PPT

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Slide 1 of 23
Say Yes to the Test!
Jeffrey L. Lennox, MD
Professor of Medicine
Emory University School of Medicine
Atlanta, GA
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA. IAS–USA
Slide 2 of 23
A Brief History of the
Cervical Pap Smear
• 1928 – Papanicolaou presents methods and
case reports. Received press attention, but
little interest from medical establishment.
• 1941 – Papanicolaou publishes additional data.
• 1955 – First large study completed.
• Late 50’s–60’s – Refinements, training of
cytologists.
• 1984 – 82% reduction in cervical cancer
mortality compared to 1940’s.
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 3 of 23
In the 30 years after the
description of the Pap smear, but
before its acceptance, cervical
cancer was the #1 cause of
cancer mortality in women
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 4 of 23
Why Did the Medical Establishment
Reject Cervical Pap Smears?
• New test, no proof of efficacy and benefit
• Insufficient training and expertise of
pathologists
• Additional costs to screen
• Wide variability in results between labs
• Bias against women, particularly with
regards to STIs
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 5 of 23
Anal Pap Smear Among HIV-Infected
Men: 27 years since first description
• 1986 – “Association Between Anorectal
Dysplasia, HPV and HIV in Homosexual Men”*
• Obtained rectal Paps from 61 men, 39 reexamined 6-12 months later
• 31% HIV+
• Findings:
−24/61(39%) had dysplasia
−Dysplasia associations – history of anal warts,
frequent receptive anal sex, HIV+
−Persistent dysplasia more common in HIV+
* Frazer IH, Lancet 1986, 328(8508):657–660
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 6 of 23
Incidence of Anal Cancer in HIV-Infected
Persons During HAART Era
34,189 HIV-infected patients from 13 North American cohorts
131-159 per 100,000 person-years, 31-59%
higher than the peak for cervical cancer!
Silverberg MJ, Clin Inf Dis 2012, 54(7):1023-34
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 7 of 23
Are all HIV-infected men equally at risk?
• Cross sectional study of 200 MSM and 123 MSW,
all HIV-infected, who had anoscopy performed.1
• Dysplasia present: 21% MSM, 7% MSW
Anal Dysplasia
Characteristic
OR (95%CI)
p
CD4 <200
1.7 (0.8-4.4)
0.235
History rectal condyloma
2.8 (1.4-5.8)
0.004
Receptive anal intercourse
4.3 (2.2-8.4) <0.001
• Military cohort- median anal cancer age 42 years.2
• Persons with HIV >15 years had 12x higher rate
than those <5 years (p<0.01)
1. Abramowitz L, AIDS 2007, 21(11): 1457-65. 2. Crum-Cianflone and Marconi, AIDS, Feb 2010
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 8 of 23
How Well does the Anal Pap do When
Compared to Biopsy?
Chiao EY,JAIDS 2006;43:223-233
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 9 of 23
Cost Effectiveness of Anal Cytology
Screening in MSM
Population
Frequency
HIV+ MSM
HIV- MSM
Annually
Q 3 years
Cost per
QALY Saved
$16,000
$7,800
Goldie SJ. JAMA 1999, 281(19):1822-1829
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 10 of 23
Cost Effectiveness of Other Common
Interventions
Intervention
Q2 yr cervical Pap age 30-39
PCP prophylaxis
Cost/yr life
$2,300
$16,000
HTN screening men age 40
Treat diastolic BP 95-104, age 40
Statin for men age 40, TC >300
$23,000
$32,000
$23,000
Colonoscopy for CA screening
Cervical Pap, HPV vaccinated woman
$90,000
$110,000
Anal
Pap
Goldie SJ. JNCI 2004;96:604-615
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 11 of 23
Cost Effectiveness of HRA Only vs.
Pap for Screening - Methods
• 401 HIV+ MSM had HRA, Pap, and HPV
digene assay done at same visit.
• 98/401 (24%) had AIN 2/3 based on biopsy
during HRA.
• For sensitivity and specificity the HRA biopsy
was assumed to be gold standard.
