Human Papillomavirus
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Direct answer
Human papillomavirus is a small, non-enveloped, double-stranded DNA virus that infects squamous epithelium and causes almost all cervical cancers. Types 16 and 18 are the high-risk types behind about 70 per cent of those cancers, while types 6 and 11 cause most genital warts. Its oncogenic effect rests mainly on the E6 and E7 proteins, which inactivate p53 and retinoblastoma protein.
What you must remember
- Structure: Icosahedral, non-enveloped capsid enclosing a circular double-stranded DNA genome of about 8 kilobases.
- High-risk types: Types 16 and 18 dominate, with 31, 33, 45, 52 and 58 contributing further cancers.
- Low-risk types: Types 6 and 11 cause anogenital warts (condylomata acuminata) and recurrent respiratory papillomatosis.
- Oncoproteins: E6 promotes degradation of p53, and E7 binds retinoblastoma protein to release E2F and drive cell division.
- Koilocytes: Enlarged, wrinkled nuclei with a perinuclear halo on cervical cytology signal productive HPV infection.
- Culture: HPV cannot be grown in routine culture, so diagnosis depends on DNA detection by PCR or hybrid capture.
- Vaccines: Prophylactic L1-based vaccines prevent infection with covered types and are most effective before sexual debut.
From infection to invasive cancer
Cervical cancer develops over years through a sequence of viral and host events. Each step is a point where screening or vaccination can interrupt the process.
- Entry through micro-injury: The virus reaches basal keratinocytes through tiny breaks in the epithelium, and the cervical transformation zone is the most vulnerable site.
- Episomal replication: The viral genome persists as an episome in dividing basal cells, and productive infection is confined to the upper epithelial layers.
- Oncoprotein action: E6 and E7 disable p53 and retinoblastoma protein, so cells with DNA damage keep dividing rather than undergoing apoptosis or arrest.
- Integration into the host genome: In high-grade lesions the viral DNA often integrates and disrupts the E2 gene, removing its brake on E6 and E7 expression.
- Progression through CIN grades: CIN1 frequently regresses, whereas CIN3 carries a meaningful risk of progressing to invasive carcinoma if untreated.
- Clearance or persistence: Most infections clear within one to two years, and only persistent high-risk infection leads to cancer.
Where the exam tries to catch you
HPV questions often test which types cause which disease, and what the vaccine can and cannot do.
- Trap: Naming types 16 and 18 as the cause of genital warts. Correct: Types 6 and 11 cause most warts, while 16 and 18 are the high-risk types that cause cancer.
- Trap: Confirming HPV by culture or serology in routine practice. Correct: HPV is detected by PCR or hybrid capture for its DNA, with cytology providing the koilocyte clue.
- Trap: Expecting the vaccine to treat an established infection. Correct: The prophylactic vaccine prevents infection with covered types and does not clear existing infection or lesions.
Frequently asked questions
Which HPV types cause most cervical cancers?
HPV types 16 and 18 cause about 70 per cent of cervical cancers worldwide. High-risk types 31, 33, 45, 52 and 58 account for a further share, which is why nonavalent vaccines cover them.
Which HPV types cause genital warts?
HPV types 6 and 11 cause the large majority of anogenital warts, also called condylomata acuminata. These low-risk types rarely progress to cancer, although they can cause recurrent respiratory papillomatosis.
Why are koilocytes important in cervical cytology?
Koilocytes are squamous cells with a perinuclear halo and an enlarged, wrinkled nucleus produced by productive HPV infection. Their presence on a Pap smear is a morphological clue to HPV infection and prompts further evaluation.
What is visual inspection with acetic acid used for?
Visual inspection with acetic acid (VIA) is a low-cost screening test for cervical precancer. It is well suited to resource-limited settings, and India's national cancer programme recommends it as a screening tool.
At what age is HPV vaccination most effective?
HPV vaccination is most effective before the first sexual exposure, which is why standard schedules target girls around 9 to 14 years. The vaccine prevents infection with the covered HPV types and does not treat existing lesions.