Therapeutic Options for Actinic Keratoses and Squamous Cell Carcinoma in Situ

Czech version

Authors: M. Pásek ¹
Authors‘ workplace: Dermatovenerologická klinika 3. LF UK a FNKV, Praha, přednosta prof. MUDr. Petr Arenberger, DrSc., MBA, FCMA ¹
Published in: Čes-slov Derm, 96, 2021, No. 5, p. 207-220
Category: Reviews (Continuing Medical Education)

Overview

Actinic keratoses (AK) are the most common precancerous lesions in the white Caucasian population due to long- -term exposure to ultraviolet (UV) radiation. Observations indicate its possible development into invasive cutaneous squamous cell carcinoma (cSCC). About 60–70% of invasive cSCC arises in pre-existing AK. Bowen's disease, bowenoid papulosis together with intraepithelial neoplasias (erythroplasia Queyrat), including penile vulvar and anal intraepithelial neoplasias, are classified as a group of squamous cell carcinomas in situ (Cis). Number of risk factors, especially UV radiation, chronic inflammation and infections with high-risk oncogenic HPV types 16 and 18, contribute to the etiology of Cis. Dermatoscopy, which is a highly sensitive, reliable, rapid and non-invasive diagnostic method, plays an important role in the diagnosis of AK. AK and Cis therapy can be divided into treatment focused on individual lesions (so-called lesion-directed therapy – e.g. cryotherapy, curettage, electrodesication, shave excision) or treatment focused on large areas (so-called field-directed therapy – e.g. 5 fluorouracil, imiquimod, ingenol mebutate, diclofenac sodium, photodynamic therapy).

Keywords:

Actinic keratosis – carcinoma in situ – dermatoscopy – Bowen’s disease – bowenoid papulosis – erythroplasia of Queyrat – penile intraepithelial neoplasia – vulvar intraepithelial neoplasia – high-grade squamous intraepithelial lesions – chemoprevention – lesion-directed therapy – field-directed therapy

Sources

1. ASGARI, M. M., ARRON, S. T., WEISSHAAR, D. et al. Sirolimus use and risk of cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients (SOTRs). J Am Acad Dermatol., 2015, 73(3), p. 444–450.

2. ASKEW, D. A., MICKAN, S. M., SOYER, H. P. et al. Effectiveness of 5-fluorouracil treatment for actinic keratosis and systematic review of randomized controlled trials. Int J Dermatol., 2009, 48(5), p. 453– 463.

3. BAVINCK, J. N., TIEBEN, L. M., VERMEER, B. J. et al. Prevention of skin cancer and reduction of keratotic skin lesions during acitretin therapy in renal recipients: a double blind, placebo-controlled study. J Clin Oncol., 1995, 13(8), p. 1933–1938.

4. BENÁKOVÁ, N. a kol. Moderní farmakoterapie v dermatologii. Praha: Maxdorf s.r.o., 2020. 647 s. ISBN 978-80-7345-653-5.

5. BOLOGNIA, J., SCHAFFER, J., CERRONI, L. et al. Dermatology: 2 Volume Set, 4th Edition. Elsevier. 2017, 2880 p., ISBN 9780702062759.

6. BRASH, D. E., RUDOLPH, J. A., SIMON, J. A. et al. A role for sunlight in skin cancer: UV-induced p53 mutations in squamous cell carcinoma. Proc Natl Acad Sci USA, 1991, 88(22), p. 10124–10128.

7. BUNKER, C. B., SHIM, T. N. Male Genital Lichen Sclerosus. Indian J Dermatol, 2015, 60(2), p. 111–117.

8. DODSON, J. M., DESPAIN, J., HEWETT, J. E. et al. Malignant potential of actinic keratoses and the controversy over treatment. A patient-oriented perspective. Arch Dermatol, 1991, 127(7), p. 1029– 1031.

9. ENDRIZZI, B., AHMED, R. L., LEE, P. et al. Capecitabine to reduce nonmelanoma skin carcinoma burden in solid organ transplant recipients. Dermatol Surg., 2013, 39(4), p. 634–645.

