Tracing human papillomavirus in skin and mucosal squamous cell carcinoma: a histopathological retrospective survey


Submitted: 22 August 2023
Accepted: 12 November 2023
Published: 1 February 2024
Abstract Views: 325
PDF: 261
HTML: 32
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

  • Ali Nili Infectious Diseases and Tropical Medicine Research Center, AJA University of Medical Sciences, Tehran; Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Iran, Islamic Republic of.
  • Maryam Daneshpazhooh Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Iran, Islamic Republic of.
  • Hamidreza Mahmoudi Autoimmune Bullous Diseases Research Center, Tehran University of Medical Sciences, Iran, Islamic Republic of.
  • Kambiz Kamyab Department of Dermatopathology, Tehran University of Medical Sciences, Iran, Islamic Republic of.
  • Shirin Taraz Jamshidi Department of Dermatopathology, Tehran University of Medical Sciences; Department of Pathology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran, Islamic Republic of.
  • Saeed Soleiman-Meigooni Infectious Diseases and Tropical Medicine Research Center, AJA University of Medical Sciences, Tehran, Iran, Islamic Republic of.
  • Mohammad Darvishi Infectious Diseases and Tropical Medicine Research Center, AJA University of Medical Sciences, Tehran; Department of Aerospace and Subaquatic Medicine, AJA University of Medical Sciences, Tehran, Iran, Islamic Republic of.

Worldwide, squamous cell carcinoma (SCC) incidence is rising. The literature debates the human papillomavirus (HPV)’s role in cutaneous SCC development. We examined HPV histopathology in SCC samples in this study. Retrospective study at tertiary referral skin center in 2020. Histopathological features of HPV, including koilocytosis, hyperkeratosis, acanthosis, hypergranulosis, parakeratosis, solar elastosis, papillomatosis, and tumor grade, were examined in SCC specimens. Two dermatopathologists independently reevaluated all samples. We examined 331 SCC cases (male:female ratio = 3.9:1). The mean age was 68.1, with 15.1 standard deviation. Lesions were most common on the face (40.5%), scalp (22.7%), and extremities (20.8%). Koilocytes were found in 50 (15.1%) lesions. Nail (38.1%, p=0.007), oral cavity (36.8%, p=0.014), and genitalia (60.0%, p=0.026) lesions had higher koilocytosis rates. SCCs were found in 6.6% of specimens, but in situ tumors had the highest koilocytosis (64.7%), significantly higher than other grades (p<0.001). SCC pathology often shows HPV and specific koilocyte histopathology. Well-differentiated SCC has a stronger association with nail, oral, and genital lesions.


Tavakolpour S, Daneshpazhooh M, Mahmoudi H. Skin Cancer: Genetics, Immunology, Treatments, and Psychological Care. In: Mehdipour P. (ed.). Cancer Genetics and Psychotherapy. Cham: Springer International Publishing; 2017.

Prieto-Granada C, Rodriguez-Waitkus P. Cutaneous squamous cell carcinoma and related entities: Epidemiology, clinical and histological features, and basic science overview. Curr Probl Cancer 2015;39:206-15.

Gloster HM Jr., Neal K. Skin cancer in skin of color. J Am Acad Dermatol 2006;55:741-60; quiz 761-4.

Aldabagh B, Angeles JG, Cardones AR, Arron ST. Cutaneous squamous cell carcinoma and human papillomavirus: is there an association? Dermatol Surg 2013;39:1-23.

Jensen P, Hansen S, Møller B, et al. Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens. J Am Acad Dermatol 1999;40:177-86.

Lindelöf B, Sigurgeirsson B, Gäbel H, Stern RS. Incidence of skin cancer in 5356 patients following organ transplantation. Br J Dermatol 2000;143:513-9.

Arron ST, Jennings L, Nindl I, et al. Viral oncogenesis and its role in nonmelanoma skin cancer. Br J Dermatol 2011;164:1201-13.

Vajdic CM, Mcdonald SP, Mccredie MR, et al. Cancer incidence before and after kidney transplantation. JAMA 2006;296:2823-31.

