Transcript Powerpoint

Catching up on HPV-related cancers:
diagnostic advances and treatment
controversies
Nittaya Phanuphak, MD, PhD
Thai Red Cross AIDS Research Centre
Bangkok, Thailand
Outline
• HPV – HIV – Cancers
• Screening programs to prevent cervical cancer
and anal cancer
• Facts and challenges when making decision to
screen/treat anal pre-cancerous lesions
HPV – HIV – Cancers
• HAART prolongs survival of PLHIV but may have
incomplete immune recovery
• Lack of decline or increased incidence of HPV-related
cancers among PLHIV in the HAART era
Palefsky JM 2011
Cervical cancer in HIV+ women
SIR 8.9 for in situ cancer, 5.6 for invasive cancer
Incidence per 100,000 PY
500
448.9
400
300
200
100
177.3
70.9
In situ
Invasive
89
90.4
0
1980-1989
1990-1995
1996-2004
Chaturvedi AK, et al. J Natl Cancer Inst 2009;101:1120-30.
Anal cancer in HIV+ men and women
Incidence per 100,000 PY
SIR
Males
- MSM
Women
100
In situ
68.6
89.7
33.0
Invasive
34.6
51.8
14.5
100
MEN
80
80
60
60
40
20.7
20
0
10.5
42.3
40
29.5
20
18.3
1.7
1980-1989 1990-1995 1996-2004
Invasive 0
In situ
WOMEN
0
5.2
11.2
5.2
0
1.7
1980-1989 1990-1995 1996-2004
Chaturvedi AK, et al. J Natl Cancer Inst 2009;101:1120-30.
Oropharyngeal cancer in
HIV+ men and women
Incidence per 100,000 PY
50
40
SIR 1.6
30
Invasive
20
10
0
6.5
3.9
0
1980-1989 1990-1995 1996-2004
Chaturvedi AK, et al. J Natl Cancer Inst 2009;101:1120-30.
HPV infection and dysplastic transformation
Normal
Low-grade
squamous
intraepithelial
lesion (LSIL)
High-grade
squamous
intraepithelial
lesion (HSIL)
Cancer
Modified from Palefsky JM 2011
Screening program and
prevention of cervical cancer
• Rates of cervical cancer have declined in
settings where screening programs have been
implemented successfully
– No RCT performed prior to widespread screening
program
– Observational studies confirmed risk of invasive
cancer in women with high-grade cervical
dysplasia
• Screening programs remain difficult to
implement in low and middle-income settings
McCredie MR, et al. Lancet Oncol 2008; 9: 425–34.
McIndoe WA, et al. Obstet Gynecol 1984;64:451-8.
Screening program and
prevention of anal cancer
YES
NO
• More clinics now offer
screening for anal HSIL
among patients at “high
risk” for anal cancer, as
a strategy to prevent
anal cancer, based on
the etiological and
pathological similarities
to cervical cancer
• More research is
needed to understand
the natural history of
anal HSIL and to prove
the efficacy and
acceptability of its
treatment
Pria AD, et al. AIDS 2013; 27: 1185-6.
Grulich AE, et al. Sex Health 2012;9:628-31.
Cervical HPV and histologic HSIL
among HIV+ women
Prevalence (%)
100
80
SUN (US)
THAILAND
100
83
Any HPV types
80
70
High-risk HPV types
60
All histologic SIL
40
16
20
Histologic HSIL
6
0
60
40
35
24
20
19
4
0
HPV
infection
HPV
infection
Histologic
CIN SIL
HPV
infection
HPV
infection
Cervical cancer rate in HIV+ women = 90 / 100,000
Histologic
CIN SIL
• Progression of CIN 3 to cervical cancer = 1 in 80 per year
Kojic EM, et al. Sex Transm Dis 2011;38:253-9.
Ramautarsing R, et al. 27th Int HPV Conf 2011, Berlin, P-32.33.
Chaturvedi AK, et al. J Natl Cancer Inst 2009;101:1120-30.
McCredie MR, et al. Lancet Oncol 2008;9:425-34.
Anal HPV and histologic HSIL
among HIV+ women
Prevalence (%)
100
SUN (US)
90 85
100
THAILAND
Any HPV types
80
80
High-risk HPV types
60
All histologic SIL
40
16
20
9
0
Histologic HSIL
60
40
20
14 9
0
HPV
infection
HPV
infection
Histologic
AIN SIL
HPV
infection
HPV
infection
Anal cancer rate in HIV+ women = 11 / 100,000
AIN
• Anal SIL is as common as cervical SIL
• More common in women with cervical, vulvar, vaginal
high-grade diseases
Hessol NA, et al. AIDS 2009;23:59-70.
Chaithongwongwatthana S, et al. IGCS 2012.
Chaturvedi AK, et al. J Natl Cancer Inst 2009;101:1120-30.
