but it is associated with adverse effects.

Next

Topical Chemotherapy

Class Summary

Nonsurgical options for the treatment of cutaneous squamous cell carcinoma (SCC) include topical chemotherapy and topical immune response modifiers. The use of topical therapy and photodynamic therapy (PDT) is generally limited to actinic keratoses and in situ lesions.

View full drug information

5-Fluorouracil (Efudex, Carac, Fluoroplex)

 

5-Fluorouracil (5-U) is a classic antimetabolite anticancer drug with a chemical structure similar to endogenous intermediates or building blocks of DNA or RNA synthesis. It inhibits tumor cell growth through at least 3 different mechanisms that ultimately disrupt DNA synthesis or cellular viability. Topical 5-FU is approved for the treatment of multiple actinic or solar keratoses.

View full drug information

Imiquimod (Aldara, Zyclara)

 

Imiquimod is approved by the FDA for the treatment of genital warts, actinic keratoses, and superficial basal cell carcinoma (BCC). Imiquimod is an imidazoquinoline that enhances cell-mediated immune responses via the induction of proinflammatory cytokines; that is, it up-regulates interferon and other cytokines.

View full drug information

Diclofenac (Solaraze)

 

Diclofenac gel is approved by the FDA for the treatment of actinic keratoses. It is applied to lesion areas twice a day for a duration of 60-90 days.

Previous
Next

Systemic Chemotherapy

Class Summary

Multiple chemotherapeutic agents have been used to treat metastatic cutaneous squamous cell carcinoma (SCC). Adaptation of traditional chemotherapeutics to local and regional administration techniques in treating head and neck cancers is being actively pursued to provide higher local concentrations of otherwise systemically toxic drugs.

View full drug information

Cetuximab (Erbitux)

 

Cetuximab is approved for the initial treatment of locally or regionally advanced squamous cell carcinoma of the head and neck (SCCHN). Cetuximab when used alone is indicated for the treatment of patients with recurrent or metastatic SCCHN, for whom prior platinum-based therapy has failed. It is a chimeric immunoglobulin G1 monoclonal antibody that inhibits epidermal growth factor receptor (EGFR) and has been reported as successful in several case reports. EGFR inhibitors are well tolerated with relatively low risks, so they may be considered in cases not amenable to surgery or radiation or as an adjuvant in cases considered to have a high risk of death. Current recommendations are to use cetuximab as an alternative to chemotherapy in patients who cannot tolerate chemotherapy.

View full drug information

Cisplatin

 

Cisplatin has been used in the treatment of squamous cell carcinoma of the head and neck. Although this agent is one of the most successful in the treatment of cancer, it produces major toxicities to normal cells and organs at the concentrations necessary for effective treatment of malignancies.

Combination chemoradiotherapy with cisplatin and concurrent radiation therapy has improved locoregional control in locally advanced SCC. Chemoradiotherapy is now considered the standard of care in locally advanced disease following surgical resection and in unresectable disease. Cisplatin-based combination chemotherapy with 5-fluorouracil (5-FU), methotrexate, bleomycin, and doxorubicin all have been used to treat advanced SCC with variable outcomes.

View full drug information

Docetaxel (Taxotere)

 

Docetaxel is a semisynthetic taxane, a class of drugs that inhibits cancer cell growth by promoting assembly and blocking the disassembly of microtubules, thereby preventing cancer cell division, leading to cell death. It is indicated in combination with cisplatin and 5-fluorouracil for induction therapy of locally advanced SCCHN before patients undergo chemoradiotherapy and surgery.

View full drug information

Methotrexate

 

Methotrexate is an antimetabolite that inhibits dihydrofolate reductase, thereby hindering DNA synthesis and cell reproduction in malignant cells. It has been used in combination with other chemotherapeutic agents for the treatment of cancers of the head and neck.

View full drug information

Paclitaxel

 

Paclitaxel is an antimicrotubule agent. Its mechanism of action includes tubulin polymerization and microtubule stabilization, which, in turn, inhibits mitosis and may result in breakage of chromosomes.

View full drug information

Carboplatin

 

Carboplatin is an analog of cisplatin. This is a heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation, leading to interstrand and intrastrand DNA cross-links and inhibition of DNA replication. It binds to protein and other compounds containing the SH group. It has been used in the treatment of advanced and recurrent SCCHN.

View full drug information

Bleomycin

 

Bleomycin is a cytotoxic glycopeptide antibiotic whose main mechanism of action may include inhibition of DNA synthesis and possible inhibition of RNA and protein synthesis. It is used as palliative treatment of SCCHN.

Previous
 
Contributor Information and Disclosures
Author

Marcus Monroe, MD  Resident Physician, Department of Otolaryngology, Head and Neck Surgery, Oregon Health and Science University

Marcus Monroe, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Coauthor(s)

Murad Alam, MD  Associate Professor of Dermatology, Otolaryngology, and Surgery; Chief, Section of Cutaneous and Aesthetic Surgery, Department of Dermatology, Northwestern University; Director, Mohs Micrographic Surgery, Northwestern Memorial Hospital

Murad Alam, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, American Dermatological Association, American Medical Association, American Society for Dermatologic Surgery, American Society for Laser Medicine and Surgery, American Society of Cosmetic Dermatology and Aesthetic Surgery, American Society of Transplantation, Dermatology Foundation, Illinois Dermatological Society, Phi Beta Kappa, Society for Investigative Dermatology, and Women's Dermatologic Society

Disclosure: Nothing to disclose.

William Joseph Campbell, MD  Resident Physician, Department of Surgery, University of Florida

William Joseph Campbell, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, and American Medical Student Association/Foundation

Disclosure: Nothing to disclose.

Jorge I de la Torre, MD, FACS  Professor of Surgery and Physical Medicine and Rehabilitation, Chief, Division of Plastic Surgery, Residency Program Director, University of Alabama at Birmingham School of Medicine; Director, Center for Advanced Surgical Aesthetics

Jorge I de la Torre, MD, FACS is a member of the following medical societies: American Association of Plastic Surgeons, American Burn Association, American College of Surgeons, American Medical Association, American Society for Laser Medicine and Surgery, American Society for Reconstructive Microsurgery, American Society of Maxillofacial Surgeons, American Society of Plastic Surgeons, Association for Academic Surgery, and Medical Association of the State of Alabama

Disclosure: Nothing to disclose.

Gregory Caputy, MD, PhD, FICS  Chief Surgeon, Aesthetica Plastic and Laser Surgery Center, Inc

Gregory Caputy, MD, PhD, FICS is a member of the following medical societies: American Society for Laser Medicine and Surgery, Canadian Medical Association, International College of Surgeons, International College of Surgeons US Section, Pan-Pacific Surgical Association, and Wound Healing Society

Disclosure: Syneron Corporation Salary Speaking and teaching

Christopher DeBacker, MD  Clinical Assistant Professor of Ophthalmology, University of Texas Health Science Center at San Antonio; Clinical Assistant Professor of Ophthalmology, University of California, San Francisco Medical Center, Veterans Affairs Medical Center

Christopher DeBacker, MD is a member of the following medical societies: American Academy of Cosmetic Surgery, American Academy of Ophthalmology, and American Society of Ophthalmic Plastic and Reconstructive Surgery

Disclosure: Nothing to disclose.

