Lec 37 HPV Flashcards
(48 cards)
What are low risk HPV types associated with? Which strains are low risk and which of these are most prevalent?
- ano-genital condyloma
- low grade cervical dysplasia [CIN 1]
- HPV 6 and 11 = main types of low risk
- also: 40, 42, 43, 44, 54
Which strains are high risk HPV? Which are the most prevalent?
- most prevalent: 16 [55% of cervical cancers] and 18 [15% of cervical cancers]
- less prevalent: 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68
What are high risk HPV types associated with?
- high grade dysplasia
- cervical cancer
- persistent HPV is greatest risk for malignant transformation
What types of cancers [besides cervical] is HPV associated with?
70-80% of anal cancers
40-50% of vulva/vaginal cancers
40-50% of penile cancers
25-60% of oral/oropharyngeal cancers
What is a pap smear?
screening test for cervical cancer –> use exfoliated cervical cells collected transvaginally
How is HPV transmitted?
sexual transmission
What are the classifications of pap smear finding?
- NILM = negative for intra-epithelial lesion malignancy
- ASC = atypical squamous cells
- SIL = squamous intrapeithelial lesion
- LSIL = low grade SIL [mild dypslasia, CIN1]
- HGSIL = high grade SIL [moderate/severe dysplasia, carcinoma in situ [CIS], CIN2/3]
How do you get rid of HPV
most HPV clear spontaneously [including both high and low risk types]
What are co-factors for cervical cancer risk along with HPV infection?
- long term use of oral contraceptive
- high number full-term pregnancies
- tobacco smoking
- past infection with HSV-2 and chlamydia trachomatis
Does having an oncogenic form of HPV mean you will get cancer?
having oncogenic HPV is necessary but not sufficient
Why are HPV 16/18 so causative of cancer?
- they are more likely to give persistent infection rather than clear right away
- shorter latency [shorter time between infection and seeing clinically significant disease]
What are viral properties of HPV?
- non-enveloped
- DNA virus
- double stranded circular genome
- icosahedral capsid
What is structure of HPV genome?
- early E region codes for proteins that control DNA replication
- – viral replication proteins E1, E2, E3, E4
- – oncogenic transforming proteins E6, E7
- late L region codes for major capsid protein L1 and minor capsid protein L2
- non-coding upstream regulatory region
What is importance of E6 and E7 HPV protein?
they are oncogenic transforming proteins
What controls expression of E6 and E7 proteins in HPV?
- E2 viral replication protein represses E6/E7 transcription
- integration of viral genome in host DNA allows E6/E7 to be over expressed
What is function of E6 HPV protein?
- inhibits p53 protein
- —> inhibits apoptosis, promotes loss of cell-cycle control
What is function of E7 HPV protein?
- degrades pRB [retinoblastoma protein, tumor suppressor]
- —> accelerates DNA synthesis, disrupts cell cycle control
Which class of HPV antigens gives humoral immune response?
two classes of HPV antigens: early and late proteins
early: humoral immune response modest or absent
late: get consistent/strong neutralizing antibody response
What are the late protein antigens of HPV?
capsid antigens
How does HPV evade immune system?
- it doesn’t infect APCs
- infected keratinocytes less susceptible than other infected cell to CTL lysis –> little tissue destruction
- virus infects only epithelium without blood-borne phase
- poor immune response to early viral protein
- theres is variable immune response to late viral capsid proteins
How do you classify types of papillomaviruses?
L1 gene –> classified as different type if L1 nucleotide seq is at least 10% dissimilar
What type of vaccine is HPV vaccine?
- type specific sub-unit vaccine
- antigen is virus-like particle [VLP] = virus shells
What strains are in the HPV2 vaccines?
HPV 16, 18
What strains are in the HPV4 vaccines?
HPV 6, 11, 16, 18