Koss LG. The 57th birthday of koilocytes. Cancer Cytopathol 2012;120:421.

Gheit T. Mucosal and Cutaneous Human Papillomavirus Infections and Cancer Biology. Front Oncol 2019;9.

Duensing S, Münger K. Mechanisms of genomic instability in human cancer: Insights from studies with human papillomavirus oncoproteins. Int J Cancer 2004;109:157-62.

Krawczyk E, Suprynowicz FA, Liu X, et al. Koilocytosis: a cooperative interaction between the human papillomavirus E5 and E6 oncoproteins. Am J Pathol 2008;173:682-8.

Zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2002;2:342-50.

Cardoso JC, Calonje E. Cutaneous manifestations of human papillomaviruses: a review. Acta Dermatovenerol Alp Pannonica Adriat 2011;20:145-54.

Syrjänen S. The role of human papillomavirus infection in head and neck cancers. Ann Oncol 2010;21:vii243-5.

Harwood CA, Surentheran T, Sasieni P, et al. Increased risk of skin cancer associated with the presence of epidermodysplasia verruciformis human papillomavirus types in normal skin. Br J Dermatol 2004;150:949-57.

Cho NH, Kang S, Hong S, et al.. Multinucleation of koilocytes is in fact multilobation and is related to aberration of the G2 checkpoint. J Clin Pathol 2005;58:576-82.

Lawson JS, Glenn WK, Heng B, et al. Koilocytes indicate a role for human papilloma virus in breast cancer. Br J Cancer 2009;101:1351-6.

Okodo M, Okayama K, Teruya K, et al. Koilocytic changes are not elicited by human papillomavirus genotypes with higher oncogenic potential. J Med Virol 2020;92:3766-73.

Reid R, Stanhope CR, Herschman BR, et al. Genital warts and cervical cancer. I. Evidence of an association between subclinical papillomavirus infection and cervical malignancy. Cancer 1982;50:377-87.

Roteli-Martins CM, Derchain SF, Martinez EZ, et al. Morphological diagnosis of HPV lesions and cervical intraepithelial neoplasia (CIN) is highly reproducible. Clin Exp Obstet Gynecol 2001;28:78-80.

Boon ME, Kok LP. Koilocytotic lesions of the cervix: the interrelation of morphometric features, the presence of papilloma- virus antigens, and the degree of koilocytosis. Histopathology 1985;9:751-63.

Martins RH, Dias NH, Gregório EA, et al. Laryngeal papillomatosis: morphological study by light and electron microscopy of the HPV-6. Braz J Otorhinolaryngol 2008;74:539-43.

Miller BA, Davidson M, Myerson D, et al. Human papillomavirus type 16 DNA in esophageal carcinomas from Alaska Natives. Int J Cancer 1997;71:218-22.

Aggarwal S, Arora VK, Gupta S, et al. Koilocytosis: correlations with high-risk HPV and its comparison on tissue sections and cytology, urothelial carcinoma. Diagn Cytopathol 2009;37:174-7.

Sias C, Salichos L, Lapa D, et al. Alpha, Beta, gamma human papillomaviruses (HPV) detection with a different sets of primers in oropharyngeal swabs, anal and cervical samples. Virol J 2019;16:27.

De Villiers EM, Fauquet C, Broker TR, et al. Classification of papillomaviruses. Virology 2004;324:17-27.

Bouvard V, Baan R, Straif K, et al. A review of human carcinogens-- Part B: biological agents. Lancet Oncol 2009;10:321-2.

Halec G, Schmitt M, Dondog B, et al. Biological activity of probable/possible high-risk human papillomavirus types in cervical cancer. Int J Cancer 2013;132:63-71.

Mahmoudi H, Ghodsi SZ, Tavakolpour S, Daneshpazhooh M. Cryotherapy plus oral zinc sulfate versus cryotherapy plus placebo to treat common warts: A double blind, randomized, placebo-controlled trial. Int J Womens Dermatol 2018;4:87-90.