Robert M Dryden, MD, FACS  Clinical Professor, Department of Ophthalmology, University of Arizona School of Medicine

Robert M Dryden, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, American Academy of Cosmetic Surgery, American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Ophthalmology, American College of Surgeons, American Society of Ophthalmic Plastic and Reconstructive Surgery, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Mark T Duffy, MD, PhD  Consulting Staff, Division of Oculoplastic, Orbito-facial, Lacrimal and Reconstructive Surgery, Green Bay Eye Clinic, BayCare Clinic; Medical Director, Advanced Cosmetic Solutions, A BayCare Clinic

Mark T Duffy, MD, PhD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, American Society of Ophthalmic Plastic and Reconstructive Surgery, Sigma Xi, and Society for Neuroscience

Disclosure: Allergan - Botox Cosmetic Consulting fee Consulting

Jerre Freeman, MD  Founder and Chairman, Memphis Eye and Cataract Associates; Clinical Professor, Department of Ophthalmology, University of Tennessee Health Science Center College of Medicine

Jerre Freeman, MD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association, American Society of Cataract and Refractive Surgery, and Tennessee Medical Association

Disclosure: Nothing to disclose.

Jaime R Garza, MD, DDS, FACS  Consulting Staff, Private Practice

Jaime R Garza, MD, DDS, FACS is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American College of Surgeons, American Society for Aesthetic Plastic Surgery, American Society of Maxillofacial Surgeons, Texas Medical Association, and Texas Society of Plastic Surgeons

Disclosure: Nothing to disclose.

Neil D Gross, MD  Assistant Professor of Head and Neck Surgery and Oncology, Department of Otolaryngology – Head and Neck Surgery, Oregon Health and Science University

Neil D Gross, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Otolaryngology-Head and Neck Surgery, American Association for Cancer Research, American College of Surgeons, and American Head and Neck Society

Disclosure: Nothing to disclose.

Shahin Javaheri, MD  Chief, Department of Plastic Surgery, Martinez Veterans Affairs Outpatient Clinic; Consulting Staff, Advanced Aesthetic Plastic & Reconstructive Surgery

Shahin Javaheri, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery and American Society of Plastic Surgeons

Disclosure: Nothing to disclose.

Lorraine Jennings, MBBCh, MRCPI  Fellow, Department of Dermatology, Mohs Micrographic Surgery Center, Brigham and Women's Hospital, Harvard Medical School

Lorraine Jennings, MBBCh, MRCPI is a member of the following medical societies: British Association of Dermatologists, International Transplant and Skin Cancer Collaborative (ITSCC), Irish Association of Dermatologists, Photomedicine Society, and Royal College of Physicians of Ireland

Disclosure: Nothing to disclose.

Lawrence Ketch, MD, FAAP, FACS  Head, Program Director, Associate Professor, Department of Surgery, Division of Plastic Surgery, University of Colorado Health Sciences Center; Chief, Pediatric Plastic, The Children's Hospital of Denver

Lawrence Ketch, MD, FAAP, FACS is a member of the following medical societies: American Academy of Pediatrics, American Association for Hand Surgery, American Association of Plastic Surgeons, American Burn Association, American Cleft Palate/Craniofacial Association, American College of Surgeons, American Society for Surgery of the Hand, American Society of Maxillofacial Surgeons, American Society of Plastic Surgeons, Association for Academic Surgery, and Plastic Surgery Research Council

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD  Associate Professor of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, American Glaucoma Society, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Deepak Narayan, MD, FRCS  Associate Professor of Surgery (Plastic), Yale University School of Medicine; Chief of Plastic Surgery, West Haven Veterans Affairs Medical Center

Deepak Narayan, MD, FRCS is a member of the following medical societies: American Association for the Advancement of Science, American College of Surgeons, American Medical Association, American Society of Maxillofacial Surgeons, American Society of Plastic Surgeons, Indian Medical Association, Plastic Surgery Research Council, Royal College of Surgeons of Edinburgh, and Royal College of Surgeons of England

Disclosure: Nothing to disclose.

Ron W Pelton, MD, PhD  Private Practice, Colorado Springs, Colorado

Ron W Pelton, MD, PhD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, American Society of Ophthalmic Plastic and Reconstructive Surgery, AO Foundation, and Colorado Medical Society

Disclosure: Nothing to disclose.

Christopher J Rapuano, MD  Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Institute

Christopher J Rapuano, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Cataract and Refractive Surgery, Contact Lens Association of Ophthalmologists, Cornea Society, Eye Bank Association of America, International Society of Refractive Surgery, and Pan-American Association of Ophthalmology

Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; Inspire Honoraria Speaking and teaching; RPS Ownership interest Other; Vistakon Honoraria Speaking and teaching; EyeGate Pharma Consulting; Inspire Consulting fee Consulting; Bausch & Lomb Honoraria Speaking and teaching; Bausch & Lomb Consulting fee Consulting

Hampton Roy Sr, MD  Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, and Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Noah S Scheinfeld, MD, JD, FAAD  Assistant Clinical Professor, Department of Dermatology, Columbia University College of Physicians and Surgeons; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, and New York Eye and Ear Infirmary; Private Practice

Noah S Scheinfeld, MD, JD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Optigenex Consulting fee Independent contractor

Chrysalyne D Schmults, MD, MSCE  Assistant Professor of Dermatology, Harvard Medical School; Director, Mohs Micrographic Surgery Center, Department of Dermatology, Brigham and Women's Hospital and Dana Farber Cancer Center

Chrysalyne D Schmults, MD, MSCE is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, American Society for Dermatologic Surgery, and International Society for Dermatologic Surgery

Disclosure: Nothing to disclose.

Marvin Spann, MD  Staff Physician, Department of General Surgery, New York Hospital Queens

Disclosure: Nothing to disclose.

Wayne Karl Stadelmann, MD  Stadelmann Plastic Surgery, PC

Wayne Karl Stadelmann, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Surgeons, American Society of Plastic Surgeons, New Hampshire Medical Society, Northeastern Society of Plastic Surgeons, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Mia Talmor, MD  Assistant Professor, Department of Surgery, Weill Medical College of Cornell University

Mia Talmor, MD is a member of the following medical societies: American College of Surgeons and American Society of Plastic Surgeons

Disclosure: Nothing to disclose.

R Stan Taylor, MD  The JB Howell Professor in Melanoma Education and Detection, Departments of Dermatology and Plastic Surgery, Director, Skin Surgery and Oncology Clinic, University of Texas Southwestern Medical Center

R Stan Taylor, MD is a member of the following medical societies: American Academy of Dermatology, American College of Mohs Surgery, American Dermatological Association, American Medical Association, American Society for Dermatologic Surgery, Christian Medical & Dental Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Michael T Yen, MD  Associate Professor of Ophthalmology, Department of Ophthalmology, Division of Ophthalmic Plastic, Lacrimal, and Orbital Surgery, Cullen Eye Institute, Baylor College of Medicine

Michael T Yen, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Ophthalmic Plastic and Reconstructive Surgery, and Association for Research in Vision and Ophthalmology

Disclosure: Nothing to disclose.

Marc S Zimbler, MD, FACS  Director of Facial Plastic and Reconstructive Surgery, Director of Residency Education, Department of Otolaryngology, Head and Neck Surgery, Beth Israel Medical Center

Marc S Zimbler, MD, FACS is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery and American College of Surgeons

Disclosure: Nothing to disclose.

