Histopathologic Features

1

Human Papillomavirus in the HIV-infected Patient
Elizabeth A. Stier, MDAssistant
ProfessorDepartment of Obstetrics and
GynecologyBoston Medical Center
2
Cancer rates in the US

• Incidence per 100,000
• total population HIV
  infected
• Cervical cancer 8.9 9-20
• Vulvar cancer 1.2 7.9
• Anal cancer
• Women 1.2 3.9
• Men 0.9 18 -144

Cancer in N America 1994-1998 Frisch, JNCI
2000
3
HPV
Double-stranded DNA virus

• 30-40 anogenital
• 15-20 oncogenic (high risk) types, include
• 16, 18, 31, 33, 35, 39, 45, 51, 52, 58
• Non-oncogenic (low risk) types include
• 6, 11, 40, 42, 43, 44, 54

4
Cancers attributable to oncogenic HPV types, US
(2002)
2002 US cancer stats, CDC/NCI 2005 DM Parkin
2006 Int J Cancer
5
HPV and cancer
Daling, Cancer, 2004 Bosch, JNCIM, 2003
6
Natural History of HPV Infection
01 Year
05 Years
120 Years
Invasive Cervical Cancer
InitialHPV Infection
ContinuingInfection
CIN 2/3
CIN 1
Cleared HPV Infection
Pinto AP, Clin Obstet Gynecol. 2000
7
Prevalence HPV DNA cervix
Palefsky, JNCI, 1999 Jamieson, AmJ ObGyn 2002
8
HPV DNA in HSIL cervix
Clifford GM, AIDS 2006
9
IgG seroprevalence HPV women
Viscidi RP Canc Epi Bio Prev 2005
10
Cervical and anal HPV -- women
Pre-HAART data
Palefsky, J Inf Dis, 2001
11
Anal cancer and cervical cancer are very similar

• Similar histology
• Arise in the transformation zone
• Strongly associated with HPV
• Frequently associated with dysplasia
• May be preceded by squamous intraepithelial
  changes which are also associated with HPV

12
Anal dysplasia in men, based on cytology
(post-HAART)

• Abnormal cytology 44-81
• HSIL 6-25

Palefsky, 2005 Piketty 2003 Wilkin 2004 Mathews
2004 Kreuter 2005
13
Effect of HAART
- Decrease increase no change
14
Anal HPV infection and AIN in the HAART era
(MSM, n357)

• AIN 2-3 52
• HPV 95
• gt6 HPV types 40

Palefsky, AIDS, 2005
15
Anal HPV DNA MSM
Palefsky JID 1998
16
IgG seroprevalence HPV MSM
Hopfl R BMC ID 2003 Hagensee ME JID 1997
17
HPV prophylactic vaccines
HPV VLP

• Recombinant L1 capsid proteins that form virus
  like particles (VLP)
• Non-infectious and non-oncogenic
• Produce high levels of neutralizing antibody

18
HPV prophylactic vaccines

• Quadrivalent HPV 6,11,16,18 vaccine approved by
  the FDA in June 2006
• Bivalent HPV 16, 18 vaccine completing Phase III
  trials
• Both prevent persistent infections and CIN 2,3
  with HPV types in vaccines

19
HPV16 Antibody response
cRIA competitive radioimmunoassay.
Mao C Ob Gyn 2006
20
Phase III quadrivalent vaccine

• HPV 16/18 associated CIN2,3 or AIS
• Vaccine Placebo
• Events Events Efficacy
• 0 41 100
• Genital Warts
• Vaccine Placebo
• Events Events Efficacy
• 1 91 99

Vaccine n7732 Placebo n7710
21
Quadrivalent vaccine studies in HIV patients
should open soon

• Goal to evaluate safety, tolerability and
  immunogenicity in the HIV-infected patient
• Efficacy studies to follow pending results

22
Quadrivalent vaccine studies in HIV patients

• Women
• Joint ACTG/AMC study (PI J Aberg)
• -- stratified by HIV immune status
• Men
• Joint AMC/ACTG study (PI T Wilkin)
• -- stratified by anal HPV DNA status