catching up on hpv-related cancers: diagnostic advances and treatment controversies
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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 - PowerPoint PPT PresentationTRANSCRIPT
Catching up on HPV-related cancers: diagnostic advances and treatment controversies
Nittaya Phanuphak, MD, PhDThai 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
1980-1989 1990-1995 1996-20040
100
200
300
400
500
177.3
448.9
70.989 90.4
In situ Invasive
Chaturvedi AK, et al. J Natl Cancer Inst 2009;101:1120-30.
SIR 8.9 for in situ cancer, 5.6 for invasive cancerIn
cide
nce
per 1
00,0
00 P
Y
1980-1989 1990-1995 1996-20040
102030405060708090
100
1.718.3
29.510.5
20.7
42.3
InvasiveIn situ
Anal cancer in HIV+ men and women
1980-1989 1990-1995 1996-20040
102030405060708090
100
0 1.7 5.20
5.2 11.2
Inci
denc
e pe
r 100
,000
PY
Chaturvedi AK, et al. J Natl Cancer Inst 2009;101:1120-30.
SIR In situ InvasiveMales 68.6 34.6 - MSM 89.7 51.8Women 33.0 14.5
MEN WOMEN
Oropharyngeal cancer in HIV+ men and women
1980-1989 1990-1995 1996-20040
10
20
30
40
50
0 3.96.5
Invasive
Chaturvedi AK, et al. J Natl Cancer Inst 2009;101:1120-30.
SIR 1.6
Inci
denc
e pe
r 100
,000
PY
HPV infection and dysplastic transformation
CancerNormal
Low-grade squamous
intraepithelial lesion (LSIL)
High-grade squamous
intraepithelial lesion (HSIL)
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• 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
NO• 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.
HPV in-fection
CIN0
20
40
60
80
100
35
1924
4
HPV infectionHPV in-fection
CIN0
20
40
60
80
10083
16
70
6
Any HPV typesHigh-risk HPV types
HPV infection
Cervical HPV and histologic HSIL among HIV+ women
• Progression of CIN 3 to cervical cancer = 1 in 80 per year
Prev
alen
ce (%
)
Histologic SIL
SUN (US) THAILAND
Histologic SIL
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.
All histologic SIL
Histologic HSIL
Cervical cancer rate in HIV+ women = 90 / 100,000
HPV in-fection
AIN0
20
40
60
80
100
14 9
HPV infectionHPV in-fection
AIN0
20
40
60
80
100 90
16
85
9
Any HPV typesHigh-risk HPV types
HPV infection
Anal HPV and histologic HSIL among HIV+ women
• Anal SIL is as common as cervical SIL• More common in women with cervical, vulvar, vaginal
high-grade diseases
Prev
alen
ce (%
)
SUN (US) THAILAND
Histologic SIL
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.
All histologic SIL
Histologic HSIL
Anal cancer rate in HIV+ women = 11 / 100,000
0
20
40
60
80
10085
5958
37
1911
HIV-positive
Anal HPV and histologic HSIL among HIV+ and HIV- MSM
• 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
Prev
alen
ce (%
)
HIV-negative
THAILAND
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.
0
20
40
60
80
10082
5861
40
Any HPV typesHigh-risk HPV types
HIV-positive
CHINA
0
20
40
60
80
100 93
6474
3729
22
Any HPV typesHigh-risk HPV types
HIV-positive
Meta-analysis
HIV-negative HIV-negative
Anal cancer rate in HIV+ MSM = 78 / 100,000 and in HIV- MSM = 5 / 100,000
Prev
alen
ce (%
)
Anal HSIL screening
New York State Department of Health AIDS Institute: www.hivguidelines.org Oct 2007.Palefsky JM 2011.
• 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
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
Phanuphak N, et al. (Submitted)
Best for detection of disease
at that visit
Best for prediction of disease
In the future
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
Szmulowicz UM and Wu JS. Sex Health 2012;9:593-609.SEER 2011.
Stage 5-year survival (%)Localised (confined to 1ry site) 79.0Regional (spread to regional LN) 58.5Distant (metastasised) 29.6
Do I want to screen my patient?
YES• What do you want to
screen for?– Anal cancer: Digital
ano-rectal exam– Anal HSIL: Cytology+/-
HSIL biomarkers and high-resolution anoscopy
No• More research is
needed on– Natural history of
anal HSIL
Do I want to treat anal HSIL in my patient?
YES• Use treatment
modalities currently available
• More research is needed on– Better treatment of
anal HSIL
No• Frequent follow-up• More research is
needed on– 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
AcknowledgmentsThai Red Cross AIDS Research Centre • Nipat Teeratakulpisarn• Praphan Phanuphak• Tippawan Pankam• Jiranuwat Barisri• TRC Anonymous Clinic staff• Our clinic clients & study participants
Chulalongkorn University• Somboon Keelawat• Surang Triratanachat• Surasith Chaithongwongwatthana• Preecha Ruangvejvorachai• Sarunya Numto
UCSF• Joel Palefsky
TREAT Asia• 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.
HIV-NAT and SEARCH• Jintanat Ananworanich• Steve Kerr• Cecilia Shikuma• Reshmie Ramautarsing
Srinakharinwirot University• Piamkamon Vacharotayangkul