Specialty Editor Board

Samia Nawaz, MBBS, MD  Associate Professor, Department of Pathology, University of Colorado Health Science Center

Samia Nawaz, MBBS, MD is a member of the following medical societies: American Society for Clinical Pathology, American Society of Cytopathology, and International Academy of Pathology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

M Sherif Said, MD, PhD, FCAP  Associate Professor of Pathology, Director of Head and Neck Pathology, Department of Pathology, University of Colorado, Denver

M Sherif Said, MD, PhD, FCAP is a member of the following medical societies: American Society for Clinical Pathology and College of American Pathologists

Disclosure: Nothing to disclose.

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA  Professor, Department of Otolaryngology-Head and Neck Surgery, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, and American Head and Neck Society

Disclosure: Covidien Corp Consulting fee Consulting; US Tobacco Corporation Unrestricted gift Unknown; Axis Three Corporation Ownership interest Consulting; Omni Biosciences Ownership interest Consulting; Sentegra Ownership interest Board membership; Syndicom Ownership interest Consulting; Oxlo Consulting; Medvoy Ownership interest Management position; Cerescan Imaging Honoraria Consulting; GYRUS ACMI Honoraria Consulting

Acknowledgments

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Stephen D Hess, MD, PhD, Glenn Goldman, MD, Debjani Sahni, MBBS, MRCP, Laurence M Baibak, MD, FACS, and Charles W Vaughan, MD, FACS, to the development and writing of the source articles.

References

  1. Johnson TM, Rowe DE, Nelson BR, Swanson NA. Squamous cell carcinoma of the skin (excluding lip and oral mucosa). J Am Acad Dermatol. Mar 1992;26(3 Pt 2):467-84. [Medline].

  2. Salehi Z, Mashayekhi F, Shahosseini F. Significance of eIF4E expression in skin squamous cell carcinoma. Cell Biol Int. Nov 2007;31(11):1400-4. [Medline].

  3. Rowe DE, Carroll RJ, Day CL Jr. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. J Am Acad Dermatol. Jun 1992;26(6):976-90. [Medline].

  4. Brantsch KD, Meisner C, Schönfisch B, Trilling B, Wehner-Caroli J, Röcken M, et al. Analysis of risk factors determining prognosis of cutaneous squamous-cell carcinoma: a prospective study. Lancet Oncol. Aug 2008;9(8):713-20. [Medline].

  5. Newman MD, Weinberg JM. Topical therapy in the treatment of actinic keratosis and basal cell carcinoma. Cutis. Apr 2007;79(4 Suppl):18-28. [Medline].

  6. Katiyar SK. UV-induced immune suppression and photocarcinogenesis: chemoprevention by dietary botanical agents. Cancer Lett. Sep 18 2007;255(1):1-11. [Medline]. [Full Text].

  7. Ziegler A, Jonason AS, Leffell DJ, Simon JA, Sharma HW, Kimmelman J, et al. Sunburn and p53 in the onset of skin cancer. Nature. Dec 22-29 1994;372(6508):773-6. [Medline].

  8. Brash DE. Roles of the transcription factor p53 in keratinocyte carcinomas. Br J Dermatol. May 2006;154 Suppl 1:8-10. [Medline].

  9. Brown VL, Harwood CA, Crook T, Cronin JG, Kelsell DP, Proby CM. p16INK4a and p14ARF tumor suppressor genes are commonly inactivated in cutaneous squamous cell carcinoma. J Invest Dermatol. May 2004;122(5):1284-92. [Medline].

  10. Maclean H, Dhillon B, Ironside J. Squamous cell carcinoma of the eyelid and the acquired immunodeficiency syndrome. Am J Ophthalmol. Feb 1996;121(2):219-21. [Medline].

  11. Maurer TA, Christian KV, Kerschmann RL, Berzin B, Palefsky JM, Payne D, et al. Cutaneous squamous cell carcinoma in human immunodeficiency virus-infected patients. A study of epidemiologic risk factors, human papillomavirus, and p53 expression. Arch Dermatol. May 1997;133(5):577-83. [Medline].

  12. Verma V, Shen D, Sieving PC, Chan CC. The role of infectious agents in the etiology of ocular adnexal neoplasia. Surv Ophthalmol. Jul-Aug 2008;53(4):312-31. [Medline]. [Full Text].

  13. Gilberg SM, Tse DT. Malignant eyelid tumors. Ophthalmol Clin. 5:261-85.

  14. de Gruijl FR, Rebel H. Early events in UV carcinogenesis--DNA damage, target cells and mutant p53 foci. Photochem Photobiol. Mar-Apr 2008;84(2):382-7. [Medline].

  15. Perry PK, Silverberg NB. Cutaneous malignancy in albinism. Cutis. May 2001;67(5):427-30. [Medline].

  16. Zghal M, El-Fekih N, Fazaa B, Fredj M, Zhioua R, Mokhtar I, et al. [Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 49 Tunisian cases]. Tunis Med. Dec 2005;83(12):760-3. [Medline].

  17. Berg D, Otley CC. Skin cancer in organ transplant recipients: Epidemiology, pathogenesis, and management. J Am Acad Dermatol. Jul 2002;47(1):1-17; quiz 18-20. [Medline].

  18. Jensen P, Hansen S, Møller B, Leivestad T, Pfeffer P, Geiran O, et al. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol. Feb 1999;40(2 Pt 1):177-86. [Medline].

  19. Euvrard S, Kanitakis J, Decullier E, Butnaru AC, Lefrançois N, Boissonnat P, et al. Subsequent skin cancers in kidney and heart transplant recipients after the first squamous cell carcinoma. Transplantation. Apr 27 2006;81(8):1093-100. [Medline].

  20. Veness MJ, Quinn DI, Ong CS, Keogh AM, Macdonald PS, Cooper SG, et al. Aggressive cutaneous malignancies following cardiothoracic transplantation: the Australian experience. Cancer. Apr 15 1999;85(8):1758-64. [Medline].

  21. Black AP, Bailey A, Jones L, Turner RJ, Hollowood K, Ogg GS. p53-specific CD8+ T-cell responses in individuals with cutaneous squamous cell carcinoma. Br J Dermatol. Nov 2005;153(5):987-91. [Medline].

  22. Farshadpour F, Kranenborg H, Calkoen EV, et al. Survival analysis of head and neck squamous cell carcinoma: Influence of smoking and drinking. Head Neck. Jun 2011;33(6):817-23. [Medline].

  23. Wong SS, Tan KC, Goh CL. Cutaneous manifestations of chronic arsenicism: review of seventeen cases. J Am Acad Dermatol. Feb 1998;38(2 Pt 1):179-85. [Medline].

  24. Mallipeddi R. Epidermolysis bullosa and cancer. Clin Exp Dermatol. Nov 2002;27(8):616-23. [Medline].

  25. Fine JD, Johnson LB, Weiner M, Li KP, Suchindran C. Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986-2006. J Am Acad Dermatol. Feb 2009;60(2):203-11. [Medline].

  26. Reed WB, College J Jr, Francis MJ, Zachariae H, Mohs F, Sher MA, et al. Epidermolysis bullosa dystrophica with epidermal neoplasms. Arch Dermatol. Dec 1974;110(6):894-902. [Medline].

