Clinical spectrum of penile intraepithelial neoplasia in a sexual health service: a retrospective case series.

BACKGROUND

Penile intraepithelial neoplasia (PeIN) is an uncommon precursor to invasive penile squamous cell carcinoma (SCC). Its heterogeneous appearance may overlap with inflammatory penile dermatoses, genital warts, or infection, potentially delaying diagnosis. We aimed to characterise the clinical spectrum, inflammatory context, biopsy triggers, histopathology, management, and outcomes of histopathologically confirmed PeIN presenting to a sexual health service.

METHODS

We conducted a retrospective case series of patients with histopathologically confirmed low-grade or high-grade squamous intraepithelial lesions, or invasive SCC, assessed at Melbourne Sexual Health Centre, Australia, from 2018-2025. Electronic records were reviewed for demographics, immune status, circumcision status, lesion site and morphology, symptoms, coexisting inflammatory disease, biopsy indications, histopathology, treatment, recurrence, and follow-up. Data were analysed descriptively.

RESULTS

Thirteen patients aged 25-72 years were identified; four had lichen sclerosus and three had immunosuppression or immune-modifying therapy. Most were uncircumcised at diagnosis. Lesions predominantly involved the glans or inner foreskin, but also occurred on the shaft, and showed marked heterogeneity, including erythematous or white plaques, papules, warty or hyperkeratotic lesions, erosions, fissures, and ulcerated nodules. Symptoms ranged from none to pain, burning, itch, hypersensitivity, malodour, and non-healing sores. Several lesions initially appeared inflammatory or wart-like; sometimes in the setting of documented lichen sclerosus. Biopsy was generally prompted by persistence, focal hyperkeratosis or induration, ulceration or erosion, architectural change, progressive enlargement, or incomplete response to empiric therapy. Histopathology showed predominantly high-grade lesions; one patient had low-grade disease with biopsy-confirmed recurrence, and two had invasive SCC. All cases were HPV-associated by reported histopathological features and/or p16 positivity. Management was frequently multimodal and multidisciplinary, including circumcision, local or wide excision, partial penectomy, imiquimod, 5-fluorouracil, cryotherapy, and treatment of coexisting inflammation. Outcomes were generally favourable where documented, although recurrence or suspected recurrence occurred in some patients and ongoing surveillance was often required.

CONCLUSIONS

PeIN presenting to sexual health services is clinically diverse and commonly embedded within an inflammatory clinical narrative. Persistent or atypical penile lesions, particularly those showing focal change or incomplete treatment response, warrant a low threshold for biopsy and coordinated dermatology-urology management.