10. ENGEL, A., JOHNSON, M. L., HAYNES, S. G. et al. Health effects of sunlight exposure in the United States. Results from the first National Health and Nutrition Examination Survey, 1971–1974. Arch Dermatol, 1988, 124(1), p. 72–79.

11. ETTLER, K. Účinky UV záření na kůži a fotoprotekce. Med. Pro Praxi, 2007, 6, s. 273–275.

12. EUVRARD, S., MORELON, E., DANTAL, J. et al. TUMORAPA Study Group. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med., 2012, 367(4), p. 329–339.

13. FERNÁNDÉZ-FIGUERAS, M. T., CARRATO, C., SÁENZ, X. et al. Actinic keratosis with atypical basal cells (AK I) is the most common lesion associated with invasive squamous cell carcinoma of the skin. J Eur Acad Dermatol Venereol, 2015, 29(5), p. 991–997.

14. FERNÁNDÉZ-FIGUERAS, M. T. From actinic keratosis to squamous cell carcinoma pathophysiology revisited. J Eur Acad Dermatol Venereol, 2017, 31(Suppl. 2), p. 5–7.

15. FLOHIL, S. C., VAN DER LEEST, R. J., DOWLATSHAHI, E. A. et al. Prevalence of actinic keratosis and its risk factors in the general population: the Rotterdam Study. J Invest Dermatol, 2013, 133(8), p. 1971–1978.

16. GLOGAU, R. G. The risk of progression to invasive disease. J Am Acad Dermatol, 2000, 42(1 Pt 2), p. 23–24.

17. GREEN, A., WILLIAMS, G., NEALE, R., HART, V. et al. Daily sunscreen application and betacarotene supplementation in prevention of basal-cell and squamous- cell carcinomas of the skin: a randomised controlled trial. Lancet, 1999, 354 (9180), p. 723–729.

18. GUPTA, A. K., COOPER, E. A., FELDMAN, SROV. et al. A survey of office visits for actinic keratosis as reported by NAMCS, 1990–1999. National Ambulatory Medical Care Survey. Cutis, 2002, 70(2 Suppl), p. 8–13.

19. HADLEY, G., DERRY, S., MOORE, R. A. Imiquimod for actinic keratosis: systematic review and meta-analysis. J Invest Dermatol., 2006, 126(6), p. 1251–1255.

20. HERCOGOVÁ, J. a kol. Klinická Dermatoverelogie 1. díl, Praha: Mladá fronta a.s., 2019. 863 s. ISBN 978- 80-204-5321-1.

21. HOOGENDIJK-VAN DEN AKKER, J. M., HARDEN, P. N., de FIJTER, J. W. et al. Two-year randomized controlled prospective trial converting treatment of stable renal transplant recipients with cutaneous invasive squamous cell carcinomas to sirolimus. J Clin Oncol., 2013, 31(10), p. 1317–1323.

22. CHEN, G. J., FELDMAN, S. R., WILLIFORD, P. M. et al. Clinical diagnosis of actinic keratosis identifies an elderly population at high risk of developing skin cancer. Dermatol Surg, 2005, 31(1), p. 43–47.

23. CHEN, A. C., MARTIN, A. J., DAMIAN, D. L. et al. A phase 3 randomized trial of nicotinamide for skin-cancer prevention. N Engl J Med., 2015, 373(17), p. 1618–1626.

24. CHEN, A. C., MARTIN, A. J., DAMIAN, D. L. et al. A phase II randomized controlled trial of nicotinamide for skin cancer chemoprevention in renal transplant recipients. Br J Dermatol., 2016, 175(5), p. 1073–1075.

25. JANSEN, M. H. E., KESSELS, J., NELEMANS, P. J. et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med., 2019, 380, p. 935–946.

26. JIRAKULAPORN, T., ENDRIZZI, B., DUDEK, AZ. et al. Capecitabine for skin cancer prevention in solid organ transplant recipients. Clin Transpl., 2011, 25(4), p. 541–548.

