3. Anal cancer - HIV-NAT
3. Anal cancer - HIV-NAT
3. Anal cancer - HIV-NAT
You also want an ePaper? Increase the reach of your titles
YUMPU automatically turns print PDFs into web optimized ePapers that Google loves.
AIN/anal <strong>cancer</strong><br />
Joel Palefsky, M.D., F.R.C.P.(C)<br />
Professor of Medicine<br />
University of California, San Francisco<br />
<strong>HIV</strong>-<strong>NAT</strong> 2012
Disclosures<br />
• Merck and Co- study investigator,<br />
research grant support, advisory boards
HPV infection and productive life cycle<br />
Virus introduced<br />
through microabrasion<br />
Infectious virions shed<br />
Virion assembly<br />
Viral DNA replication<br />
Late HPV protein<br />
production<br />
L1 & L2<br />
Virus<br />
infection<br />
Early HPV protein<br />
production<br />
E1, E2, E4, E5, E6, & E7<br />
Adapted from Doorbar J. J Clin Virol. 2005;32S:S7–S15.
<strong>Anal</strong> Cancer
Spectrum of HPV Disease<br />
Morphologic Continuum
Age-adjusted incidence rate<br />
(per 100,000)<br />
Age-adjusted incidence rate<br />
of anal <strong>cancer</strong> by gender and year of diagnosis<br />
2<br />
1.8<br />
Female<br />
1.6<br />
1.4<br />
Male<br />
1.2<br />
1<br />
0.8<br />
0.6<br />
0.4<br />
1975 1979 1983 1987 1991 1995 1999 2003 2007<br />
6
<strong>Anal</strong> and cervical <strong>cancer</strong> incidence<br />
• Cervical <strong>cancer</strong> prior to cervical cytology<br />
screening: 40-50/100,000<br />
• Cervical <strong>cancer</strong> currently: 8/100,000<br />
• <strong>Anal</strong> <strong>cancer</strong> among <strong>HIV</strong>- MSM: up to<br />
37/100,000<br />
7
Incidence of HPV-associated <strong>cancer</strong>s in<br />
<strong>HIV</strong>-<strong>cancer</strong> registry match<br />
Frisch et al; JNCI 2000; 92: 1500-10
HPV Infection<br />
<strong>HIV</strong> Infection<br />
HPV<br />
HPV<br />
HPV<br />
Death<br />
N<br />
LSIL<br />
Anogenital Disease<br />
HSIL<br />
Cancer<br />
Immune suppression<br />
Genetic changes
Recent reports of incidence in anal<br />
<strong>cancer</strong> since introduction of HAART<br />
• 75/100,000 person-years among <strong>HIV</strong>+ MSM since 1999 1<br />
• 78/100,000 person-years among <strong>HIV</strong>+ MSM since 2000 2<br />
• 137/100,000 person-years among <strong>HIV</strong>+ MSM since 1996 3<br />
1<br />
Piketty C et al. AIDS. 2008;22:1203-1211.<br />
2<br />
Patel et al. Ann Intern Med. 2008;10(148):728-736<br />
3<br />
D’Souza G et al. J Acquir Immune Defic Syndr. 2008;48(4):491-499.<br />
10
Prevalence, %<br />
Prevalence of anal HPV among MSM<br />
Population-based data<br />
All participants<br />
<strong>HIV</strong>-negative<br />
participants<br />
<strong>HIV</strong>-positive<br />
participants<br />
Chin-Hong et al. Ann Int Med. 2008;149;300-6.<br />
11
Percent<br />
<strong>Anal</strong> and cervical HPV infection in<br />
<strong>HIV</strong>-positive women and <strong>HIV</strong>-negative<br />
women at high risk of <strong>HIV</strong> infection<br />
90<br />
80<br />
70<br />
60<br />
<strong>Anal</strong><br />
Cervical<br />
68<br />
77<br />
56<br />
83<br />
64<br />
50<br />
40<br />
30<br />
20<br />
10<br />
42<br />
27 26<br />
0<br />
<strong>HIV</strong>-<br />
<strong>HIV</strong>+<br />
