1. WHAT IS HPV? – THE MOST IMPORTANT FACTS

• DNA virus → double-stranded, circular, non-enveloped,icosahedral
• Family: Papillomaviridae.
• >200 types identified.
• Epithelial tropism → infects basal keratinocytes of skin/mucosa.

📌 Why non-enveloped matters?

→ Resistant to heat, drying, detergents → survives on fomites & skin → easy transmission.

2. HIGH-RISK vs LOW-RISK TYPES (SUPER IMPORTANT)

High-risk oncogenic types (cause cancer)

• HPV 16 → highest risk (50–60% of cervical cancers)
• HPV 18 → second highest
• Others: 31, 33, 45, 52, 58

💥 Causes:

• Cervical cancer (squamous + adenocarcinoma)
• Vulvar/vaginal cancer
• Anal cancer
• Penile cancer
• Oropharyngeal cancer

Low-risk (non-oncogenic) types

• HPV 6, 11
• Cause genital warts (condyloma acuminata)
• Also laryngeal papillomatosis in infants

3. STRUCTURE & GENES (THE KEY EXAM POINT)

HPV genome has early (E) and late (L) proteins.

Early proteins (E1–E7)

• E6 → destroys p53 tumor suppressor
• E7 → inactivates Rb tumor suppressor
• E5 → enhances HPV replication

❗ THIS IS THE MOST EXAM-TESTED MECHANISM

Disruption of p53 & Rb → uncontrolled cell cycle → dysplasia → CIN → cancer.

Late proteins (L1, L2)

• L1 = major capsid protein → used in vaccines (recombinant L1 VLPs)
• L2 = minor capsid protein

💡 Vaccines use L1 VLP = no DNA = cannot cause infection.

4. HOW HPV INFECTS CELLS (PATHOGENESIS)

1. Requires microscopic break in epithelium
2. Virus infects basal cell layer
3. Viral replication occurs as cells differentiate toward surface
4. Persistent high-risk infection → E6/E7 overexpression → CIN2/3 → carcinoma

⏳ Persistent infection = biggest risk factor

✔ Smoking, HIV, immunosuppression worsen persistence.

5. HISTOPATHOLOGY (VERY HIGH-YIELD)

Koilocytes

• Hallmark of HPV infection
• Features:
• Enlarged nucleus
• Perinuclear halo
• Irregular nuclear membranes

📌 Seen in:

• LSIL
• Condyloma acuminata

6. TRANSMISSION

• Sexual contact (most common)
• Skin-to-skin genital contact
• Vertical: mother → baby → laryngeal papillomatosis
• Fomites (rare)

💡 Condom reduces but does NOT eliminate risk.

7. HOW HPV CAUSES CANCER – THE ESSENTIAL 3-STEP PROCESS

1. Persistent infection with high-risk types
2. Integration of viral DNA into host genome
3. E6/E7 oncogene overexpression
• E6 → p53 degradation
• E7 → Rb inactivation

📌 Results → CIN → CIS → invasive carcinoma.

8. HPV TESTING (OBGYN EXAM GOLD)

• DNA testing for high-risk types (e.g., HPV 16/18)
• Types:
• HPV DNA Test
• mRNA E6/E7 test
• Used for:
• Screening (≥30 years)
• Triage after abnormal cytology
• Post-treatment surveillance

9. CYTOLOGY FINDINGS

• LSIL (CIN1) → koilocytes
• HSIL (CIN2/3) → increased N:C ratio, abnormal mitoses
• ASC-US → unclear atypia

10. HPV VACCINES (EXAM-FAVORITE)

Gardasil-9 (most used): covers

6, 11, 16, 18, 31, 33, 45, 52, 58

Previous versions:

• Gardasil (6, 11, 16, 18)
• Cervarix (16, 18)

Vaccine characteristics:

• Recombinant L1 VLP
• Non-infectious, non-oncogenic
• IM injection
• 2- or 3-dose schedules depending on age

✔ Prevents >90% cervical cancers

✔ Prevents genital warts (6 & 11)

11. IMMUNITY

• Infection does NOT give long-lasting immunity
• Reinfection possible
• Vaccine gives stronger immunity than natural infection.