  27. Mallipeddi R, Keane FM, McGrath JA, Mayou BJ, Eady RA. Increased risk of squamous cell carcinoma in junctional epidermolysis bullosa. J Eur Acad Dermatol Venereol. Sep 2004;18(5):521-6. [Medline].

  28. Arbiser JL, Fan CY, Su X, Van Emburgh BO, Cerimele F, Miller MS, et al. Involvement of p53 and p16 tumor suppressor genes in recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma. J Invest Dermatol. Oct 2004;123(4):788-90. [Medline].

  29. Chang F, Syrjänen S, Kellokoski J, Syrjänen K. Human papillomavirus (HPV) infections and their associations with oral disease. J Oral Pathol Med. Aug 1991;20(7):305-17. [Medline].

  30. Marur S, Forastiere AA. Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc. Apr 2008;83(4):489-501. [Medline].

  31. Bouvard V, Baan R, Straif K, Grosse Y, Secretan B, El Ghissassi F, et al. A review of human carcinogens--Part B: biological agents. Lancet Oncol. Apr 2009;10(4):321-2. [Medline].

  32. Stockfleth E, Nindl I, Sterry W, Ulrich C, Schmook T, Meyer T. Human papillomaviruses in transplant-associated skin cancers. Dermatol Surg. Apr 2004;30(4 Pt 2):604-9. [Medline].

  33. Alam M, Caldwell JB, Eliezri YD. Human papillomavirus-associated digital squamous cell carcinoma: literature review and report of 21 new cases. J Am Acad Dermatol. Mar 2003;48(3):385-93. [Medline].

  34. Della Torre G, Donghi R, Longoni A, Pilotti S, Pasquini G, De Palo G, et al. HPV DNA in intraepithelial neoplasia and carcinoma of the vulva and penis. Diagn Mol Pathol. Mar 1992;1(1):25-30. [Medline].

  35. Lobo DV, Chu P, Grekin RC, Berger TG. Nonmelanoma skin cancers and infection with the human immunodeficiency virus. Arch Dermatol. May 1992;128(5):623-7. [Medline].

  36. Nguyen P, Vin-Christian K, Ming ME, Berger T. Aggressive squamous cell carcinomas in persons infected with the human immunodeficiency virus. Arch Dermatol. Jun 2002;138(6):758-63. [Medline].

  37. Karagas MR, Nelson HH, Zens MS, Linet M, Stukel TA, Spencer S, et al. Squamous cell and basal cell carcinoma of the skin in relation to radiation therapy and potential modification of risk by sun exposure. Epidemiology. Nov 2007;18(6):776-84. [Medline].

  38. Faustina M, Diba R, Ahmadi MA, Esmaeli B. Patterns of regional and distant metastasis in patients with eyelid and periocular squamous cell carcinoma. Ophthalmology. Oct 2004;111(10):1930-2. [Medline].

  39. Howard GR, Nerad JA, Carter KD, Whitaker DC. Clinical characteristics associated with orbital invasion of cutaneous basal cell and squamous cell tumors of the eyelid. Am J Ophthalmol. Feb 15 1992;113(2):123-33. [Medline].

  40. Leiter U, Garbe C. Epidemiology of melanoma and nonmelanoma skin cancer--the role of sunlight. Adv Exp Med Biol. 2008;624:89-103. [Medline].

  41. Masini C, Fuchs PG, Gabrielli F, Stark S, Sera F, Ploner M, et al. Evidence for the association of human papillomavirus infection and cutaneous squamous cell carcinoma in immunocompetent individuals. Arch Dermatol. Jul 2003;139(7):890-4. [Medline].

  42. Herman S, Rogers HD, Ratner D. Immunosuppression and squamous cell carcinoma: a focus on solid organ transplant recipients. Skinmed. Sep-Oct 2007;6(5):234-8. [Medline].

  43. Mehrany K, Weenig RH, Pittelkow MR, Roenigk RK, Otley CC. High recurrence rates of squamous cell carcinoma after Mohs' surgery in patients with chronic lymphocytic leukemia. Dermatol Surg. Jan 2005;31(1):38-42; discussion 42. [Medline].

  44. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Human papillomaviruses. IARC Monogr Eval Carcinog Risks Hum. 2007;90:1-636. [Medline].

  45. Harper JG, Pilcher MF, Szlam S, Lind DS. Squamous cell carcinoma in an African American with discoid lupus erythematosus: a case report and review of the literature. South Med J. Mar 2010;103(3):256-9. [Medline].

  46. American Cancer Society. Cancer facts and figures: 2004. Accessed February 2, 2011. Available at http://ww2.cancer.org/downloads/STT/CAFF_finalPWSecured.pdf.

  47. Hampton T. Skin cancer's ranks rise: immunosuppression to blame. JAMA. Sep 28 2005;294(12):1476-80. [Medline].

  48. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. Mar-Apr 2008;58(2):71-96. [Medline].

  49. Gray DT, Suman VJ, Su WP, Clay RP, Harmsen WS, Roenigk RK. Trends in the population-based incidence of squamous cell carcinoma of the skin first diagnosed between 1984 and 1992. Arch Dermatol. Jun 1997;133(6):735-40. [Medline].

  50. Mehta M, Fay A. Squamous cell carcinoma of the eyelid and conjunctiva. Int Ophthalmol Clin. Winter 2009;49(1):111-21. [Medline].

  51. Reifler DM, Hornblass A. Squamous cell carcinoma of the eyelid. Surv Ophthalmol. May-Jun 1986;30(6):349-65. [Medline].

  52. KWITKO ML, BONIUK M, ZIMMERMAN LE. Eyelid tumors with reference to lesions confused with squamous cell carcinoma. I. Incidence and errors in diagnosis. Arch Ophthalmol. Jun 1963;69:693-7. [Medline].

  53. McCarty JH, Barry M, Crowley D, Bronson RT, Lacy-Hulbert A, Hynes RO. Genetic ablation of alphav integrins in epithelial cells of the eyelid skin and conjunctiva leads to squamous cell carcinoma. Am J Pathol. Jun 2008;172(6):1740-7. [Medline]. [Full Text].

  54. Doxanas MT, Iliff WJ, Iliff NT, Green WR. Squamous cell carcinoma of the eyelids. Ophthalmology. May 1987;94(5):538-41. [Medline].

  55. Buettner PG, Raasch BA. Incidence rates of skin cancer in Townsville, Australia. Int J Cancer. Nov 23 1998;78(5):587-93. [Medline].

  56. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. Mar-Apr 2005;55(2):74-108. [Medline].

  57. McCall CO, Chen SC. Squamous cell carcinoma of the legs in African Americans. J Am Acad Dermatol. Oct 2002;47(4):524-9. [Medline].

  58. Edge SB, Byrd DR, Compton CC, eds. Cutaneous squamous cell carcinoma and other cutaneous carcinomas. In: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2009:301-9.

  59. Palme CE, MacKay SG, Kalnins I, Morgan GJ, Veness MJ. The need for a better prognostic staging system in patients with metastatic cutaneous squamous cell carcinoma of the head and neck. Curr Opin Otolaryngol Head Neck Surg. Apr 2007;15(2):103-6. [Medline].