CD4 >500<br />
<strong>HIV</strong>+<br />
CD4 200-500<br />
<strong>HIV</strong>+<br />
CD4
Case 1<br />
45 year old <strong>HIV</strong>+ woman<br />
• RP has been <strong>HIV</strong>-infected for 10 years<br />
• Nadir CD4 level 150<br />
• Began ART 4 years ago, current CD4= 395, VL<br />
undetectable<br />
• History of CIN 3 treated with cryotherapy 8 years ago<br />
• Vulvar intraepithelial neoplasia 2 treated 3 years ago<br />
• 30 pack-year smoking history, smokes 1 PPD
Case 1<br />
• History of rectal bleeding for 6 months<br />
• Bright red blood with bowel movements<br />
and on toilet tissue<br />
• Dull aching pain chronically, increasing<br />
with bowel movements<br />
• No weight loss, good appetite
Case 1 question 1-<br />
What is the differential diagnosis?<br />
• 1. <strong>Anal</strong> warts<br />
• 2. High-grade anal intraepithelial neoplasia<br />
• <strong>3.</strong> <strong>Anal</strong> <strong>cancer</strong><br />
• 4. Internal hemorrhoids<br />
• 5. External hemorrhoids
Case 1 question 1-<br />
What is the differential diagnosis?<br />
• 1. <strong>Anal</strong> warts<br />
• 2. High-grade anal intraepithelial neoplasia<br />
• <strong>3.</strong> <strong>Anal</strong> <strong>cancer</strong><br />
• 4. Internal hemorrhoids<br />
• 5. External hemorrhoids
Why?<br />
• Bleeding per rectum<br />
• PAIN!!<br />
• History of CIN and VIN<br />
• Smoker
Case 1 question 2<br />
What is the appropriate work-up?<br />
• 1. Abdominal CT scan<br />
• 2. Digital anorectal exam<br />
• <strong>3.</strong> High resolution anoscopy<br />
• 4. <strong>Anal</strong> HPV test<br />
• 5. Answers 2 and 3
Case 1 question 2<br />
What is the appropriate work-up?<br />
• 1. Abdominal CT scan<br />
• 2. Digital anorectal exam<br />
• <strong>3.</strong> High resolution anoscopy<br />
• 4. <strong>Anal</strong> HPV test<br />
• 5. Answers 2 and 3
Progression of HGAIN to <strong>Anal</strong> Cancer<br />
Case 1
Superficially Invasive SCCA<br />
Detected by HRA
Take home messages<br />
• High index of suspicion in at-risk groups<br />
• Pain is an important symptom<br />
• Need to FEEL and SEE<br />
• <strong>Anal</strong> <strong>cancer</strong> can occur at all CD4 levels<br />
and with good <strong>HIV</strong> control
Case 2<br />
35 year old <strong>HIV</strong>+ MSM<br />
• <strong>HIV</strong>-infected for 7 years<br />
• Nadir CD4 level 110, on ART for 6 years, <strong>HIV</strong><br />
VL non-detectable<br />
• Current CD4 level 580<br />
• History of receptive anal intercourse with 30<br />
partners, has one regular partner currently<br />
• History of anal warts 20 years ago, treated<br />
with liquid nitrogen, not checked since
Case 2<br />
35 year old <strong>HIV</strong>+ MSM<br />
• Denies bleeding per rectum<br />
• No pain<br />
• Not aware of any anal wart recurrence<br />
• Weight stable, good appetite<br />
• Non-smoker, no recreational drugs
Case 2 question 1<br />
What is the appropriate work-up?<br />
• 1. <strong>Anal</strong> cytology<br />
• 2. Digital anorectal exam<br />
• <strong>3.</strong> High resolution anoscopy<br />
• 4. <strong>Anal</strong> HPV test<br />
• 5. Answers 1, 2 and <strong>3.</strong>
Case 2 question 1<br />
What is the appropriate work-up?<br />
