Penile Cancer: Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Penile cancer is a rare malignancy arising predominantly from the squamous epithelium of the glans penis and prepuce (foreskin), with less frequent involvement of the penile shaft. It represents less than 1% of male cancers in developed nations, but accounts for up to 5-10% of male malignancies in parts of Sub-Saharan Africa, South America (particularly Brazil), and some Asian countries where penile cancer is endemic. Globally, approximately 36,000 new cases are diagnosed annually. Squamous cell carcinoma (SCC) constitutes over 95% of penile malignancies; rare subtypes include verrucous carcinoma, sarcomatoid carcinoma, adenocarcinoma, and melanoma. HPV infection — particularly HPV-16 — drives approximately 50% of penile SCC through mechanisms similar to cervical cancer. Penile intraepithelial neoplasia (PeIN) is the recognized precursor lesion. Inguinal lymph node metastasis is the most important prognostic determinant — approximately 60% of patients have clinically palpable inguinal lymph nodes at diagnosis, though not all represent malignant involvement (some are inflammatory).

HPV infection — principally HPV-16, and less commonly HPV-18 and other high-risk genotypes — is detected in approximately 50% of penile SCC tumors and is the dominant etiological driver in HPV-positive cases. HPV-positive penile cancers tend to arise in younger patients and may have a more favorable prognosis. The most important non-HPV risk factors are phimosis (inability to retract the foreskin, which creates a chronically moist environment promoting chronic inflammation and carcinogen accumulation), poor genital hygiene, and chronic inflammatory conditions including lichen sclerosus and lichen planus. Cigarette smoking doubles the risk of penile SCC, particularly for HPV-negative tumors, through direct carcinogenic effect on squamous epithelium. Absence of circumcision confers elevated risk, particularly in the setting of phimosis. Penile intraepithelial neoplasia (PeIN) — including erythroplasia of Queyrat (carcinoma in situ of the glans) and Bowen disease of the penis — are recognized precursor lesions with significant malignant transformation potential.

Penile cancer most often presents as a painless or mildly painful lesion on the glans or prepuce that fails to heal despite topical treatments. The lesion may appear as a non-healing ulcer, an exophytic (outwardly growing) wart-like mass, an indurated (hardened) plaque, or a nodular growth with overlying skin changes. The prepuce may conceal the primary lesion when phimosis is present, leading to diagnostic delay when the penis cannot be fully examined. Secondary infection with purulent or blood-stained discharge is common. Inguinal lymphadenopathy — often initially bilateral from inflammatory changes related to secondary infection rather than malignant involvement — is present in approximately 60% of patients at diagnosis. Penile pain, erection difficulties, urinary obstruction (meatal involvement), or bleeding are additional signs. Advanced local disease produces tumor fixation, perineal involvement, or fistula formation. Diagnostic delay due to patient embarrassment remains a persistent problem and negatively affects outcomes.

Punch or incisional biopsy of the primary penile lesion establishes histological diagnosis, including SCC subtype, grade, and depth of invasion. MRI of the penis (with artificial erection using intracorporeal alprostadil injection) is the gold standard for local tumor staging, assessing invasion of the corpora cavernosa and spongiosum — T staging that directly guides surgical approach and determines eligibility for organ-sparing procedures. Inguinal node assessment combines clinical palpation with ultrasound-guided fine-needle aspiration cytology of suspicious nodes. Dynamic sentinel lymph node biopsy (DSNB) using intratumoral technetium-labeled nanocolloid injection with lymphoscintigraphy and gamma probe-guided excision is the standard for clinically node-negative high-risk patients. CT of the chest, abdomen, and pelvis detects distant metastases (liver, lung, bone). HPV genotyping and p16 IHC are performed on all specimens. AJCC 8th edition TNM staging is applied.

Organ-preserving surgery is strongly preferred for early-stage (T1-T2) penile cancer to preserve sexual function, urinary continence, and body image. Options include: glansectomy with or without resurfacing for glans-confined tumors; partial penectomy for shaft-involving tumors with adequate residual penile length; laser ablation (CO2 or Nd:YAG) for superficial lesions and carcinoma in situ; and Mohs micrographic surgery for selected cases. Total penectomy with perineal urethrostomy is required for large T3-T4 tumors or extensive urethral involvement. Negative surgical margins are the paramount oncological criterion for any surgical approach. Inguinal lymph node dissection (ILND — template radical or modified) is performed for node-positive disease; adjuvant cisplatin-based chemotherapy is used for pN2-3 pathological nodal disease. Definitive radiotherapy (external beam or brachytherapy) is an alternative to surgery for glans-confined tumors in selected patients wishing to avoid surgery. Neoadjuvant TIP chemotherapy (paclitaxel-ifosfamide-cisplatin) for initially unresectable node-positive disease can enable subsequent surgical clearance in approximately 40-50% of patients. Pembrolizumab is under investigation for advanced disease.

HPV vaccination with Gardasil 9 — administered in adolescence before HPV exposure — can prevent the approximately 50% of penile cancers attributable to HPV infection. Boys and men up to age 26 are routinely recommended HPV vaccination, with shared decision-making up to age 45. Neonatal circumcision eliminates phimosis as a risk factor and substantially reduces penile cancer risk, particularly in populations where circumcision is not routine. Good genital hygiene and regular cleaning under the foreskin reduces chronic inflammatory carcinogen accumulation. Patients with phimosis should seek urological treatment (topical steroid therapy or circumcision) before chronic inflammation progresses to malignant change. Known premalignant lesions — lichen sclerosus, PeIN, erythroplasia of Queyrat — require regular dermatological or urological follow-up with biopsy of any suspicious change. Tobacco cessation is important for HPV-negative penile cancer prevention.

Any man who notices a new growth, sore, ulcer, or indurated plaque on his penis — regardless of whether it is painful or painless — that fails to heal within 2-3 weeks must seek urgent medical evaluation and biopsy referral. Penile cancer is one of the few cancers where patient delay (due to embarrassment) commonly causes the difference between organ-preserving surgery and total penectomy. A painless inguinal (groin) lump that persists after a short course of antibiotics should be evaluated urgently with ultrasound and FNAC. Men with phimosis preventing adequate penile examination should inform their urologist of any new symptoms and arrange examination under anesthesia if necessary. Any man with lichen sclerosus, PeIN, or a prior penile skin lesion should maintain regular dermatological surveillance. Symptoms of urinary obstruction combined with a penile lesion represent a particularly urgent situation requiring same-day evaluation.

Stage I/II (T1-T2, N0): 5-year survival approximately 85%. N1-2 (single or multiple inguinal node metastasis): approximately 50%. N3 (pelvic nodes, extranodal extension) or distant metastasis: less than 20%. Inguinal lymph node status is the single most powerful prognostic factor. HPV vaccination in adolescents is expected to significantly reduce future penile cancer incidence. The prognosis for Penile Cancer: Causes, Symptoms, Diagnosis and Treatment varies depending on severity at diagnosis, the patient's overall health, and how promptly treatment is initiated. With early diagnosis and appropriate management, many patients achieve good outcomes and maintain quality of life. Regular follow-up with healthcare providers is essential to monitor progress, adjust treatment as needed, and detect any complications early. Adherence to prescribed treatments and lifestyle modifications significantly improves long-term prognosis.