  60. Jambusaria-Pahlajani A, Hess S, Berg D, Schmults CD. Equipoise exists in the peri-operative management of cutaneous squamous cell carcinoma with perineural invasion: A survey study of American College of Mohs Surgery surgeons. Manuscript under review.

  61. Clayman GL, Lee JJ, Holsinger FC, Zhou X, Duvic M, El-Naggar AK, et al. Mortality risk from squamous cell skin cancer. J Clin Oncol. Feb 1 2005;23(4):759-65. [Medline].

  62. Veness MJ, Morgan GJ, Palme CE, Gebski V. Surgery and adjuvant radiotherapy in patients with cutaneous head and neck squamous cell carcinoma metastatic to lymph nodes: combined treatment should be considered best practice. Laryngoscope. May 2005;115(5):870-5. [Medline].

  63. Ross AS, Schmults CD. Sentinel lymph node biopsy in cutaneous squamous cell carcinoma: a systematic review of the English literature. Dermatol Surg. Nov 2006;32(11):1309-21. [Medline].

  64. Cook BE Jr, Bartley GB. Epidemiologic characteristics and clinical course of patients with malignant eyelid tumors in an incidence cohort in Olmsted County, Minnesota. Ophthalmology. Apr 1999;106(4):746-50. [Medline].

  65. Dailey JR, Kennedy RH, Flaharty PM, Eagle RC Jr, Flanagan JC. Squamous cell carcinoma of the eyelid. Ophthal Plast Reconstr Surg. Sep 1994;10(3):153-9. [Medline].

  66. Thosani MK, Schneck G, Jones EC. Periocular squamous cell carcinoma. Dermatol Surg. May 2008;34(5):585-99. [Medline].

  67. Bowyer JD, Sullivan TJ, Whitehead KJ, Kelly LE, Allison RW. The management of perineural spread of squamous cell carcinoma to the ocular adnexae. Ophthal Plast Reconstr Surg. Jul 2003;19(4):275-81. [Medline].

  68. Donaldson MJ, Sullivan TJ, Whitehead KJ, Williamson RM. Squamous cell carcinoma of the eyelids. Br J Ophthalmol. Oct 2002;86(10):1161-5. [Medline]. [Full Text].

  69. Fleming MD, Hunt JL, Purdue GF, Sandstad J. Marjolin's ulcer: a review and reevaluation of a difficult problem. J Burn Care Rehabil. Sep-Oct 1990;11(5):460-9. [Medline].

  70. Møller R, Reymann F, Hou-Jensen K. Metastases in dermatological patients with squamous cell carcinoma. Arch Dermatol. Jun 1979;115(6):703-5. [Medline].

  71. Novick M, Gard DA, Hardy SB, Spira M. Burn scar carcinoma: a review and analysis of 46 cases. J Trauma. Oct 1977;17(10):809-17. [Medline].

  72. Kowal-Vern A, Criswell BK. Burn scar neoplasms: a literature review and statistical analysis. Burns. Jun 2005;31(4):403-13. [Medline].

  73. Ross AS, Whalen FM, Elenitsas R, Xu X, Troxel AB, Schmults CD. Diameter of involved nerves predicts outcomes in cutaneous squamous cell carcinoma with perineural invasion: an investigator-blinded retrospective cohort study. Dermatol Surg. Dec 2009;35(12):1859-66. [Medline].

  74. Frierson HF Jr, Deutsch BD, Levine PA. Clinicopathologic features of cutaneous squamous cell carcinomas of the head and neck in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. Hum Pathol. Dec 1988;19(12):1397-402. [Medline].

  75. Straif K, Benbrahim-Tallaa L, Baan R, Grosse Y, Secretan B, El Ghissassi F, et al. A review of human carcinogens--part C: metals, arsenic, dusts, and fibres. Lancet Oncol. May 2009;10(5):453-4. [Medline].

  76. Williams LS, Mancuso AA, Mendenhall WM. Perineural spread of cutaneous squamous and basal cell carcinoma: CT and MR detection and its impact on patient management and prognosis. Int J Radiat Oncol Biol Phys. Mar 15 2001;49(4):1061-9. [Medline].

  77. Robinson JW, Brownstein S, Jordan DR, Hodge WG. Conjunctival mucoepidermoid carcinoma in a patient with ocular cicatricial pemphigoid and a review of the literature. Surv Ophthalmol. Sep-Oct 2006;51(5):513-9. [Medline].

  78. Türegün M, Nisanci M, Güler M. Burn scar carcinoma with longer lag period arising in previously grafted area. Burns. Sep 1997;23(6):496-7. [Medline].

  79. Moy RL, Eliezri YD, Nuovo GJ, Zitelli JA, Bennett RG, Silverstein S. Human papillomavirus type 16 DNA in periungual squamous cell carcinomas. JAMA. May 12 1989;261(18):2669-73. [Medline].

  80. Barros JN, Lowen MS, Ballalai PL, Mascaro VL, Gomes JA, Martins MC. Predictive index to differentiate invasive squamous cell carcinoma from preinvasive ocular surface lesions by impression cytology. Br J Ophthalmol. Feb 2009;93(2):209-14. [Medline].

  81. Pe'er J. Ocular surface squamous neoplasia. Ophthalmol Clin North Am. Mar 2005;18(1):1-13, vii. [Medline].

  82. Papaioannou IT, Melachrinou MP, Drimtzias EG, Gartaganis SP. Corneal-conjunctival squamous cell carcinoma. Cornea. Sep 2008;27(8):957-8. [Medline].

  83. Gökmen Soysal H, Ardiç F. Malignant conjunctival tumors invading the orbit. Ophthalmologica. 2008;222(5):338-43. [Medline].

  84. Hirst LW, Axelsen RA, Schwab I. Pterygium and associated ocular surface squamous neoplasia. Arch Ophthalmol. Jan 2009;127(1):31-2. [Medline].

  85. Dorland's Illustrated Medical Dictionary. 28th ed. Philadelphia, Pa: WB Saunders; 1994.

  86. O'Brien CJ, McNeil EB, McMahon JD, Pathak I, Lauer CS, Jackson MA. Significance of clinical stage, extent of surgery, and pathologic findings in metastatic cutaneous squamous carcinoma of the parotid gland. Head Neck. May 2002;24(5):417-22. [Medline].

  87. Palme CE, O'Brien CJ, Veness MJ, McNeil EB, Bron LP, Morgan GJ. Extent of parotid disease influences outcome in patients with metastatic cutaneous squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. Jul 2003;129(7):750-3. [Medline].

  88. Andruchow JL, Veness MJ, Morgan GJ, Gao K, Clifford A, Shannon KF, et al. Implications for clinical staging of metastatic cutaneous squamous carcinoma of the head and neck based on a multicenter study of treatment outcomes. Cancer. Mar 1 2006;106(5):1078-83. [Medline].

  89. Audet N, Palme CE, Gullane PJ, Gilbert RW, Brown DH, Irish J, et al. Cutaneous metastatic squamous cell carcinoma to the parotid gland: analysis and outcome. Head Neck. Aug 2004;26(8):727-32. [Medline].

  90. Ch'ng S, Maitra A, Allison RS, Chaplin JM, Gregor RT, Lea R, et al. Parotid and cervical nodal status predict prognosis for patients with head and neck metastatic cutaneous squamous cell carcinoma. J Surg Oncol. Aug 1 2008;98(2):101-5. [Medline].

