Review
Ungual and periungual human papillomavirus–associated squamous cell carcinoma: A review

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Background

Human papillomavirus (HPV)–associated squamous cell carcinoma (SCC) and SCC in situ are often reported in the genital region. The association of HPV with SCC in the ungual and periungual skin is less well recognized, and verrucous lesions may undergo years of therapeutic attempts without a diagnostic biopsy.

Objectives

To review the epidemiology, associations, and role of HPV in digital SCC and SCC in situ.

Methods

The English-language literature reporting HPV-associated SCC and SCC in situ of the digits was reviewed.

Results

HPV-associated SCC and SCC in situ were almost equally represented. The patients' ages ranged from 22 to 89 years, with men affected twice as often as women. HPV16 was the most common subtype. The tumors presented as persistent verrucae, present for an average of 5.3 years. Immune suppression was documented in only 6.8% of patients. Approximately 6% of cases required digital amputation.

Limitations

Most of the information was obtained from case reports, some of which had limited data regarding the exact location of the tumor and the diagnostic and treatment course. HPV subtyping is not commonly performed in these tumors, which limited the number of reports that could be evaluated.

Conclusions

The majority of digital HPV-associated SCCs or SCCs in situ involves the nailbed region. The clinical appearance is most commonly that of a periungual verruca. Tumors have a higher rate of recurrence after excision than SCC in other sites. Periungual and subungual warts caused by high-risk HPV subtypes pose a risk for malignant transformation in both immunocompetent and immunocompromised hosts.

Introduction

The oncogenic role of human papillomavirus (HPV) in squamous cell carcinoma (SCC) has been well established. Outside the genital region, HPV-associated tumors are found primarily on the hands and feet, particularly in the area of the nail bed. We review reports of HPV-associated carcinoma of the digit, particularly in the area of the nailbed, as well as the epidemiological factors, clinical associations, and management of these tumors.

Section snippets

Methods

A literature search was performed on MEDLINE, PubMed, and Ovid. Manuscripts were reviewed to identify reports of HPV-associated SCC and SCC in situ in the ungual and periungual regions. Citations were reviewed to avoid potential oversight of older manuscripts. Initially, we limited our search to reports with at least 10 cases; however, because there were few case series in the literature, we expanded the search to include any report of HPV-associated SCC. Key words searched include HPV, ungual,

Results

Our review identified 103 patients reported in the English-language literature with HPV-associated digital SCC or SCC in situ (Bowen's disease) over a 26-year period (1983-2009). More than 50 reports of subungual and periungual SCC without HPV typing studies were excluded. There were 120 individual tumors on the fingers and toes. Fifteen cases did not specify the affected digit, and 23 reports did not indicate a specific location on the digit. Fourteen cases did not specify the hand on which

Discussion

The strongest evidence for the oncogenic role of HPV lies in SCC of the cervix, which is virtually always associated with high-risk mucosal HPV subtypes.44 Outside the genital area, HPV-associated cutaneous SCC and SCC in situ are seen in epidermodysplasia verruciformis and immunocompromised patients, such as in those undergoing kidney transplantation or those with HIV infection. In immunocompetent patients, the majority of cutaneous malignancies associated with HPV outside the genital area

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    Funding sources: None.

    Conflicts of interest: None declared.

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