Download HUMAN PAPILLOMAVIRUS (HPV)

SCABIES, LICE AND HPV
Michael E. Hagensee, M.D. Ph.D.
Associate Professor
Department of Medicine
Section of Infectious Disease
LSUHSC
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.
STDs AND OTHER
GYNECOLOGIC INFECTIONS
Objectives:
1. To be able to diagnose and treat scabies
2. To be able to diagnose and treat pubic lice
3. To know about the disease that HPV cause and
how to treat/prevent them
SCABIES
SCABIES
SCABIES
A. Etiology: Sarcoptes scabiei-human itch mite
B. Epidemiology:
1.
2.
3.
4.
More than 100 million cases per year
Itching due to excretions from burrowing mites
Increase spread by close contact, crowding
Medical practitioners are at high risk
C. Clinical manifestations:
1.
2.
3.
4.
Itching increases at night and after a hot shower
Burrows-dark wavy lines ending in small bleb
Usual sites wrists, fingers, elbows and on penis
Usually 15 mites per person
SCABIES
SCABIES
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
LICE
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
LICE
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
HUMAN PAPILLOMAVIRUS (HPV)
• Papovavirus
• Most common viral STD
• ds DNA virus of 7.9 kB
• Entire DNA sequence is
known
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
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
GENITAL WARTS
GENITAL WARTS
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
GENITAL WARTS
GENITAL WARTS
GENITAL HPV INFECTION
DIFFERENTIAL DIAGNOSIS
• CONDYLOMA LATUM-SYPHILIS
• MOLLUSCUM CONTAGIOSUM
• FIBROEPITHELIOMA AND OTHER CANCERS
• LICHEN PLANUS
• OTHER-HSV, LGV, CHANCROID,
GRANULOMA INGUINALE
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
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
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
CERVICAL CANCER
CIN II
CERVICAL CANCER
2nd most common malignancy of women worldwide
# of cases declining
in USA
Over 13,000
cases in US in 1998
Over 35% mortality
Incidence per 100,000
More than 500,000 cases per year
20
18
15.9
15
17.8
16.3
12.3
9.4
10
5
0
19831987
19901994
Year
19972000
USA
LA
CERVIX - ANATOMY
CERVIX - ANATOMY
CERVIX - ANATOMY
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
HPV DIAGNOSIS – PAP SMEAR
Normal, ASCUS – Atypical Squamous Cells of Unclear Significance
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
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
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
SCREENING METHODS
CERVICAL CANCER
SCREENING METHODS
HIGH-RISK HPV INFECTION
TREATMENT
• OBSERVATION
• CRYOTHERAPY-LASER
• CONE BIOPSY-SURGERY
• RETINOIDS??
PROPHYLACTIC VACCINES
AGAINST HPV
Utilizing in-vitro capsid production:
(VLPs – Virus-Like Particles)
Co-discovered by: Zhou et al,
Virology 185:251, 1991
Kirnbauer et al, PNAS 89:12180, 1992
Hagensee et al, J. Virology 67:315, 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
HPV VLPs
HPV capsids – EM and 3-D Reconstruction
PROPHYLACTIC VACCINES
AGAINST HPV
COMPANY
MERCK
MEDIMMUNE
GSK
HPV TYPE
PHASE
RESULTS
6,11,16,18
Approved
Gardasil
Serologic response
Safe
16, 18
III
Serologic response
Safe
ACIP Recommendations





Routine vaccination with 3 doses of quadrivalent HPV vaccine for
females 11–12 years of age
– Can be started in females as young as 9 years of age
Catch-up vaccination for females 13–26 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.pdf. Accessed December 19, 2006.
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.
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.