  91. Forest VI, Clark JJ, Veness MJ, Milross C. N1S3: a revised staging system for head and neck cutaneous squamous cell carcinoma with lymph node metastases: results of 2 Australian Cancer Centers. Cancer. Mar 1 2010;116(5):1298-304. [Medline].

  92. Lin LF, Chang CY, Cherng SC. Advanced squamous cell carcinoma of the bulbar conjunctiva seen on PET/CT. Clin Nucl Med. Dec 2008;33(12):929-30. [Medline].

  93. Dammann F, Horger M, Mueller-Berg M, Schlemmer H, Claussen CD, Hoffman J, et al. Rational diagnosis of squamous cell carcinoma of the head and neck region: comparative evaluation of CT, MRI, and 18FDG PET. AJR Am J Roentgenol. Apr 2005;184(4):1326-31. [Medline].

  94. Land R, Herod J, Moskovic E, King M, Sohaib SA, Trott P, et al. Routine computerized tomography scanning, groin ultrasound with or without fine needle aspiration cytology in the surgical management of primary squamous cell carcinoma of the vulva. Int J Gynecol Cancer. Jan-Feb 2006;16(1):312-7. [Medline].

  95. Cho SB, Chung WG, Yun M, Lee JD, Lee MG, Chung KY. Fluorodeoxyglucose positron emission tomography in cutaneous squamous cell carcinoma: retrospective analysis of 12 patients. Dermatol Surg. Apr 2005;31(4):442-6; discussion 446-7. [Medline].

  96. Gündüz K, Hosal BM, Zilelioglu G, Günalp I. The use of ultrasound biomicroscopy in the evaluation of anterior segment tumors and simulating conditions. Ophthalmologica. 2007;221(5):305-12. [Medline].

  97. Jambusaria-Pahlajani A, Miller CJ, Quon H, Smith N, Klein RQ, Schmults CD. Surgical monotherapy versus surgery plus adjuvant radiotherapy in high-risk cutaneous squamous cell carcinoma: a systematic review of outcomes. Dermatol Surg. Apr 2009;35(4):574-85. [Medline].

  98. Tan PY, Ek E, Su S, Giorlando F, Dieu T. Incomplete excision of squamous cell carcinoma of the skin: a prospective observational study. Plast Reconstr Surg. Sep 15 2007;120(4):910-6. [Medline].

  99. Holmkvist KA, Roenigk RK. Squamous cell carcinoma of the lip treated with Mohs micrographic surgery: outcome at 5 years. J Am Acad Dermatol. Jun 1998;38(6 Pt 1):960-6. [Medline].

  100. Rudkin AK, Muecke JS. Adjuvant 5-fluorouracil in the treatment of localised ocular surface squamous neoplasia. Br J Ophthalmol. Jul 2011;95(7):947-50. [Medline].

  101. Harwood CA, Leedham-Green M, Leigh IM, Proby CM. Low-dose retinoids in the prevention of cutaneous squamous cell carcinomas in organ transplant recipients: a 16-year retrospective study. Arch Dermatol. Apr 2005;141(4):456-64. [Medline].

  102. Char DH, Crawford JB. Orbital invasion despite topical anti-metabolite therapy for conjunctival carcinoma. Graefes Arch Clin Exp Ophthalmol. Mar 2008;246(3):459-61. [Medline].

  103. Shields CL, Demirci H, Marr BP, Masheyekhi A, Materin M, Shields JA. Chemoreduction with topical mitomycin C prior to resection of extensive squamous cell carcinoma of the conjunctiva. Arch Ophthalmol. Jan 2005;123(1):109-13. [Medline].

  104. Russell HC, Chadha V, Lockington D, Kemp EG. Topical mitomycin C chemotherapy in the management of ocular surface neoplasia: a 10-year review of treatment outcomes and complications. Br J Ophthalmol. Oct 2010;94(10):1316-21. [Medline].

  105. Bargman H, Hochman J. Topical treatment of Bowen's disease with 5-Fluorouracil. J Cutan Med Surg. Mar-Apr 2003;7(2):101-5. [Medline].

  106. Rosen T, Harting M, Gibson M. Treatment of Bowen's disease with topical 5% imiquimod cream: retrospective study. Dermatol Surg. Apr 2007;33(4):427-31; discussion 431-2. [Medline].

  107. Mackenzie-Wood A, Kossard S, de Launey J, Wilkinson B, Owens ML. Imiquimod 5% cream in the treatment of Bowen's disease. J Am Acad Dermatol. Mar 2001;44(3):462-70. [Medline].

  108. Smith KJ, Hamza S, Skelton H. Topical imidazoquinoline therapy of cutaneous squamous cell carcinoma polarizes lymphoid and monocyte/macrophage populations to a Th1 and M1 cytokine pattern. Clin Exp Dermatol. Sep 2004;29(5):505-12. [Medline].

  109. Perrett CM, McGregor JM, Warwick J, Karran P, Leigh IM, Proby CM, et al. Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy. Br J Dermatol. Feb 2007;156(2):320-8. [Medline]. [Full Text].

  110. Willey A, Mehta S, Lee PK. Reduction in the incidence of squamous cell carcinoma in solid organ transplant recipients treated with cyclic photodynamic therapy. Dermatol Surg. May 2010;36(5):652-8. [Medline].

  111. Marmur ES, Schmults CD, Goldberg DJ. A review of laser and photodynamic therapy for the treatment of nonmelanoma skin cancer. Dermatol Surg. Feb 2004;30(2 Pt 2):264-71. [Medline].

  112. Rossi R, Puccioni M, Mavilia L, Campolmi P, Mori M, Cappuccini A, et al. Squamous cell carcinoma of the eyelid treated with photodynamic therapy. J Chemother. Jun 2004;16(3):306-9. [Medline].

  113. [Best Evidence] Brewster AM, Lee JJ, Clayman GL, Clifford JL, Reyes MJ, Zhou X, et al. Randomized trial of adjuvant 13-cis-retinoic acid and interferon alfa for patients with aggressive skin squamous cell carcinoma. J Clin Oncol. May 20 2007;25(15):1974-8. [Medline].

  114. Braathen LR, Szeimies RM, Basset-Seguin N, Bissonnette R, Foley P, Pariser D, et al. Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005. J Am Acad Dermatol. Jan 2007;56(1):125-43. [Medline].

  115. Rio E, Bardet E, Ferron C, Peuvrel P, Supiot S, Campion L, et al. Interstitial brachytherapy of periorificial skin carcinomas of the face: a retrospective study of 97 cases. Int J Radiat Oncol Biol Phys. Nov 1 2005;63(3):753-7. [Medline].

  116. Veness M, Richards S. Role of modern radiotherapy in treating skin cancer. Australas J Dermatol. Aug 2003;44(3):159-66; quiz 167-8. [Medline].

  117. Wollina U, Hansel G, Koch A, Köstler E. Oral capecitabine plus subcutaneous interferon alpha in advanced squamous cell carcinoma of the skin. J Cancer Res Clin Oncol. May 2005;131(5):300-4. [Medline].

  118. Bauman JE, Eaton KD, Martins RG. Treatment of recurrent squamous cell carcinoma of the skin with cetuximab. Arch Dermatol. Jul 2007;143(7):889-92. [Medline].