27. KANG, S., GOLDFARB, M. T., GRIFFITHS, C. E. et al. Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial. J AmAcad Dermatol., 2003, 49(1), p. 83–90.

28. KARIA, P. S., AZZI, J. R., SCHMULTS, C. D. et al. Association of sirolimus use with risk for skin cancer in a mixed-organ cohort of solid-organ transplant recipients with a history of cancer. JAMA Dermatol., 2016, 152(5), p. 533–540.

29. KLEIN, A. M., BRASH, D. E., JONES, P. H. et al. Stochastic fate of p53-mutant epidermal progenitor cells is tilted toward proliferation by UVB during preneoplasia. Proc Natl Acad Sci USA, 2010, 107(1), p. 270–275.

30. KNIP, M., DOUEK, I. F., GALE, E. A. et al. European Nicotinamide Diabetes Intervention Trial Group. Safety of high-dose nicotinamide: a review. Diabetologia, 2000, 43, p. 1337–1345.

31. KOVACH, B. T., SAMS, H. H., STASKO, T. Systemic strategies for chemoprevention of skin cancers in transplant recipients. Clin Transpl., 2005, 19(6), p. 726–734.

32. KRAEMER, K. H., DIGIOVANNA, J. J., PECK, G. L. et al. Prevention of skin cancer in xeroderma pigmentosum with the use of oral isotretinoin. N Engl J Med., 1988, 318(25), p. 1633–1637.

33. KRAJSOVÁ, I. a kol. Maligní kožní nádory. Praha: Mladá fronta a.s., 2017. 287 s. ISBN 978-80-204- 4186-7.

34. KREJČÍ, D., SVOBODOVÁ, I., PEHALOVÁ, L. a kol. Novotvary 2017 ČR. Praha: ÚZIS. 2020. 350 s. ISSN: 1210- 857X.

35. LEBWOHL, M., SWANSON, N., BERMAN, B. et al. Ingenol mebutate gel for actinic keratosis. N Engl J Med., 2012, 366(11), p. 1010–1019.

36. LENS, M., MEDENICA, L. Systemic retinoids in chemoprevention of non-melanoma skin cancer. Expert Opin Pharmacother., 2008, 9(8), p. 1363– 1374.

37. MADANI, S., MARWAHA, S., DUSENDANG, J. R. et al. Ten-Year Follow-up of Persons With Sun-Damaged Skin Associated With Subsequent Development of Cutaneous Squamous Cell Carcinoma. JAMA Dermatol, 2021 [EPub Ahead of Print].

38. MAHMOUD, B. H., HEXSEL, C. L., HAMZAVI, I. H. et al. Effects of Visible Light on the Skin. Photochemistry and Photobiology, 2008, 84, p. 450–462.

39. MATHEW, T., KREIS, H., FRIEND, P. Two-year incidence of malignancy in sirolimus-treated renal transplant recipients: results from five multicenter studies. Clin Transpl., 2004, 18(4), p. 446– 449.

40. MCKENNA, D. B., MURPHY, G. M. Skin cancer chemoprophylaxis in renal transplant recipients: 5 years of experience using low-dose acitretin. Br J Dermatol., 2001, 140(4), p. 656–660.

41. MCKERROW, K. J., MACKIE, R. M., PEARSON, C. et al. The effect of oral retinoid therapy on the normal human immune system. Br J Dermatol., 1988, 119(3), p. 313–320.

42. MIKHAIL, G. R. Cancers, Precancers, and Pseudocancers on the Male Genitalia A Review of Clinical Appearances, Histopathology, and Management. The Journal of Dermatologic Surgery and Oncology, 1980, 6(12), p. 1027–1035.

43. MISIEWICZ, J., SENDAGORTA, E., GOLEBIOWSKA, A. Topical treatment of multiple actinic keratoses of the face with arotinoid methyl sulfone (Ro 14-9706) cream versus tretinoin cream: a double-blind, comparative study. J Am Acad Dermatol., 1991, 24(3), p. 448–451.

44. MORTON, C. A., BIRNIE, A. J., EEDY, D. J. et al. British Association of Dermatologists’ guidelines for the management of squamous cell carcinoma in situ (Bowen’s disease) 2014. Br J Dermatol, 2014, 170(2), p. 245–260.

