HUMAN PAPILLOMAVIRUS (HPV)

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SCABIES, LICE AND HPV
Michael E. Hagensee, M.D. Ph.D. Associate
Professor Department of Medicine Section of
Infectious Disease LSUHSC
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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.

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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

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SCABIES
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SCABIES
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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
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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  
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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
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HUMAN PAPILLOMAVIRUS (HPV)

• Papovavirus
• Most common viral STD
• ds DNA virus of 7.9 kB
• Entire DNA sequence is
• known

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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

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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
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GENITAL WARTS
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GENITAL WARTS
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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

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GENITAL WARTS
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GENITAL WARTS
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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

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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

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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

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CERVICAL CANCER
CIN II
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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
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CERVIX - ANATOMY
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CERVIX - ANATOMY
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CERVIX - ANATOMY
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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
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HPV DIAGNOSIS PAP SMEAR
Normal, ASCUS Atypical Squamous Cells of
Unclear Significance
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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
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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

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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
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SCREENING METHODS
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CERVICAL CANCER SCREENING METHODS
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HIGH-RISK HPV INFECTION TREATMENT

• OBSERVATION
• CRYOTHERAPY-LASER
• CONE BIOPSY-SURGERY
• RETINOIDS??

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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
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HPV VLPs
HPV capsids EM and 3-D Reconstruction
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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
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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.
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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.
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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.