  119. Suen JK, Bressler L, Shord SS, Warso M, Villano JL. Cutaneous squamous cell carcinoma responding serially to single-agent cetuximab. Anticancer Drugs. Aug 2007;18(7):827-9. [Medline].

  120. Arnold AW, Bruckner-Tuderman L, Zuger C, Itin PH. Cetuximab therapy of metastasizing cutaneous squamous cell carcinoma in a patient with severe recessive dystrophic epidermolysis bullosa. Dermatology. 2009;219(1):80-3. [Medline].

  121. Hitt R, Jimeno A, Rodríguez-Pinilla M, Rodríguez-Peralto JL, Millán JM, López-Martín A, et al. Phase II trial of cisplatin and capecitabine in patients with squamous cell carcinoma of the head and neck, and correlative study of angiogenic factors. Br J Cancer. Dec 13 2004;91(12):2005-11. [Medline]. [Full Text].

  122. Bentzen JD, Hansen HS. Phase II analysis of paclitaxel and capecitabine in the treatment of recurrent or disseminated squamous cell carcinoma of the head and neck region. Head Neck. Jan 2007;29(1):47-51. [Medline].

  123. Kim JG, Sohn SK, Kim DH, Baek JH, Jeon SB, Chae YS, et al. Phase II study of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck. Br J Cancer. Nov 14 2005;93(10):1117-21. [Medline]. [Full Text].

  124. Argiris A, Karamouzis MV, Raben D, Ferris RL. Head and neck cancer. Lancet. May 17 2008;371(9625):1695-709. [Medline].

  125. Otley CC, Cherikh WS, Salasche SJ, McBride MA, Christenson LJ, Kauffman HM. Skin cancer in organ transplant recipients: effect of pretransplant end-organ disease. J Am Acad Dermatol. Nov 2005;53(5):783-90. [Medline].

  126. Abou Ayache R, Thierry A, Bridoux F, Bauwens M, Belmouaz M, Desport E, et al. Long-term maintenance of calcineurin inhibitor monotherapy reduces the risk for squamous cell carcinomas after kidney transplantation compared with bi- or tritherapy. Transplant Proc. Oct 2007;39(8):2592-4. [Medline].

  127. Schena FP, Pascoe MD, Alberu J, del Carmen Rial M, Oberbauer R, Brennan DC, et al. Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial. Transplantation. Jan 27 2009;87(2):233-42. [Medline].

  128. Rival-Tringali AL, Euvrard S, Decullier E, Claudy A, Faure M, Kanitakis J. Conversion from calcineurin inhibitors to sirolimus reduces vascularization and thickness of post-transplant cutaneous squamous cell carcinomas. Anticancer Res. Jun 2009;29(6):1927-32. [Medline].

  129. Graham GF, Clark LC. Statistical analysis in cryosurgery of skin cancer. Clin Dermatol. Jan-Mar 1990;8(1):101-7. [Medline].

  130. Kuflik EG, Gage AA. The five-year cure rate achieved by cryosurgery for skin cancer. J Am Acad Dermatol. Jun 1991;24(6 Pt 1):1002-4. [Medline].

  131. Matsuo T, Ohara N, Namba Y, Koshima I, Ida K, Kanazawa S. Ophthalmic artery embolization as pretreatment of orbital exenteration for conjunctival squamous cell carcinoma. Cardiovasc Intervent Radiol. May 2009;32(3):554-7. [Medline].

  132. Brodland DG, Zitelli JA. Surgical margins for excision of primary cutaneous squamous cell carcinoma. J Am Acad Dermatol. Aug 1992;27(2 Pt 1):241-8. [Medline].

  133. Mohs FE. Micrographic surgery for the microscopically controlled excision of eyelid cancers. Arch Ophthalmol. Jun 1986;104(6):901-9. [Medline].

  134. Seidler AM, Bramlette TB, Washington CV, Szeto H, Chen SC. Mohs versus traditional surgical excision for facial and auricular nonmelanoma skin cancer: an analysis of cost-effectiveness. Dermatol Surg. Nov 2009;35(11):1776-87. [Medline].

  135. Rogers HW, Coldiron BM. A relative value unit-based cost comparison of treatment modalities for nonmelanoma skin cancer: effect of the loss of the Mohs multiple surgery reduction exemption. J Am Acad Dermatol. Jul 2009;61(1):96-103. [Medline].

  136. Robins P, Dzubow LM, Rigel DS. Squamous-cell carcinoma treated by Mohs' surgery: an experience with 414 cases in a period of 15 years. J Dermatol Surg Oncol. Oct 1981;7(10):800-1. [Medline].

  137. Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, et al. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science. Oct 18 1996;274(5286):373-6. [Medline].

  138. Roman S, Lindeman R, O'Toole G, Poole MD. Gene therapy in plastic and reconstructive surgery. Curr Gene Ther. Feb 2005;5(1):81-99. [Medline].

  139. Rea S, O'Sullivan ST. The polymerase chain reaction and its application to clinical plastic surgery. J Plast Reconstr Aesthet Surg. 2006;59(2):113-21. [Medline].

  140. Lee BJ, Wang SG, Choi JS, Lee JC, Goh EK, Kim MG. The prognostic value of telomerase expression in peripheral blood mononuclear cells of head and neck cancer patients. Am J Clin Oncol. Apr 2006;29(2):163-7. [Medline].

  141. Haddad R. Current and future directions in the treatment of squamous cell carcinoma of the head and neck: multidisciplinary symposium on head and neck cancer. Expert Opin Ther Targets. Apr 2006;10(2):333-6. [Medline].

  142. Seité S, Colige A, Piquemal-Vivenot P, Montastier C, Fourtanier A, Lapière C, et al. A full-UV spectrum absorbing daily use cream protects human skin against biological changes occurring in photoaging. Photodermatol Photoimmunol Photomed. Aug 2000;16(4):147-55. [Medline].

  143. Séite S, Moyal D, Richard S, de Rigal J, Lévêque JL, Hourseau C, et al. Mexoryl SX: a broad absorption UVA filter protects human skin from the effects of repeated suberythemal doses of UVA. J Photochem Photobiol B. Jun 15 1998;44(1):69-76. [Medline].

  144. Chen K, Craig JC, Shumack S. Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials. Br J Dermatol. Mar 2005;152(3):518-23. [Medline].

  145. Mrass P, Rendl M, Mildner M, Gruber F, Lengauer B, Ballaun C, et al. Retinoic acid increases the expression of p53 and proapoptotic caspases and sensitizes keratinocytes to apoptosis: a possible explanation for tumor preventive action of retinoids. Cancer Res. Sep 15 2004;64(18):6542-8. [Medline].

  146. Papoutsaki M, Lanza M, Marinari B, Nisticò S, Moretti F, Levrero M, et al. The p73 gene is an anti-tumoral target of the RARbeta/gamma-selective retinoid tazarotene. J Invest Dermatol. Dec 2004;123(6):1162-8. [Medline].

  147. Miller DL, Weinstock MA. Nonmelanoma skin cancer in the United States: incidence. J Am Acad Dermatol. May 1994;30(5 Pt 1):774-8. [Medline].