45. MOSHELL, A. N. Prevention of skin cancer in xeroderma pigmentosum with oral isotretinoin. Cutis, 1989, 43(5), p. 485–490.

46. MURANUSHI, C., OLSEN, C. M., PANDEYA, N. et al. Aspirin and nonsteroidal anti-inflammatory drugs can prevent cutaneous squamous cell carcinoma: a systematic review and metaanalysis. J Invest Dermatol., 2015, 135(4), p. 975–983.

47. NANCE, F. C., DELOACH, D. H., WELSH, R. A., BECKER, W. F. Paget‘s disease of the breast. Ann Surg, 1970, 171(6), p. 864–874.

48. NGAN, V., OAKLEY, A., ROWAN, D. Vulvar intraepithelial neoplasia. Dostupné na www: https://www. dermnetnz.org/topica/vulval-intraepithelial-neoplasia.

49. OAKLEY, A. Lower anogenital squamous terminology. Dostupné na www: https://www.dermnetnz. org/topics/lower-anogenital-squamous-terminology.

50. OTLEY, C. C., STASKO, T., LEBWOHL, M. et al. Chemoprevention of nonmelanoma skin cancer with systemic retinoids: practical dosing and management of adverse effects. Dermatol Surg., 2006, 32(4), p. 562–568.

51. PATEL, G. K., GOODWIN, R., CHAWLA, M. et al. Imiquimod 5% cream monotherapy for cutaneous squamous cell carcinoma in situ (Bowen’s disease): a randomized, double blind, placebo-controlled trial. J AmAcadDermatol., 2006, 54(6), p. 1025–1032.

52. PINNELL, S. R. Cutaneous photodamage, oxidative stress, and topical antioxidant protection. J Am Acad Dermatol., 2003, 48(1), p. 1–19.

53. PIRARD, D., VEREECKEN, P., HEENEN, M. et al. Three percent diclofenac in 2.5% hyaluronan gel in the treatment of actinic keratoses: a meta-analysis of the recent studies. Arch Dermatol Res., 2005, 297(5), p. 185–189.

54. PRENS, S. P., de VRIES, K., PRENS, E. P. et al. Non-ablative fractional resurfacing in combination with topical tretinoin cream as a field treatment modality for multiple actinic keratosis: a pilot study and a review of other field treatment modalities. J Dermatolog Treat., 2013, 24(3), p. 227–231.

55. QUE, S. K. T., ZWALD, F. O., SCHMULTS, C. D. Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol, 2018, 78(2), p. 237–247.

56. QUE, S. K. T., ZWALD, F. O., SCHMULTS, C. D. Cutaneous squamous cell carcinoma, Management of advanced and high-stage tumors. J Am Acad Dermatol, 2018, 78(2), p. 249–261.

57. SALIM, A., LEMAN, J. A., MORTON, C. A. et al. Randomized comparison of photodynamic therapy with topical 5-fluorouracil in Bowen’s disease. Br J Dermatol., 2003, 148(3), p. 539–543.

58. SEANZ-SARDÁ, X., CARRATO, C., PERÉZ-ROCA, L. et al. Epithelial-to-mesenchymal transition contributes to invasion in squamous cell carcinomas originated from actinic keratosis through the differentiated pathway whereas proliferation plays a more significant role in the classical pathway. J Eur Acad Dermatol Venereol, 2017, 32(4), p. 581–586.

59. SCHMITZ, L., GAMBICHLER, T., GUPTA, G. et al. Actinic keratosis area and severity index (AKASI) is associated with the incidence of squamous cell carcinoma. J Eur Acad Dermatol Venereol., 2018, 32(5), p. 752–756.

60. SCHMULTS, C. D. et al. High-Risk Cutaneous Squamous Cell Carcinoma – A Practical Guide for Patient Management. Berlin: Springer International Publishing, 2016. 261 p. ISBN 978-3-662- 47080-0.