• 1. <strong>Anal</strong> cytology<br />
• 2. Digital anorectal exam<br />
• <strong>3.</strong> High resolution anoscopy<br />
• 4. <strong>Anal</strong> HPV test<br />
• 5. Answers 1, 2 and <strong>3.</strong>
AIN 3
Case 2-question 2<br />
What is the best treatment approach?<br />
• 1. Follow-up without treatment<br />
• 2. Infra-red coagulation<br />
• <strong>3.</strong> 85% trichloracetic acid<br />
• 4. Therapeutic HPV vaccination<br />
• 5. Liquid nitrogen
Case 2-question 2<br />
What is the best treatment approach?<br />
• 1. Follow-up without treatment<br />
• 2. Infra-red coagulation<br />
• <strong>3.</strong> 85% trichloracetic acid<br />
• 4. Therapeutic HPV vaccination<br />
• 5. Liquid nitrogen
Treatment with infrared coagulation<br />
• Well tolerated with substantially less pain compared<br />
with surgical treatment, minor bleeding for a few<br />
days to weeks, very low incidence of significant<br />
problems<br />
IRC 2100 TM Infrared Coagulator<br />
Redfield Corporation<br />
Rochelle Park, NJ
Take home messages<br />
• Very high rate of high-grade AIN in <strong>HIV</strong>infected<br />
MSM= high index of suspicion<br />
• HGAIN can occur at all CD4 levels and<br />
with good <strong>HIV</strong> control<br />
• <strong>Anal</strong> cytology mostly useful for high<br />
positive predictive value of HSIL<br />
• HPV test of limited value<br />
• Need to rule out <strong>cancer</strong>
Conclusions<br />
• Better survival on ART = increased risk of HPVassociated<br />
<strong>cancer</strong>?<br />
• Risk for anal <strong>cancer</strong> will likely increase in<br />
absence of screening and treatment of AIN
What can we do now?<br />
• Collect data!<br />
• Optimize screening regimens<br />
• Optimize treatment for HGAIN<br />
• Digital anorectal exam<br />
• ? Begin screening for AIN/anal <strong>cancer</strong> in <strong>HIV</strong>+<br />
men and women<br />
• Prevent HPV infection through vaccination
<strong>Anal</strong> cytology screening for AIN<br />
Screen<br />
Normal ASCUS LSIL HSIL<br />
Repeat in 12 months (<strong>HIV</strong>+)<br />
Repeat in 2-3 years (<strong>HIV</strong>−)<br />
Anoscopy with biopsy<br />
No lesion seen<br />
AIN 1 AIN 2/3<br />
Treat or follow<br />
Treat<br />
Chin-Hong PV et al. J Infect Dis. 2004;90:2070-2076.<br />
35
Related Cases<br />
Quadrivalent HPV vaccine in males: efficacy against<br />
HPV 6/11/16/18-related AIN and anal <strong>cancer</strong> in MSM 1<br />
Per-Protocol Efficacy Population<br />
50<br />
GARDASIL<br />
40<br />
30<br />
20<br />
10<br />
77.5%<br />
Reduction<br />
(40, 93)<br />
5<br />
24<br />
Placebo<br />
0<br />
n=194 n=208<br />
HPV 6-, 11-, 16-, or 18-Related<br />
AIN and <strong>Anal</strong> Cancer<br />
1<br />
Palefsky J, Giuliano et al. NEJM 2011;365:1576-85.<br />
36
What can we do now?<br />
• Vaccinate girls against HPV prior to<br />
initiation of sexual activity!<br />
• Vaccinate boys against HPV?<br />
• Protect against anal HPV infection/<strong>cancer</strong><br />
• Reduce risk of spread to women?<br />
• Reduce risk of other HPV-related<br />
<strong>cancer</strong>s, including oral <strong>cancer</strong>?<br />
• Reduce risk of acquiring <strong>HIV</strong> infection?
ขอขอบคุณส ำหรับควำมสนใจชนิดของ!
Change language