TOPLINE:

A multicenter retrospective review of 269 nail unit squamous cell carcinoma (NSCC) cases found that human papillomavirus (HPV)-related lesions were more often periungual and in situ, whereas subungual tumors with oozing were more often invasive and painful.

METHODOLOGY:

• Researchers retrospectively reviewed 269 histopathologically confirmed NSCCs in 261 patients. The mean patient age was 60.7 years, 72.4% were male, 21.1% were current or former smokers, and 7.3% had a history of immunosuppression.
• Overall, 55% of tumors were classified as NSCC in situ and 45% as invasive NSCC. HPV status was assessed using koilocytosis and confirmed by polymerase chain reaction (PCR); 47 of 146 tumors (32.2%) showed koilocytosis, and 15 of 21 tested tumors were confirmed HPV-positive by PCR.
• The mean time to diagnosis was 3.1 years; most tumors involved thumbs (16.3% on the right, 13.9% on the left) and right index (16.7%) and middle (15.5%) fingers.
• Researchers compared patient and tumor characteristics between in situ and invasive NSCC and analyzed treatment and recurrences. The mean follow-up duration was 2.7 years.

TAKEAWAY:

• Compared with in situ NSCC, invasive NSCC was associated with older age (mean 64.6 vs 57.4 years, P < .001), present or past smoking (28.1% vs 15.5%, P = .017), and presentation with subungual ooze (53.7% vs 16.2%, P < .001), pain (43.8% vs 27.0%, P = .022), and loss of nail plate production (50.4% vs 32.4%, P = .004). Subungual ooze independently predicted invasive NSCC (adjusted odds ratio [OR], 3.98; P = .025).
• Koilocytosis occurred more frequently with in situ NSCC (21.6% vs 12.4%, P = .015); older age was associated with lower odds of koilocytosis (OR, 0.949; P < .001). Those with koilocytosis were more often periungual (70.2% vs 59.5%, P = .049) and less often subungual (2.1% vs 13.1%, P = .044) than those without koilocytosis.
• Mohs micrographic surgery (39.5%), local excision (35.3%), and en bloc nail unit excision (32.3%) were the most common treatments; recurrence rates did not significantly differ among surgical approaches, with an overall recurrence rate of 9.7% at a median of 1.9 years.
• High-risk (HR) HPV was detected in 10 of 15 PCR-confirmed HPV-positive tumors (all HPV 16), of which 8 of 10 (80%) were invasive NSCC; low-risk subtypes (HPV 6 and 7) were found in five tumors, of which three were NSCC in situ.

IN PRACTICE:

“NSCC presents as a periungual hyperkeratotic papule/plaque with anteroposterior growth or an ulcerating subungual mass with loss of [nail plate] production, subungual oozing, and dermal invasion,” whereas periungual NSCC is associated with HPV infection, often sexually transmitted, they wrote. “While HPV-related NSCC is often in situ, NSCC associated with HR-HPV subtypes may present with aggressive, invasive disease,” they pointed out, noting that “any warty digital change that is treatment-resistant or atypical for a periungual wart warrants biopsy — especially in immunocompromised patients.”

SOURCE:

The study was co-led by Shari R. Lipner, MD, PhD, and Jose W. Ricardo, MD, Department of Dermatology, Weill Cornell Medicine, New York City, and was published online on May 7 in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The study was retrospective and a multicenter trial with variable reporting and follow-up, limiting causal inference. HPV status relied mainly on histologic koilocytosis because PCR was infrequently performed and genotyping methods were often unavailable, reducing definitive classification. Key data were missing for skin phototype, occupation, prior HPV disease (about 50% were unknown), and koilocytosis, limiting subgroup analyses.

DISCLOSURES:

There was no study funding source. Lipner disclosed serving as a consultant for BelleTorus Corporation and Moberg Pharma. Ricardo and the other co-authors reported having no relevant disclosures.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.