Anal HPV and histologic HSIL
among HIV+ and HIV- MSM
Prevalence
(%)(%)
Prevalence
100
80
60
40
93
82
Meta-analysis
CHINA
Any HPV types
74
61
64
58
29
40
37
22
100
High-risk HPV types
Any HPV types
Histologic HSIL
High-risk HPV types
80
Histologic HSIL
60
20
0
0
HIV-negative
85
59
58
37
40
20
HIV-positive
THAILAND
19
HIV-positive
11
HIV-negative
Anal cancer rate in HIV+ MSM = 78 / 100,000 and in HIV- MSM = 5 / 100,000
• Progression rate of anal HSIL to cancer (per year)
– Theoretical: HIV+ MSM = 1 in 600, HIV- MSM = 1 in 4000
– Australia (73% HIV+ MSM): 1 in 80
Phanuphak N, et al. JAIDS 2013 (In press). Phanuphak N, et al. AIDS 2013 (In press).
Hu Y, et al. JAIDS 2013 (In press). Tong WWY, et al. AIDS 2013 (In press).
Machalek DA, et al. Lancet Oncol. May 2012;13(5):487-500.
Anal HSIL screening
• No standard screening guidelines
• New York State Department of Health AIDS Institute
• Screen at baseline and annually for HIV+: MSM, anogenital
warts, abnormal vulvar/cervical histology
New York State Department of Health AIDS Institute: www.hivguidelines.org Oct 2007.
Palefsky JM 2011.
Need for better biomarkers for
screening
• Anal cytology limitation
– Low sensitivity and poor correlation with histologic grading
• HRA limitation
– Expensive and very limited number of trained
physicians/nurses
• Potential HGAIN biomarkers
–
–
–
–
p16 and other cell cycle markers: immunocytochemistry
E6/E7 mRNA: flow cytometry
E6 oncoproteins: rapid test
HPV DNA detection: screening test/genotyping assay
Panther LA, et al. Clin Infect Dis. 2004;38:1490-1492.
Biomarkers for anal HSIL
Best for
Best for
prediction of detection
disease of disease
In the future at that visit
Phanuphak N, et al. (Submitted)
Treatment of anal HSIL
• Various “in-office” treatment options are available
• Side effects are not uncommon but manageable, some
concerns about long-term sexual functioning
• Treatment causes regression of lesions, although no
prove that it will prevent anal cancer
• Recurrence rate is substantial but usually is minimal
• Better treatment modalities are needed
Richel O, et al. Lancet Oncol 2012;14:346-53.
Fox PA. Sex Health 2012;9:628-31.
Treatment of anal cancer
• Combination chemoradiation as the first-line therapy
• In very selected cases, local excision may be used as
primary treatment, often with chemoradiation
• Salvage abdominoperineal resection for persistent or
recurrent anal cancers
Stage
Localised (confined to 1ry site)
5-year survival (%)
79.0
Regional (spread to regional LN)
Distant (metastasised)
58.5
29.6
Szmulowicz UM and Wu JS. Sex Health 2012;9:593-609.
SEER 2011.
Do I want to screen my patient?
YES
No
• What do you want to
screen for?
• More research is
needed on
– Anal cancer: Digital
ano-rectal exam
– Anal HSIL: Cytology+/HSIL biomarkers and
high-resolution
anoscopy
– Natural history of
anal HSIL
Do I want to treat anal HSIL in my
patient?
YES
No
• Use treatment
modalities currently
available
• More research is
needed on
• Frequent follow-up
• More research is
needed on
– Better treatment of
anal HSIL
– Natural history of
anal HSIL
– Anal cancer
biomarkers
– Better treatment of
anal HSIL and its side
effects
Summary
• HAART not reducing HPV-related cancers
– Some cancers increasing
• HIV+ men and women are more likely to have
HSIL than HIV- men and women
– High prevalence of anal HSIL in HIV+ MSM and
women
• Several challenges are there when considering
screening programs for anal HSIL
– Dependent on clinician’s interpretation of the data
and readiness of the local health systems
Acknowledgments
Thai Red Cross AIDS Research Centre
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Nipat Teeratakulpisarn
Praphan Phanuphak
Tippawan Pankam
Jiranuwat Barisri
TRC Anonymous Clinic staff
Our clinic clients & study participants
Chulalongkorn University
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HIV-NAT and SEARCH
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Jintanat Ananworanich
Steve Kerr
Cecilia Shikuma
Reshmie Ramautarsing
Srinakharinwirot University
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Piamkamon Vacharotayangkul
Somboon Keelawat
Surang Triratanachat
Surasith Chaithongwongwatthana
Preecha Ruangvejvorachai
Sarunya Numto
UCSF
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Joel Palefsky
TREAT Asia
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Annette Sohn
The AIN Biomarker Study is funded by the US NIH, through a grant to amfAR for the International
Epidemiologic Databases to Evaluate AIDS (IeDEA); NIAID/NCI/NICHD, UO1AI069907.