61. STOCKFLETH, E., SCHMITZ, L. Braun-Falco´s Dermatology, Malignant Epithelial Tumors. Berlin: Springer International Publishing, 2020. 24 p. ISBN 978- 3-662-58713-3.

62. SURJANA, D., HALLIDAY, G. M., DAMIAN, D. L. Nicotinamide enhances repair of ultraviolet radiation- induced DNA damage in human keratinocytes and ex vivo skin. Carcinogenesis, 2013, 34(5), p. 1144–1149.

63. VAN DER POLS, J. C., WILLIAMS, G. M., PANDEYA, N. et al. Prolonged prevention of squamous cell carcinoma of the skin by regular sunscreen use. Cancer Epidemiol Biomarkers Prev., 2006, 15(12), p. 2546–2548.

64. WEINSTOCK, M. A., BINGHAM, S. F., VERTREES, J. E. et al. Veterans Affairs Topical Tretinoin Chemoprevention Trial Group. Tretinoin and the prevention of keratinocyte carcinoma (basal and squamous cell carcinoma of the skin): a Veterans Affairs randomized chemoprevention trial. J Invest Dermatol., 2012, 132(6), p. 1583–1590.

65. WERNER, R. N., SAMMAIN, A., ERDMANN, R. et al. The natural history of actinic keratosis: a systematic review. Br J Dermatol, 2013, 169(3), p. 502–518.

66. WIEGELL, S. R., HAEDERSHAL M., WULF, H. C. et al. Continuous activation of PpIX by daylight is as effective as and less painful than conventional photodynamic therapy for actinic keratoses; a randomized, controlled, single-blinded study. Br J Dermatol., 2008, 158(4), p. 740–746.

67. WIEGELL, S. R., HAEDERSHAL M., WULF, H. C. et al. Photodynamic therapy of actinic keratoses with 8% and 16% methyl aminolaevulinate and home-based daylight exposure: a double-blinded randomized clinical trial. Br J Dermatol., 2009, 160(6), p. 1308–1314.

68. WIEGELL, S. R., FABRICIUS, S., WULF, H. C. et al. A randomized, multicentre study of directed daylight exposure times of 1½ vs 2½ h in daylight-mediated photodynamic therapy with methyl aminolaevulinate in patients with multiple thin actinic keratoses of the face and scalp. Br J Dermatol., 2011, 164(5), p. 1083–1090.

69. WILLENBRINK, T. J., RUIZ, E. S., CORNEJO, CHM. et al. Field cancerization: Definition, epidemiology, risk factors, and outcomes. J Am Acad Dermatol., 2020, 83(3), p. 709–717.

70. WOLLINA, U., HANSEL, G., KÖSTLER, E. et al. Oral capecitabine plus subcutaneous interferon alpha in advanced squamous cell carcinoma of the skin. J Cancer Res Clin Oncol., 2005, 131(5), p. 300–304.

71. YIASEMIDES, E., SIVAPIRABU, G., DAMIAN, D. L. et al. Oral nicotinamide protects against ultraviolet radiation induced immunosuppression in humans. Carcinogenesis, 2009, 30(1), p. 101–105.

72. YU, R. C., PRYCE, D. W., MACFARLANE, A. W. et al. A histopathological study of 643 cutaneous horns. Br J Dermatol, 1991, 124(5), p. 449–452.

73. ZALAUDEK, I., ARGENZIANO, G., GIACOMEL, J. et al. Dermatoscopy of Non-Pigmented Skin Tumors: Pink – Think – Blink (1st ed.). Boca Raton: CRS Press, 2015. 158 p. ISBN 978-1-4822-3753-5.

Labels

Dermatology & STDs Paediatric dermatology & STDs

KONTROLNÍ TEST

Reccurent Herpetic Paronychia (Herpetic Whitlow). Case report

Scrotal Calcinosis. Minireview

Combined Naevus with Pigmented Epithelioid Melanocytoma. Case Report

Odborné akce 2021

16. KONGRES ČESKÝCH A SLOVENSKÝCH DERMATOVENEROLOGŮ

Article was published in

Czech-Slovak Dermatology

2021 Issue 5