Colp climate module Flashcards
What are the 2 subfamilies of HPV?
Papillomavirinae and Polyomavirinae
Structure of the HPV genome
What are the 3 regions?
- the long control region (LCR) without coding potential
- early proteins (E1-E8)
- late proteins (L1 and L2)
Role of p53 tumour suppressor gene
It promotes cell arrest or apoptosis when activated by unscheduled induction of DNA replication
HPV lifecycle in the cervix
The HPV lifecycle is restricted to the cervical epithelium; there is no viraemia.
The virus is thought to infect the basal cell layer of the epithelium via microabrasions.
It then uses the host cell machinery to replicate viral DNA and express virally encoded proteins.
- Infection of basal cells
- Episomal viral DNA in cell nucleus
- Viral DNA replication
- Viral assembly
- Shedding of virus laden epithelial cells
Early proteins = steps 1-3
Late proteins = step 4
What proportion of HPV cancers do types 16&18 account for?
70%
HPV accounts for __% of these cancers?
- Cervical?
- Anal?
- Vulval/vaginal/penile?
- Oropharyngeal?
99.7% of cervical cancers
90% of anal cancers
40% of vulval, vaginal and penile cancers
12% of oropharyngeal cancers
What proportion of HPV infections lead to cancer?
<2%
What is the lag period between HPV infection and cancer?
15 years
What % of people will acquire HPV over a lifetime?
76%
Vast majority of infections are transient
>5 sexual partners increases risk
Acquisition and clearance rates in women aged 51?
Acquisition rates higher, clearance rates lower
HrHPV types 16 and 18 have highest persistent infection rates
Differences between the innate and adaptive immune system?
Innate immune system:
- Activated by cell death, is not antigen specific, has no memory and its cardinal sign is inflammation.
- Adaptive immune system is antigen specific, builds up memory and has two arms, a humoral arm to produce antibodies and a cellular arm, including T-cell help (TH) for antibody production and cytotoxic T-cells (CTL).
These two systems have a close interaction. The key player in this interaction is the antigen-presenting cell (APC).
The APC bridges innate and adaptive immunity,
How does the APC work?
the APC carries information from the innate to the adaptive immune system and presents two pieces of information to the adaptive immune system:
Firstly, it will present the antigen itself
Secondly, it will transmit information on the type of pathogen the antigen originates from, e.g. whether it is a RNA or DNA-virus, a bacterium, etc… through ‘molecular barcode readers’, the Toll-like receptors
Following stimulation, APCs are activated to become dendritic cells in the lymphoid organs and tissues, where they secrete cytokines and present virus-like particle (VLP) antigens to T-cells.
T-helper cells provide ‘help’ to cytotoxic T-cells (which can lyse virally infected cells) and to B-cells which produce antibodies – important for prevention of viral infection.
T- and B-cells migrate to infected tissues where they perform their respective effector functions and generate immune memory.
How does HPV evade the immune system?
- viral lifecycle occurs entirely within epithelium
- No viraemia
- No cell death
- No inflammation
- Local immunosuppression caused by viral proteins
Typically, after HPV infection how long to develop:
- CIN 1
- CIN 2
- CIN 3
- Cancer
- CIN1: 3 months
- CIN 2: 6 months
- CIN 3: 1-2 years
- Cancer: Typically 10-20 years but can be as fast as 1-2 years
Co-factors that increase the risk of progression to cervical cancer?
- environmental, e.g. smoking
- sexual exposure, e.g. parity, multiple partners, early onset of sex
- hormonal, e.g. long-term use of oral contraceptives
- immunosuppressive, e.g. HIV, transplant recipients
- long-term systemic steroid users
Cervical cancer incidence
the third most common cancer in women and the seventh overall,
More than 85% of the global burden occurs in developing countries where it accounts for 13% of all female cancers.
Necessary requirements for a screening test?
The test needs to be effective
Prevent a significant number of deaths from the disease
Cost effective
Acceptable to patient
Sensitive and specific
Incidence of cervical cancer in Australia?
7 per 100,000
Management if glandular abnormality found?
Refer for colposcopy
Benefits of liquid based cytology over conventional Pap smear?
- lower unsatisfactory rate (in an Australian study the unsatisfactory rate was reported as 3% for conventional smears and 1% for liquid-based cases).
- there is residual material upon which HPV testing may be performed, and that this test may be screened with an imager, which may become increasingly important in a vaccinated population with a lower rate of abnormalities.
Histology of the ectocervix
- covered by stratified squamous epithelium
- The junction of the endocervical glandular mucosa with the squamous epithelium of the squamous epithelium of the ectocervix is called the squamocolumnar junction, which does not always lie at the external os, and is often on the ectocervix.
- The epithelial layers are basal/parabasal, midzone and superficial.
- Upper layers contain glycogen, in response to circulating oestrogens.
Normal original squamous epithelium does not become white after application of acetic acid.
Histology of the endocervix
The endocervical canal:
- lined by a single layer of mucin-secreting epithelium, which blends with the squamous epithelium of the ectocervix, and at the other end, the endometrial epithelium of the isthmus.
Endocervical epithelium dips into elongated clefts in the stroma, referred to as endocervical glands, which are not true glands, but rather clefts.
Benign glandular mucosa often forms villous or processes that are recognizable as such at colposcopy, and often become whiter after application of acetic acid.
