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HUMAN PAPILLOMAVIRUS (HPV)

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Title: HUMAN PAPILLOMAVIRUS (HPV)


1
SCABIES, LICE AND HPV
Michael E. Hagensee, M.D. Ph.D. Associate
Professor Department of Medicine Section of
Infectious Disease LSUHSC
2
DISCLOSURE
  • I have no financial interests or other
    relationship with manufacturers of commercial
    products, suppliers of commercial services, or
    commercial supporters. My presentation will not
    include any discussion of the unlabeled use of a
    product or a product under investigational use.

3
STDs AND OTHER GYNECOLOGIC INFECTIONS
  • Objectives
  • To be able to diagnose and treat scabies
  • To be able to diagnose and treat pubic lice
  • To know about the disease that HPV cause and
  • how to treat/prevent them

4
SCABIES
5
SCABIES
6
SCABIES
A. Etiology Sarcoptes scabiei-human itch
mite   B. Epidemiology 1. More than 100
million cases per year 2. Itching due to
excretions from burrowing mites 3. Increase
spread by close contact, crowding 4. Medical
practitioners are at high risk   C. Clinical
manifestations 1. Itching increases at
night and after a hot shower 2. Burrows-dark
wavy lines ending in small bleb 3. Usual sites
wrists, fingers, elbows and on penis 4. Usually
15 mites per person
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SCABIES
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SCABIES
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SCABIES
5. Norwegian scabies (crusted) - thousands to
millions of mites per person - seen only in
immunosuppressed (HIV) individuals - erythema,
thick keratotic crusts and dystrophic nails   D.
Diagnosis Find mite of eggs in scraping vs
empiric   E. Treatment 1. 5 permethrin
cream 2. 1 lindane (not in pregnant women)
3. Anti-pruritics as needed
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LICE
19
LICE
A. Etiology 1. Pediculus humanus var.
capitis - head lice 2. P. humanus var. corporis
- clothing 3. Pthirus pubic - pubic hair   B.
Epidemiology 1. Lice feed on human blood
once a day 2. Saliva of lice produce an
irritating rash 3. Transmitted by close
contact, shared combs, clothing  
20
LICE
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LICE
  C. Clinical manifestations 1. Intensely
pruritic lesions 2. 2-3 mm blue macules
(maculae cerulae) at bite sites   D. Diagnosis
Find nits or adult lice in hair or clothing   E.
Treatment 1. 1 permethrin 2. 0.5
malathion 3. 1 lindane - more toxic and must
apply a second dose 1 week later - does not
kill nits - not in pregnant women 4. Comb out
nits after treatment
26
HUMAN PAPILLOMAVIRUS (HPV)
  • Papovavirus
  • Most common viral STD
  • ds DNA virus of 7.9 kB
  • Entire DNA sequence is
  • known

27
HPV TYPES
Defined by 10 difference in DNA sequence (L1
gene)
  • 1,2 - plantar and
  • common warts
  • 6,11 - condylomata and
  • laryngeal warts
  • 16,18, and others -
  • anogenital malignancies

28
METHODS TO DETECT HPV INFECTION
Clinical diagnosis Genital warts Epithelial
defects See cellular changes caused by the
virus Pap smear screening Directly detect the
virus DNA hybridization or PCR Detect
previous infection (Research Only) Detection
of antibody against HPV Done in the Hagensee
Laboratory
29
GENITAL WARTS
30
GENITAL WARTS
31
HPV EPIDEMIOLOGY GENITAL WARTS
  • Usually caused by HPV 6 or 11
  • Prevalence has increased 2-10x over past 30
    years
  • Most often found on penile shaft and anus in
    men,
  • vulva in women
  • Spontaneous regression seen in 20 of cases

32
GENITAL WARTS
33
GENITAL WARTS
34
GENITAL HPV INFECTION DIFFERENTIAL DIAGNOSIS
  • CONDYLOMA LATUM-SYPHILIS
  • MOLLUSCUM CONTAGIOSUM
  • FIBROEPITHELIOMA AND OTHER CANCERS
  • LICHEN PLANUS
  • OTHER-HSV, LGV, CHANCROID,
  • GRANULOMA INGUINALE

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GENITAL HPV INFECTION TREATMENT
  • OBSERVATION -20 spontaneous regression
  • CRYOTHERAPY -70 cure rate
  • PODOPHYLLIN/ TCA -30 cure rate
  • SURGERY -laser-85 cure rate
  • INTERFERON ALPHA -intralesional and systemic
  • IMIQUIMOD -induces local interferon alpha
    production
  • CIMETIDINE (Tagamet) non-specific immune
    booster

38
HPV EPIDEMIOLOGY ANOGENITAL MALIGNANCY
  • Caused by high risk HPVs-16, 18, 31 and others
  • Occurs mainly in older women-average age 54
    years
  • Associated with increased number of sexual
    partners,
  • smoking, and immune suppression

39
HPV IS ASSOCIATED WITH ANOGENITAL MALIGNANCIES
  • HPV DNA is found in 50-98 of tumors depending
  • on location
  • Oncogenic genes (E6 and E7) of high-risk types
    are
  • expressed in tumors
  • E6 and E7 of high-risk types are oncogenic
    in-vitro
  • Support from many epidemiologic studies

