Human Papilloma Virus (HPV)

• Human Papilloma Virus (HPV) is a double-stranded, non-enveloped, circular DNA virus.
• HPV spreads occurs through direct sexual contact with genital warts (condyloma acuminata).
• Nonsexual transmission occurs through plantar warts, contaminated surfaces, and during birth if the mother has genital warts.
• This can lead to warts in the infant's mouth and respiratory tract, especially laryngeal papillomas.
• Asymptomatic shedding contributes to HPV transmission.
• Immunocompromised individuals are at higher risk, developing extensive warts and cervical carcinoma due to dysplasia and neoplasia.
• HPV infects squamous epithelial cells, leading to abnormal cell development known as koilocytes.
• Viral proteins E6 and E7 interfere with tumor suppressor genes p53 and retinoblastoma (Rb).
• HPV-16 and HPV-18 have E6 and E7 proteins that bind more strongly to p53 and Rb, increasing the risk of carcinoma.
• Cell-mediated immunity and antibodies help control wart spread.
• HPV-16 and HPV-18 are major causes of cervical carcinoma through intraepithelial neoplasia.
• HPV causes benign plantar and genital warts, which are common.
• Anal and penile warts can progress to cancer, but this is rare.
• 96% of genital warts are caused by HPV-6 and HPV-11.
• The incubation period for HPV is typically 3-4 months.
• Mild dysplasia caused by HPV spontaneously regresses in 40-70% of cases..
• HPV causes mild cervical intraepithelial neoplasia (CIN I) to moderate (CIN II), which can develop over 1-4 years.

Diagnosis

• Diagnosed through pap smear histology, which reveals koliocytic squamous epithelial cells in papanicolaou stained smears.
• HPV does not grow in cell culture, so culturing is not useful for diagnosis.
• HPV antibody tests are rarely used.
• DNA molecular probes, PCR, and RT-PCR are used for diagnosis.

Treatment

• Spontaneous regression of HPV warts is possible but can take months or years.
• Warts are often removed to alleviate pain and discomfort, for cosmetic reasons, and to prevent further spread.
• Removal methods include surgical cryotherapy, electrocautery, chemical removal using podophyllin, and surgical removal for laryngeal papilloma.
• Recurrence of warts after treatment is common.
• Medications can stimulate innate and inflammatory responses, such as imiquimod (Aldara) and interferon, to promote healing.
• Topical or intralesional cidofovir can be used to kill HPV-infected cells.
• Pathogenesis of HPV involves the virus entering parasitic maternal cells and inducing a perinuclear cytoplasmic vacuole, creating koilocytes.
• E6 and E7 viral genes interfere with the activity of tumor suppressor genes P53 and RB, contributing to oncogenesis.

Transmission of HPV

• Genital warts are a common sexually transmitted disease.
• HPV resists inactivation and is transmitted on fomites like furniture and bathroom tools.
• Infection occurs through direct contact with small breaks in the skin or mucosa.
• An infected mother can transmit HPV to her neonate during birth, causing warts in the mouth and respiratory tract.
• The appearance of warts depends on the HPV type and the infected site.
• Condylomata acuminata occur on the external genitalia and perianal areas.
• These lesions are caused mostly by HPV types 6 and 11.
• Anal and penile warts can progress to cancer if caused by high-risk oncogenic strains like HPV 16 and 18.

Cervical Dysplasia and Neoplasia

• Infection of the female genital tract by high-risk HPV types is linked to intraepithelial cervical neoplasia and cancer.
• Initial neoplastic changes are termed dysplasia.
• Approximately 40 to 70% of mild dysplasia spontaneously regress.
• Cervical cancer develops through progressive cellular changes from mild to moderate to severe neoplasia.
• Regular pap smears aid in early detection.