HPV is a small, non-enveloped virus with double-stranded DNA and an icosahedral capsid containing two structural proteins, L1 and L2. High risk HPV types 16 and 18 can cause cervical cancer by integrating their DNA into host cells and overexpressing the E6 and E7 oncoproteins, which inactivate tumor suppressors and promote cell cycle progression. HPV is transmitted through skin-to-skin contact and causes genital warts, cervical cancer, and other anogenital cancers but often has no visible symptoms for years.

1. Structure
 Small, non enveloped
 Icosahedral DNA
 Double-stranded DNA
 Capsid contains two structural
proteins — L1 and L2

2. Human Papilloma virus
 Papilloma viruses were the first to be implicated in the etiology of any
human tumour.
 At least 70 genetically distinct types of HPV have been identified.
 Papilloma viruses are implicated in the etiology of following benign and
malignant tumours :
 HPV types 1,2,4 and 7 cause benign squamous papillomas
(warts) in humans.
 HPV types 6 and 11 genital warts (condyloma acuminata).
Genital warts have low malignant potential.
 HPV types 16 and 18 squamous cell carcinoma of the cervix and
anogenital region.

3. Mode of Transmission
 HPV is transmitted through intimate skin-to-skin contact
 It is most commonly spread during vaginal or anal sex.
 It can be passed even when an infected person has no signs or symptoms.
 It can develop symptoms years after being infected, making it hard to know when
you first became infected.

4. HPV Oncogenesis
 On persistence of infection with high risk HPV types, the viral DNA is integrated
into the target epithelial cells.
 This results in genomic instability of the host cell leading to loss of E2 viral
repressor and overexpression of viral oncoproteins E6 and E7.
 These oncoproteins (E6 and E7) from high risk HPVs have high affinity for target
hosts cell than these oncoproteins from low risk HPVs.
 Transforming effects of HPV are largely due to alteration in genes encoding E6 and
E7 oncoproteins as followings :

5. HPV-E6 Degrades TP53 Blocks apoptosis TERT overexpressed
(Tumor- suppressor
inhibited)
HPV-E7 Binding to RB Inactivates p21, p27 Activates cyclin D, C,CDK4
(RB- E2F
Displaced)
(CDK Inhibiters)
Oncogenic Effects of E6
Oncogenic Effects of E7
• Immortalization
• Excessive proliferation
• Genomic instability
• Immortalization
• Excessive proliferation
• Genomic instability

6.  To summarise, high risk HPV types express oncogenic proteins that inactivates
tumour suppressors, activate cyclins, inhibit apoptosis and combat cellular
senescence.
 Thus it is evident that HPV proteins promote many of the hallmarks of cancer.
 The primacy of HPV infection in the causation of cervical cancer is confirmed by the
effectiveness of HPV vaccines in preventing cervical cancer.

7.  In addition to transforming effects of E6 and E7 oncoproteins derived from
high risk HPVs, a few factors play role in development of cervical cancer.
 These include :-
1. Immunosuppression
2. Cigarette smoking
3. Other coexisting infections
4. Hormonal changes
5. Dietary deficiencies

8. Diagnosis
 The important methods to diagnose HPV infection are:
 Colposcopy and acetic acid test
 Biopsy
 DNA test (PCR, Southern Blot Hybridization, In Situ Hybridization)
 Pap smear

9. Prevention
 Avoid skin-to-skin contact by not having sex with strangers.
 Use condoms and/or dental dams every time.
 Vaccination :
 Three vaccines are available to prevent infection by some HPV types.
 All protect against initial infection with HPV types 16 and 18, which cause most of the HPV-
associated cancer cases.
i. Gardasil:
i. quadrivalent vaccine
ii. protects against HPV types 6 and 11, which cause 90% of genital warts.
ii. Cervarix:
i. bivalentis
ii. prepared from virus-like particles (VLP) of the L1 capsid protein.
iii. Gardasil 9:
i. non-avalent
ii. it has the potential to prevent about 90% of cervical, vulvar, vaginal, and anal cancers.