Plummer M, De Martel C, Vignat J, et al. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Glob Health 2016;4:e609-16.

Ashinoff R, Li JJ, Jacobson M, et al. Detection of Human Papillomavirus DNA in Squamous Cell Carcinoma of the Nail Bed and Finger Determined by Polymerase Chain Reaction. Arch Dermatol 1991;127:1813-8.

Dika E, Venturoli S, Patrizi A, et al. The detection of human papillomavirus-16 in squamous cell carcinoma of the nail unit: A case series. J Am Acad Dermatol 2017;76:354-6.

Iorga L, Dragos Marcu R, Cristina Diaconu C, et al. Penile carcinoma and HPV infection (Review). Exp Therap Med 2020;20:91-6.

Miyahara GI, Simonato LE, Mattar NJ, et al. Correlation between koilocytes and human papillomavirus detection by PCR in oral and oropharynx squamous cell carcinoma biopsies. Memórias do Instituto Oswaldo Cruz 2011;106:166-9.

Muñoz N, Bosch FX, De Sanjosé S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;348:518-27

Riddel C, Rashid R, Thomas V. Ungual and periungual human papillomavirus-associated squamous cell carcinoma: a review. J Am Acad Dermatol 2011;64:1147-53.

Sanderson RJ, Ironside JA. Squamous cell carcinomas of the head and neck. BMJ 2002;325:822-7.

Wang J, Aldabagh B, Yu J, Arron ST. Role of human papillomavirus in cutaneous squamous cell carcinoma: a meta-analysis. J Am Acad Dermatol 2014;70:621-9.

Forslund O, Iftner T, Andersson K, et al. Cutaneous human papillomaviruses found in sun-exposed skin: Beta-papillomavirus species 2 predominates in squamous cell carcinoma. J Infect Dis 2007;196:876-83.

Gillison ML, Koch WM, Capone RB, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst 2000;92:709-20.

Kreimer AR, Clifford GM, Boyle P, Franceschi S. Human papillomavirus types in head and neck squamous cell carcinomas worldwide: a systematic review. Cancer Epidemiol Biomarkers Prev 2005;14:467-75.

Weinberger PM, Yu Z, Haffty BG, et al. Molecular classification identifies a subset of human papillomavirus--associated oropharyngeal cancers with favorable prognosis. J Clin Oncol 2006;24:736-47.

Lassen P, Eriksen JG, Hamilton-Dutoit S, et al. Effect of HPVassociated p16INK4A expression on response to radiotherapy and survival in squamous cell carcinoma of the head and neck. J Clin Oncol 2009;27:1992-8.

Licitra L, Perrone F, Bossi P, et al. High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. J Clin Oncol 2006;24:5630-6.

Lindquist D, Romanitan M, Hammarstedt L, et al. Human papillomavirus is a favourable prognostic factor in tonsillar cancer and its oncogenic role is supported by the expression of E6 and E7. Mol Oncol 2007;1:350-5.

Kreimer AR, Johansson M, Waterboer T, et al. Evaluation of human papillomavirus antibodies and risk of subsequent head and neck cancer. J Clin Oncol 2013;31:2708-15.

Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010;363:24-35.

Dahlstrand H, Dahlgren L, Lindquist D, et al. Presence of human papillomavirus in tonsillar cancer is a favourable prognostic factor for clinical outcome. Anticancer Res 2004;24:1829-35.

Abadi MA, Ho GYF, Burk RD, et al. Stringent criteria for histological diagnosis of koilocytosis fail to eliminate overdiagnosis of human papillomavirus infection and cervical intraepithelial neoplasia grade 1. Human Pathol 1998;29:54-9.

Nili, A., Daneshpazhooh, M., Mahmoudi, H., Kamyab, K., Jamshidi, S. T., Soleiman-Meigooni, S., & Darvishi, M. (2024). Tracing human papillomavirus in skin and mucosal squamous cell carcinoma: a histopathological retrospective survey. Dermatology Reports, 16(2). https://doi.org/10.4081/dr.2024.9833

Downloads

Download data is not yet available.

Citations