Test
Sensitivity
Specificity
Cost/Test
HRA
-
-
$193
Pap
84
39
$90
Ocogenic HPV
100
16
$95
Lam JMC, AIDS 2011, 25: 635-42
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Cost Effectiveness of
HRA Only vs. Pap - Results
Slide 12 of 23
Insert figure
HPV+ : HRA
Pap > ASCUS: HRA
HRA
Conclusion: Direct HRA is the most cost effective
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 13 of 23
Random Biopsy Increases HGSIL
Diagnostic Rate of HRA
• 372 patients had HRA with directed and
random biopsies done at same visit
• 124 patients with HSIL, 11 (9%) diagnosed
by random biopsy
Silvera R, CROI 2013, #142
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 14 of 23
New York State Guidelines
Clinicians should obtain anal cytology
at baseline and annually in the
following HIV-infected populations:
* Men who have sex with men
* Any patient with a history of anogenital
condylomas
* Women with abnormal cervical and/or
vulvar histology
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 15 of 23
My Conclusions –
1. For those with HIV of >5 years
duration, use direct HRA if available
for MSM and other high risk people
2. Use Pap as second choice, followed
by HRA
3. When performing HRA do 1-3
random biopsies
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 16 of 23
Anal Cancer Prevention
st
1 !
Kimberly A. Workowski, MD
Professor of Medicine
Emory University School of Medicine
Atlanta, GA
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA. IAS–USA
Slide 17 of 23
Natural History of HPV Infection
• HPV persistence is a prerequisite for
abnormal anogenital cytology
• Most infections self limited
– Limited data on persistence in specific anatomic
sites (HIV+)
– Anal dysplasia +/- treatment not well defined
• Incidence and clearance rates can differ
among HPV types
– HPV16 lower anal clearance rate (dePokomany 2009)
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 18 of 23
HPV Vaccine Efficacy
Outcome
Sex
Vaccine
Randomized Vaccine
Controlled
Trials
Efficacy
Cervical precancer
Bivalent and
Quadrivalent
F
>92%
Vaginal/Vulvar
precancer
Quadrivalent
F
100%
Anal precancer
Quadrivalent
M
75%
Genital warts
Quadrivalent
F, M
>89%
No evidence of efficacy against existing HPV infection or disease
Paavonen J et al. Lancet 2009;374:301-14, Kjaer S et al. Cancer Prev Res 2009;2:868-78, Hildesheim A et al. JAMA 2007;298:743-53,
Future I/II Study Group, BMJ 2010;341, The Furture II Study Group Lancet 2007;369:1861-8, Palefsky J et al. NEJM 2011;365:1576-85
Gardasil Package Insert, page 504 Table 12
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 19 of 23
HPV vaccine–preventable fractions of various
anal disease categories among HIV+ MSM
Sahasrabuddhe. J Infect Dis. 2013 Feb;207(3):392-401.
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 20 of 23
Time to recurrence of high-grade anal neoplasia among vaccinated
and unvaccinated oncogenic human papillomavirus–infected men
who have sex with men with a history of high-grade anal neoplasia
New York City, April 2007–
April 2011 (n = 105).
Figure 2. Swedish KA, Factor SH,
Goldstone SE. Prevention of recurrent
high-grade anal neoplasia with
quadrivalent human papillomavirus
vaccination of men who have sex with
men: a nonconcurrent cohort study. Clin
Infect Dis. 2012 Apr; 54(7):891-8.
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 21 of 23
Predictors of progression from low-grade
AIN (LGAIN) to high-grade AIN (HGAIN)
Coutlée F.Sex Health. 2012 Dec;9(6):547-55.
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 22 of 23
Logistic Regression Analysis of Factors Associated
with Prevalent Abnormal Anal Cytology among MSM in
the SUN Study, 2004–2006
Conley L. J Infect Dis. 2010 Nov 15;202(10):1567-76.
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.
Slide 23 of 23
Screening for Anal Dysplasia and
Cancer in MSM
 CDC, HIVMA OI guidelines:
consider anal Pap tests in MSM
– Evidence is limited
•
•
•
•
Natural history
Reliability of screening methods
Safety and response to treatments
Programmatic support needed
– Patients with abnormal results
should be evaluated with highresolution anoscopy (HRA)
 HPV DNA screening of rectum
not recommended
From JL Lennox, MD, and KA Workowski, MD, at Atlanta, GA: April 10, 2013, IAS-USA.

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