HPV (Human Papillomavirus) - Symptoms & Clinical Presentation

Overview

1. Genital Warts (Condyloma Acuminata) - Low-Risk HPV Types 6 & 11

• Soft, sessile lesions that appear flat or cauliflower-like (exophytic)
• Small, skin-colored or pink growths; can range from solitary 1-2 mm papules to large clusters
• Flat condyloma appear as white, plaque-like growths
• In intertriginous (moist) areas, warts may have a moist appearance

• In women: vulva, vaginal introitus, vagina, labia, cervix, perineum
• In men: shaft of the penis, foreskin, glans
• Both sexes: perianal skin, anal canal, urethra

• Usually asymptomatic
• Itching (pruritus)
• Burning or tenderness
• Bleeding - especially with anal lesions
• Discharge
• Pain
• Large lesions can interfere with defecation, intercourse, or vaginal delivery

Anal condyloma acuminata - Current Surgical Therapy 14e

2. Cervical Disease - High-Risk HPV Types 16 & 18

• Early: No symptoms - detected only by Pap smear/cervical cytology
• Cervical intraepithelial neoplasia (CIN): asymptomatic, found on screening
• Advanced cervical cancer: abnormal vaginal bleeding, post-coital bleeding, pelvic pain, discharge

3. Anal & Rectal Disease

• Most common presenting symptoms of anal squamous cell carcinoma (SCC): rectal bleeding and sensation of a mass
• Anal warts may cause pruritus, pain, or bleeding
• Larger lesions can cause anal canal stricture

4. Cutaneous (Skin) Warts - Non-Genital HPV Types

• Small, rough, raised skin growths
• White, beige, or brown colored
• Usually painless unless on pressure-bearing areas (plantar warts on feet can be painful)

5. Respiratory Papillomatosis

• Caused by HPV types 6 and 11 (likely from intrapartum transmission through an infected birth canal)
• Can cause hoarseness, voice changes, or breathing difficulty depending on location and extent

6. Oropharyngeal/Head & Neck Disease

• HPV-associated oropharyngeal cancers (especially HPV-16) present with:
  • Sore throat, difficulty swallowing
  • Neck mass (lymph node enlargement)
  • Ear pain
  • These cancers are rising in incidence, particularly in men

Key HPV Type Summary

Important Notes

• Most infections are asymptomatic and resolve without treatment within 1-2 years
• External condyloma (genital warts) is not directly associated with cervical dysplasia, but patients with genital warts are at risk for co-infection with multiple HPV subtypes and still require routine cervical cancer screening
• In immunocompromised patients (e.g., HIV), lesions are often multiple, coalescent, extensive, and more treatment-resistant, with accelerated development of HPV-associated carcinomas
• Diagnosis is clinical; 5% acetic acid application turns lesions white, aiding identification

Prevention

Skin Warts (Verrucae)

Types of Skin Warts

1. Verruca Vulgaris (Common Warts)

• Caused by: HPV types 1, 2, 4, 7, 27, 29, 57
• Appearance: Dome-shaped, rough, keratotic papules with a firm, irregular surface
• Location: Dorsal hands, fingers, other extremities; periungual (around nails)
• Characteristic sign: Punctate black dots = thrombosed capillaries (often called "seed warts" - a misnomer)
• Symptoms: Usually painless; can be tender if traumatized

2. Plantar Warts (Verruca Plantaris)

• Caused by: HPV types 1, 2, 4
• Appearance: Surrounded by hyperkeratotic, callus-like skin; grow inward due to pressure
• Location: Soles of feet, weight-bearing surfaces
• Symptoms: Often painful on walking and pressure
• Key diagnosis sign: Paring away the callus reveals small, punctate bleeding points - nearly pathognomonic for HPV
• Mosaic warts: Multiple plantar warts that merge into one large lesion

3. Flat Warts (Verruca Plana)

• Caused by: HPV types 3, 10, 28, 49
• Appearance: Smooth, small (1-4 mm), flesh-colored, slightly raised papules - flat-topped
• Location: Face, legs (spread easily by scratching or shaving)
• Behavior: Inconspicuous at first but can propagate rapidly, sometimes into the hundreds

4. Filiform Warts

• Appearance: Long, narrow, finger-like projections on a narrow stalk
• Location: Face (around eyes, nose, lips), neck
• Symptoms: Usually asymptomatic; can be cosmetically bothersome

5. Mosaic Warts

• A cluster of warts that fuse together into a single large plaque
• Most often seen on palms or soles

Natural History

• Many warts do not resolve spontaneously - only about 40% clear within 2 years without treatment
• HPV is never fully eliminated from the body; the immune system keeps it in remission (like herpes)
• Warts can remain dormant for months, then suddenly multiply
• Immunosuppressed patients (HIV, transplant recipients) have more extensive, treatment-resistant warts

Differential Diagnosis

• Seborrheic keratosis
• Actinic keratosis
• Molluscum contagiosum
• Corn or callus (plantar location)
• Nevus (mole)
• Cutaneous dysplasia / squamous cell carcinoma

For plantar lesions: after paring, punctate bleeding points confirm wart diagnosis. Biopsy when diagnosis is uncertain.

When to Treat

• Pain or bleeding
• Rapid growth or spread
• Psychosocial concern / cosmetic distress
• Employment impact (e.g., food handlers)
• Immunosuppressed patients (higher malignancy risk)
• HPV has been found in 31% of squamous cell carcinomas and 36% of basal cell carcinomas even in non-immunosuppressed patients

Treatment Options

• Salicylic acid has the strongest evidence - requires consistent application for up to 12 weeks
• Cryotherapy is commonly used - repeat every 3-4 weeks as needed
• Candida antigen injection has moderate evidence for recalcitrant warts