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Microbiology Part 2 > Lec 37 HPV > Flashcards

Lec 37 HPV Flashcards

1
Q

What are low risk HPV types associated with? Which strains are low risk and which of these are most prevalent?

A
  • ano-genital condyloma
  • low grade cervical dysplasia [CIN 1]
  • HPV 6 and 11 = main types of low risk
  • also: 40, 42, 43, 44, 54
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2
Q

Which strains are high risk HPV? Which are the most prevalent?

A
  • 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
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3
Q

What are high risk HPV types associated with?

A
  • high grade dysplasia
  • cervical cancer
  • persistent HPV is greatest risk for malignant transformation
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4
Q

What types of cancers [besides cervical] is HPV associated with?

A

70-80% of anal cancers
40-50% of vulva/vaginal cancers
40-50% of penile cancers
25-60% of oral/oropharyngeal cancers

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5
Q

What is a pap smear?

A

screening test for cervical cancer –> use exfoliated cervical cells collected transvaginally

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6
Q

How is HPV transmitted?

A

sexual transmission

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7
Q

What are the classifications of pap smear finding?

A
  • 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]
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8
Q

How do you get rid of HPV

A

most HPV clear spontaneously [including both high and low risk types]

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9
Q

What are co-factors for cervical cancer risk along with HPV infection?

A
  • long term use of oral contraceptive
  • high number full-term pregnancies
  • tobacco smoking
  • past infection with HSV-2 and chlamydia trachomatis
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10
Q

Does having an oncogenic form of HPV mean you will get cancer?

A

having oncogenic HPV is necessary but not sufficient

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11
Q

Why are HPV 16/18 so causative of cancer?

A
  • they are more likely to give persistent infection rather than clear right away
  • shorter latency [shorter time between infection and seeing clinically significant disease]
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12
Q

What are viral properties of HPV?

A
  • non-enveloped
  • DNA virus
  • double stranded circular genome
  • icosahedral capsid
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13
Q

What is structure of HPV genome?

A
  • 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
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14
Q

What is importance of E6 and E7 HPV protein?

A

they are oncogenic transforming proteins

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15
Q

What controls expression of E6 and E7 proteins in HPV?

A
  • E2 viral replication protein represses E6/E7 transcription

- integration of viral genome in host DNA allows E6/E7 to be over expressed

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16
Q

What is function of E6 HPV protein?

A
  • inhibits p53 protein

- —> inhibits apoptosis, promotes loss of cell-cycle control

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17
Q

What is function of E7 HPV protein?

A
  • degrades pRB [retinoblastoma protein, tumor suppressor]

- —> accelerates DNA synthesis, disrupts cell cycle control

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18
Q

Which class of HPV antigens gives humoral immune response?

A

two classes of HPV antigens: early and late proteins

early: humoral immune response modest or absent
late: get consistent/strong neutralizing antibody response

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19
Q

What are the late protein antigens of HPV?

A

capsid antigens

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20
Q

How does HPV evade immune system?

A
  • 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
21
Q

How do you classify types of papillomaviruses?

A

L1 gene –> classified as different type if L1 nucleotide seq is at least 10% dissimilar

22
Q

What type of vaccine is HPV vaccine?

A
  • type specific sub-unit vaccine

- antigen is virus-like particle [VLP] = virus shells

23
Q

What strains are in the HPV2 vaccines?

A

HPV 16, 18

24
Q

What strains are in the HPV4 vaccines?

A

HPV 6, 11, 16, 18

25
Q

HPV2 vs HPV4: antigen and adjuvant

A

HPV2

  • antigen: baculovirus expression vector system in insect cells
  • adjuvant: alum

HPV4

  • antigen: yeast system
  • adjuvant: ASO4
26
Q

Is HPV2 or HP4 better at producing neutralizing antibodies to HPV16/18?

A

HPV2 is better

27
Q

What is gardasil?

A

HPV4 vaccine

28
Q

What is cervarix?

A

HPV2 vaccine

29
Q

Which HPV vaccine has more potent adjuvant? What does this mean?

A

HPV2 –> might influence duration of immune response and cross-protection against other HPV types not in vaccine

30
Q

What is the next HPV vaccine under investigation?

A

9 valent vaccine

31
Q

What are recommendations for giving HPV2?

A
  • girls age 11 or 12
  • girls/women 13-26 who did not get all 3 doses when they were younger

ideal is to give before onset of sexual activity

32
Q

What are recommendations for HPV4?

A
  • girls and boys 11-12
  • girls 13-26 or guys 13-21 who did not previously get doses
  • through age 26 for msm or immunocompromised men

ideal is to give before onset of sexual activity

33
Q

What are risk factors for anal cancer besides HPV?

A

75-80% of anal cancer related to HPV

other risk factors: number of lifetime sexual partners, receptive anal intercourse, immunosuppression

34
Q

What is the anal T zone?

A
  • transition from stratified squamous to columnar epithelium
  • similar to cervical T zone
  • location where vast majortiy of anal dysplastic lesions occur
35
Q

What are AIN?

A

anal intraepithelial neoplasia = neoplastic precursor that occurs in anal t zone

36
Q

What are risk factors for penile cancer?

A

40-50% linked to RPV

risk factors: lack of circumcision, chronic inflammation

37
Q

What are risk factors for oropharyngeal cancer?

A
  • up to 60% in US associated wtih HPV-16

- other risks: tobacco, alcohol, number of lifetime partners

38
Q

Is there any test available for clinical use to determine whether female has an HPV type?

A

nope!

39
Q

How is HPV transmitted?

A
  • mostly penetrative sexual contact

- some non-penetrative sexual contact

40
Q

What is disease associated with oral HPV?

A

strong association with oropharyngeal cancer

41
Q

If the HPV vaccine 3 dose schedule is interrupted what do you do?

A
  • do not need to restart series
  • if series interrupted after first dose –> administer as soon as possible, separate 2nd and 3rd doses by at least 12 wks
42
Q

Are there any ACIP recommendations for specific groups?

A
  • no recommendation for those with history of dysplasia

- ACIP recommendations address certain special populations

43
Q

If patient had previous cervical dysplasia should you give HPV vaccine?

A

no specific recommendation currently –> discuss with patient and let them make their decision

44
Q

What are current ways of testing HPV?

A
  • serology
  • viral shedding
  • cytology test [do with cervical cancer screening]
45
Q

What are downsides of serology testing for HPV?

A
  • under-estimates number of infected individuals
  • people with current/past infection may not always develop antibodies [<70% of those with HPV will react to antibody test]
46
Q

What are two types of viral shedding test for HPV?

A
  • hybrid capture test: pooling 13 common high-risk types

- type specific test: DNA PCR type specific viral testing of E6/E7 mRNA

47
Q

What is evidence of HPV infection in pap smear?

A

atypical cells of undetermined significance or squamouts in

48
Q

How is HPV persistence currently identified?

A

by viral shedding not serologic testing

Microbiology Part 2 (30 decks)

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