Human Papilloma Virus (HPV)

Subjects: virology, microbiology · Systems: virology, microbiology · Tags: virology, microbiology, HPV, hpv

Basic Virology and Structure

HPV belongs to the Papillomaviridae family. It is a non-enveloped, double-stranded DNA virus with icosahedral symmetry. Because it lacks an envelope, it is quite stable in the environment, reissting drying and mild disinfectsnts. There are over 200 types of HPV, and they are grouped into “low-risk” and “high-risk” strains based on their oncogenic potential. The most clinically important high-risk types are 16 and 18, strongly associated with cervical anogenital, and oropharyngeal cancers. Low-risk types, particularly 6 and 11, cause genital wards and laryngeal papillomatosis, but are rarely associated with malignancy.

Tropism and Life Cycle

HPV has a remarkable preference for basal keratinocytes of stratified squamous epithelium, which it infects through microscopic abrasions in the skin or mucosa. The virus does not cause viremia; instead, it remains confined to the epithelium. Its replication is intimately tied to the differentiation of the keratinocyte:

• In basal cells, the viral genome is maintained as an episome (extrachromosomal)
• As cells differentiate and migrate upward, the virus hijacks the host machinery to produce viral proteins and assemble virions.
• Mature virions are released when infected epithelial cells slough off at the surface, completing the cycle without cell lysis.

This explains why HPV infection often produces warts (benign proliferative lesions of squamous epithelium).

Oncogenesis: The Role of E6 and E7

What makes high-risk HPV types dangerous is their ability to interfere with host cell cycle regulation. Two viral proteins, E6 and E7, are critical:

• E6 binds to and promotes degradation of p53, the “guardian of the genome”, impairing apoptosis and DNA repair.
• E7 binds to and inactivates the retinoblastoma protein (Rb), releasing E2F transcription factors and driving uncontrolled progression into S phase.

Together, these disruptions lead to genomic instability, accumulation of mutations, and risk of malignant transformation. Integration of the viral DNA into the host genome, more common with high-risk strains, enhances the expression of E6 and E7 and accelerates oncogenesis.

Clinical Manifestations

HPV causes a spectrum of disease depending on the viral type:

• Cutaneous warts: Common warts on hands and feet (Types 1, 2, 4).
• Anogenital warts (condylomata acuminata): Exophytic, cauliflower-like lesions, usually caused by types 6 and 11. These are benign but often recurrent.
• Respiratory papillomatosis: Warts in the respiratory tract (Types 6 and 11), particularly in children born to infected mothers.
• Cervical intraepithelial neoplasia (CIN) and carcinoma: Most strongly linked to types 16 and 18, but also 31, 33 and others. The process begins with low-grade dysplasia (CIN I) and may progress to high-grade (CIN II/III) and invasive cancer if persistent.
  • Other cancers: HPV is implicated in anal, vulvar, vaginal, penile, and oropharyngeal cancers.

Diagnosis and Screening

Most HPV infections are transient and asymptomatic, cleared by the immune system within 1-2 years. The major concert is persistent infection with high-risk types. Pap smear cytology remains a cornerstone of screening: koilocytes (squamous epithelial cells with perinuclear halos and irregular nuclei) are a cytopathic hallmark of HPV. Increasingly, HPV DNA testing is used alongside cytology, especially in women over 30, to identify high-risk infections.

Prevention and treatment

There is nos pecific antiviral therapy for HPV. Warts may be treated with cryotherapy, salicylic acid, or surgical removal, but recurrence is common. The most powerful tool is vaccination. The current vaccines (such as Gardasil 9) cover HPV 6, 11, 16, 18, and several other oncogenic types. They are based on virus-like particles (VLPs) made of the L1 capsid protein, which induce strong neutralizing antibody responses but contain no viral DNA, so they are non-infectious. Vaccination is recommended for both males and females, ideally before sexual debut, as it prevents initial infection but does not clear established infection.

Immunity

Natural infection induces a relatively weak immune response because HPV remains localized to epithelium and avoids systemic exposure. This is why reinfections and persistent infections are common. The vaccine, by contrast, elicits a much stronger systemic neutralizing antibody response.

Summary

HPV is a small, non-enveloped DNA virus that infects squamous epithelium and relies on host cell differentiation to complete its life cycle. Low-ris types cause warts, while high-risk types (notably 16 and 18) predispose to malignancy through E6 and E7-mediated inactivation of tumor suppressors. Screening with Pap smears and HPV DNA testing identigies precancerus changes, while vaccination offers effective primary prevention.

Disclaimer: For education only. Not medical advice; always follow your institution's guidance.