 
Previous
Next
 
Large, sun-induced squamous cell carcinoma on the forehead/temple with superficial erosion. Image courtesy of Glenn Goldman, MD.
Preauricular and helical scars (black arrows) from previous excisions are noted in a patient who presented with cervical metastases (white arrow) from an occult cutaneous squamous cell carcinoma (cSCC).
Contrast-enhanced, axial computed tomography (CT) scan of a patient with soft-tissue invasion of the right parotid gland (arrow) by an ulcerative cutaneous squamous cell carcinoma (cSCC).
Large, neglected cutaneous squamous cell carcinoma (cSCC) of the right ear that requires wide local excision via auriculectomy and reconstruction. The risk of lymph node metastasis with this deeply ulcerative tumor is sufficient enough to warrant elective neck dissection.
Squamous cell carcinoma in situ (Bowen disease). Courtesy of Hon Pak, MD.
cell carcinoma of the penis. Courtesy of Hon Pak, MD.
Extensive conjunctival squamous cell carcinoma of the left eye. The patient has limbal and corneal involvement temporally, as well as scleral invasion with intraocular spread. A malignant cellular reaction in the anterior chamber was present. The patient was treated with a lid-sparing exenteration.
A 35-year-old man who is positive with human immunodeficiency virus (HIV) infection presented with a 2-year history of a slowly enlarging, left lower eyelid lesion; incisional biopsy revealed squamous cell carcinoma.
Axial magnetic resonance image (MRI) of a large squamous cell carcinoma of the left lower eyelid with invasion of the anterior orbit.
External photograph of a large, ulcerated, invasive squamous cell carcinoma of the left lower eyelid. This patient also had perineural invasion of the infraorbital nerve extending into the cranial base.
Progressively severe atypia. The epithelium to the left is close to normal, but the epithelium to the right shows full-thickness atypia (ie, carcinoma in situ). This image illustrates carcinogenesis, the process whereby the cells exposed to a carcinogen become cancerous over time.
Squamous cell carcinoma. The lesion closely approximates the specimen in the previous image. Field cancerization is illustrated; that is, if >1 cell is exposed to a carcinogen, >1 cell becomes cancerous. Note the marked inflammatory-cell response. Should limited biopsy reveal only severe atypia with a severe inflammatory response, the lesion should be investigated further. A cancer is likely nearby.
Squamous cell carcinoma with spindle cell elements illustrates the totipotential nature of epithelial-cell malignancies.
Carcinoma in situ. Full-thickness atypia is clinically observed as a red-velvet patch (erythroplasia) and stains strongly with supravital stain, such as toluidine blue O.
Microinvasion and cellular atypia are observed deep to the expected junction between the epithelium and the stroma. Pink material (basement membrane) is evident around the clumps of malignant cells in the stroma. Surface keratin is present. On clinical evaluation, this lesion would have been observed as a white patch that does not rub off.
Invasion with normal surface. The top 4-5 cell layers are without atypia and mucosal surface changes. Toluidine blue O would not reveal the underlying cancer.
Specimen on a carrier. Vocal-fold epithelium has been stained with toluidine blue O, and all suspected tissue is excised (excisional biopsy). The specimen has been unfolded and laid flat onto a slice of cucumber. The specimen and cucumber are then flooded with fixative (10% formalin) and together serially sectioned for histologic evaluation.
This excisional biopsy specimen is well prepared for evaluation. The amorphous material deep to the specimen is the cucumber carrier. The specimen has been serially sectioned with alignment perpendicular to the surface to make evaluation of the entire specimen easy and reliable.
Fine-needle aspirate from a neck node. Clumps of cells obtained by means of fine-needle aspiration by using a 20-gauge needle and strong negative suction allow for histologic and cytologic evaluation. Sampling error is possible, particularly with small lesions.
This image depicts reddening of the soft palate, perhaps with scattered areas of white and velvet red patches; tobacco-induced squamous cell carcinoma involving the tongue base and/or supraglottis; and a firm, mobile mass that is palpable at the left carotid bifurcation.
This image shows scattered red and white patches, some of which are thick, with inflammation of the underlying mucosa.
Squamous cell carcinoma of the dorsal wrist. Courtesy of Hon Pak, MD.
Table 1. Estimated Number of New Cancer Cases and Deaths in Both Sexes in the United States in 2004
Cancer New Cases Deaths
Oral cavity and pharynx28,2607230
Tongue73201700
Mouth10,0801890
Pharynx82502070
Other oral cavity21601570
Larynx10,2703830
Source: American Cancer Society, 2004.[46]



Note: The US Census Bureau estimated that the US population was approximately 282,000,000.



Table 2. TNM Stage Grouping
Stage Primary Tumor Regional Lymph Nodes Distant Metastasis
Stage 0TisN0M0
Stage IT1N0M0
Stage IIT2N0M0
Stage IIIT3N0M0
T1, T2, T3N1M0
Stage IVT4N0, N1M0
Any TN2, N3M0
Any TAny NM1
Table 3. Histologic and Clinical Features of Squamous Cell Carcinoma (SCC) Variants
Tumor Histologic Characteristics Clinical Characteristics
KeratoacanthomaKeratin-filled crater



Well-differentiated (mild atypia)



Neutrophil microabscesses



Eosinophils in dermal infiltrate



Elastic tissue trapping



Lack of acantholysis



Solitary nodule



Central craterlike depression



Rapid growth



May spontaneously involute



Spindle cell carcinomaAtypical spindle cells



Foci of squamous differentiation



May resemble other spindle cell tumors (eg, atypical fibroxanthoma)



Resembles typical SCC



May be clinically aggressive



Acantholytic (adenoid) SCCGlandlike differentiation



Acantholysis



May resemble adenocarcinoma or sweat gland carcinoma



Arises on sun-damaged skin



Elderly patients



Resembles typical SCC



Clinically aggressive



Verrucous carcinomaWell-differentiated (glassy atypia)



Surface resembles verruca



Bulbous downward proliferation



"Bulldozing" invasion



Oral, genital, or plantar foot



Indolent growth



Locally destructive



Rarely metastasizes



Sarcomatoid SCCPoorly differentiated cells resembling sarcomaClinical appearance may be that of typical SCC or may have more nodular appearance with less surface change



Elevated risk of local recurrence and metastasis



Table 4. Summary of Characteristics of Papillary Epithelial Lesions and Verrucous Carcinoma
Tumor Epithelium Invasion and Inflammation
Benign squamous papillomaMinimal to no epithelial atypia without any stromal invasionNo inflammation in stroma; no epithelial cells, nests, or broad fronts in stroma
Papillary SCCISFull-thickness epithelial atypia without invasionNo invasive epithelial component in stroma; minimal inflammatory reaction
Papillary SCC, invasiveEpithelial atypia, which may or may not be full thickness, overlying stromal invasion; invasion occurs by means of elongated, stabbing fronts, small nests or individual cells Pointed, narrow epithelium extending into stroma, with epithelial nests and/or individual cells surrounded by inflammatory cells, which may be eosinophils, neutrophils, macrophages, plasma cells, and/or lymphocytes in any combination
Verrucous carcinomaBland, highly keratinized, squamous epithelium, with invasion in broad, rounded, pushing frontsNo individual cells or squamous nests in stroma; advanced portion of the epithelial pushing front surrounded by tightly hugging infiltrate of mononuclear inflammatory cells
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.