What is the appropriate evaluation and treatment for a 45-year-old male presenting with a penile rash and warts, potentially indicating sexually transmitted infections (STIs), including human papillomavirus (HPV) and human immunodeficiency virus (HIV)?

Evaluation and Treatment of Penile Rash and Warts in a 45-Year-Old Male

For a 45-year-old male presenting with penile warts, the primary treatment goal is removal of visible warts to alleviate symptoms, not HPV eradication, and comprehensive STI screening including HIV testing is mandatory given the high co-infection rates. 1

Immediate Evaluation

STI Screening Panel

• Test for HIV, syphilis, gonorrhea, and chlamydia in all patients presenting with genital warts, as co-infection rates are substantial 1, 2
• Obtain genital scrape samples from the glans penis and coronal sulcus for HPV DNA testing if diagnosis is uncertain 2
• Screen for hepatitis B virus, as vaccination may be indicated if non-immune 1
• Consider testing for Trichomonas vaginalis and other STIs based on sexual history 2

Clinical Assessment

• Examine the entire anogenital region including perianal area, as warts can occur at multiple sites 1
• Differentiate external genital warts from intra-anal warts (the latter suggests receptive anal intercourse) 1, 3
• Assess wart characteristics: size, number, location, and morphology to guide treatment selection 1
• Biopsy any atypical lesions to rule out squamous cell carcinoma in situ, particularly if the patient is immunocompromised 1

Treatment Options

Patient-Applied Therapies (Preferred for Motivated Patients)

Podofilox 0.5% solution or gel is the most effective patient-administered option 1, 4:

• Apply twice daily for 3 days, followed by 4 days off therapy
• Repeat cycle up to 4 times as necessary
• Total wart area treated should not exceed 10 cm², total volume ≤0.5 mL/day
• Provider should demonstrate proper application technique at first visit 1

Imiquimod 5% cream is an alternative immune-modulating therapy 1, 5:

• Apply 3 times weekly at bedtime for up to 16 weeks
• Wash treatment area with soap and water 6-10 hours after application 5
• Continue until complete wart clearance or maximum 16-week period 1, 5
• Common side effects include erythema, erosion, and local irritation 5

Provider-Administered Therapies

Cryotherapy with liquid nitrogen offers excellent safety profile 1, 4:

• Efficacy rate of 63-88% with repeat applications every 1-2 weeks 1, 4
• Particularly effective for warts on moist surfaces and intertriginous areas 1

Surgical removal provides highest single-visit efficacy at 93% 4:

• Options include tangential scissor excision, shave excision, curettage, or electrosurgery 1
• Best for patients with large numbers or extensive wart areas 4
• Recurrence rate approximately 29% 4

Trichloroacetic acid (TCA) or bichloroacetic acid (BCA) 80-90% 1:

• Apply small amount only to warts, allow to dry until white "frosting" develops
• Powder with talc or sodium bicarbonate to remove unreacted acid
• Repeat weekly as necessary 1

Treatment Considerations and Common Pitfalls

Expected Outcomes

• Most genital warts respond within 3 months of therapy, but no treatment eradicates HPV infection 1
• Recurrence rates are high (at least 25% within 3 months) with all treatment modalities 1
• Change treatment modality if no substantial improvement after complete course or if severe side effects occur 1
• If left untreated, 20-30% of warts resolve spontaneously within 3 months 6, 7

Special Considerations for HIV-Positive Patients

• HIV-infected men may not respond as well to therapy and experience more frequent recurrences 1, 7
• Higher risk for squamous cell carcinomas arising in or resembling genital warts 1, 7
• Anal HPV prevalence is significantly higher in HIV-positive men, particularly MSM 8, 3
• Consider more aggressive surveillance and earlier biopsy of atypical lesions 1

Critical Patient Counseling Points

Transmission and Infectivity

• Genital warts can be transmitted even when no visible warts are present and even after treatment 6
• Most sexual partners are likely already subclinically infected by the time of diagnosis 1, 6
• Patients should refrain from sexual activity until warts are removed, though duration of infectivity after treatment is unknown 6
• Condoms reduce but do not eliminate transmission risk, as HPV can infect areas not covered by condoms 6, 7

Partner Management

• Sex partners do not require routine examination unless they have visible warts or desire evaluation 1
• HPV tests should not be used to screen male partners, as no clinically validated HPV test exists for men 6
• Both partners should be screened for other STIs 6
• HPV diagnosis does not indicate sexual infidelity, as the virus can remain dormant and reactivate years after initial infection 6, 7

Long-Term Implications

• Treatment may reduce transmission by "debulking" visible warts, though this is not definitively proven 1
• HPV may persist in surrounding normal tissue even after wart removal 1
• Most recurrences result from reactivation of subclinical infection rather than reinfection 7

Follow-Up Protocol

• Schedule follow-up evaluation 3 months after treatment to monitor for recurrences 1
• Earlier visits may be useful to document wart-free state, monitor treatment complications, and provide ongoing education 1
• For HIV-positive patients, establish regular surveillance protocol given higher recurrence rates and malignancy risk 1, 7

Prevention Strategies

• Quadrivalent HPV vaccine (Gardasil) is recommended for males aged 9-26 years, even if already diagnosed with HPV 7
• Vaccine prevents infection with HPV types 6 and 11 (causing 90% of genital warts) and high-risk types 16 and 18 7
• Emphasize consistent condom use for future sexual encounters to reduce transmission to uninfected partners 1, 6