40
CERVICAL CANCER
CIN II
41
CERVICAL CANCER
2nd most common malignancy of women
worldwide More than 500,000 cases per year of
cases declining in USA Over 13,000 cases in US
in 1998 Over 35 mortality
42
CERVIX - ANATOMY
43
CERVIX - ANATOMY
44
CERVIX - ANATOMY
45
COLLECTION OF A PAP SMEAR
CONVENTIONAL
NOW MOST CLINICS HAVE MOVED TO LIQUID-PAP
SMEARS (Thin Prep, SurePath) - preserve the
morphology of the cells better
46
HPV DIAGNOSIS PAP SMEAR
Normal, ASCUS Atypical Squamous Cells of
Unclear Significance
47
HPV PAP SMEARS
Pap smear Normal ASCUS atypical cells
of unclear significance repeat Pap vs
test for HPV DNA LGSIL low grade squamous
intra-epithelial lesion colposcopy with
biopsy HGSIL high grade squamous
intra-epithelial lesion colposcopy with
biopsy and treat Cervical biopsy CIN I
mild dysplasia usually spontaneously regresses
CIN II moderate dysplasia - treat CIN III
severe dysplasia treat Carcinoma in-situ
treat Invasive cervical cancer treat
48
CERVICAL CANCER SCREENING METHODS
  • HPV DNA Testing for questionable cases
  • Normal PAP smear - usual follow up
  • ASCUS - may be cost-effective
  • LGSIL - most regress
  • HGSIL - refer for colposcopy and biopsy

49
CERVICAL CANCER SCREENING METHODS
REFLEX TESTING USING HYBRID CAPTURE II Collect a
cervical swab for DNA testing from all women and
store them Only those women with ASCUS (or
LGSIL) the swab is sent for HPV DNA
testing HCII positive for high-risk HPV then
refer to colposcopy negative for high-risk HPV
then routine yearly screening
50
SCREENING METHODS
51
CERVICAL CANCER SCREENING METHODS
52
HIGH-RISK HPV INFECTION TREATMENT
  • OBSERVATION
  • CRYOTHERAPY-LASER
  • CONE BIOPSY-SURGERY
  • RETINOIDS??

53
PROPHYLACTIC VACCINES AGAINST HPV
Utilizing in-vitro capsid production (VLPs
Virus-Like Particles) Co-discovered by Zhou et
al, Virology 185251, 1991 Kirnbauer
et al, PNAS 8912180, 1992 Hagensee et al, J.
Virology 67315, 1993 Particles made in the
laboratory identical to in-vivo down to a
resolution of 5 microns No infectious
potential Can be made in vaccinia virus,
baculovirus, yeast and bacterial expression
systems
54
HPV VLPs
HPV capsids EM and 3-D Reconstruction
55
PROPHYLACTIC VACCINES AGAINST HPV
COMPANY HPV TYPE PHASE RESULTS
MERCK 6,11,16,18 Approved Gardasil Serologic response Safe
MEDIMMUNE GSK 16, 18 III Serologic response Safe
56
ACIP Recommendations
  • Routine vaccination with 3 doses of quadrivalent
    HPV vaccine for females 1112 years of age
  • Can be started in females as young as 9 years of
    age
  • Catch-up vaccination for females 1326 years of
    age not previously vaccinated or who have not
    completed the full vaccine series
  • Ideally, vaccine should be administered before
    potential exposure to HPV.
  • Each dose of quadrivalent HPV vaccine is 0.5 mL,
    administered intramuscularly.
  • Quadrivalent HPV vaccine is administered in a
    3-dose schedule.
  • The second and third doses should be administered
    2 and 6 months after the first dose.
  • Quadrivalent HPV vaccine can be administered at
    the same visit at which other age-appropriate
    vaccines are provided, such as Tdap, Td, and
    MCV4.

NOTE Per the Prescribing Information,
co-administration of GARDASIL with these vaccines
has not been studied.
Advisory Committee on Immunization Practices
(ACIP). ACIP recommendations for the use of
quadrivalent HPV vaccine. Available at
http//www.cdc.gov/nip/recs/provisional_recs/hpv.p
df. Accessed December 19, 2006.
57
ACIP Recommendations (cont.)
  • Current recommendations for cervical cancer
    screening have not changed for females who
    receive quadrivalent HPV vaccine.
  • Females who have an equivocal or abnormal Pap
    test, a positive Hybrid Capture II high-risk
    test, or genital warts can receive the
    quadrivalent HPV vaccine.
  • Recipients should be advised that the vaccine
    will not have therapeutic effect on existing Pap
    test abnormalities, HPV infection, or genital
    warts. Vaccination would provide protection
    against infection with vaccine HPV types not
    already acquired.
  • Lactating women can receive quadrivalent HPV
    vaccine.
  • Immunocompromised females can receive
    quadrivalent HPV vaccine.
  • However, the immune response to vaccination and
    vaccine effectiveness might be less than in
    females who are immunocompetent.
  • Quadrivalent HPV vaccine is contraindicated in
    people with a history of immediate
    hypersensitivity to yeast or to any vaccine
    component.

ACIP. Recommendations for the use of quadrivalent
HPV vaccine. Available at http//www.cdc.gov/nip/
recs/provisional_recs/hpv.pdf. Accessed December
19, 2006.
58
ACIP Recommendations (cont.)
  • Quadrivalent HPV vaccine is not recommended for
    use in pregnancy.
  • Individuals should report any exposure to the
    vaccine during pregnancy to the vaccine pregnancy
    registry.
  • Quadrivalent HPV vaccine can be administered to
    females with minor acute illnesses.
  • Vaccination of people with moderate or severe
    acute illnesses should be deferred until after
    the illness improves.

ACIP. Recommendations for the use of quadrivalent
HPV vaccine. Available at http//www.cdc.gov/nip/
recs/provisional_recs/hpv.pdf. Accessed December
19, 2006.
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