PRO: SHOULD WOMEN BE SCREENED FOR ANAL CANCER?

Anna-Barbara Moscicki, MD. University of California, San Francisco

Fuente: PRO: SHOULD WOMEN BE SCREENED FOR ANAL CANCER?
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I have the following financial relationships with the manufacturer(s) of any commercial product(s) and/or provider of commercial services discussed in this Ce activity:
  • GlaxoSmithKline
  • Advisory Board, Research Funds
  • Merck
  • Advisory Board

RATES OF ANAL CANCER IN THE U.S.

  • Worldwide1
  • U.S.2
  • Women
  • Men
  • Women
  • Men
  • 14,500
  • 13,500
  • 3,190
  • 2,100

1 Chaturuedi A et al, JAHC 2010
2 Am Ca Soc 2009
THE INCIDENCE OF HPV-RELATED CANCERS IS INCREASING
Graph
Parkin DM et al., CA Cancer J Clin 2005
AGE-SPECIFIC INCIDENCE OF INVASIVE SQUAMOUS CELL ANAL CANCER BY SEX AND RACE/ETHNICITY, UNITED STATES, 1998-2003

Graph

PREVALENCE OF THE MOST COMMON HPV TYPE (TYPE-SPECIFIC PREVALENCE ESTIMATES ARE RESTRICTED TO STUDIES THAT OBTAINED HPV DNA FROM BIOPSIES AND TYPED FOR AT LEAST HPV 16 AND HPV 18) IN BIOPSY SPECIMENS OF INVASIVE ANAL CANCER (N5 810), HSIL (N5 178), AND LSIL (LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESIONS, LSIL ESTIMATES INCLUDE ONLY 2 BIOPSIED CASES FROM WOMEN.) (N 5 49)

Graph

Hoots BE et al, Int J Cancer 2009


CUMULATIVE INCIDENCE OF ANAL HPV INFECTIONS IN WOMEN

Graph

Goodman MT et al, JID 2008


RISK FOR ANAL CANCERS
  • HIV infection
  • Cervical cancer / CIN3
  • Vulvar / vaginal cancer
  • Practice regular anal intercourse

RELATIVE RISKS (BY AGE OF AIDS ONSET) OF HPV-ASSOCIATED ANOGENITAL CANCERS AMONG 309,365 PATIENTS WITH AIDS INVASIVE CANCERS

Relative risk (95% C.I.)



  • Age at AIDS onset, y
  • Anus (men)
  • Anus (women)
  • <30
  • 162.7 (103.1 – 244.0)
  • 134.3 (16.3 – 484.8)
  • 30-39
  • 40.1 (31.2 – 50.8)
  • 12.2 (2.5 – 35.7)
  • 40-49
  • 39.3 (31.3 – 48.7)
  • 2.8 (0.1 – 15.6)
  • >50
  • 23.4 (16.6 – 32.0)
  • 2.4 (0.1 – 13.5)
  • All
  • 37.9 (33.0 – 43.4)
  • 6.8 (2.7 – 14.0)

Frisch M et al, JNCI 2000
ANNUAL INCIDENCE RATES OF 3 AIDS-DEFINING (TOP ROW) AND 9 NON-AIDS-DEFINING TYPES OF CANCER AMONG HIV-INFECTED PERSONS AND THE GENERAL POPULATION

Graph

Patel et al, Ann Int Med 2008


RISK OF DEVELOPING SUBSEQUENT CANCER AFTER CANCER OF THE CERVIX (SEER 1973-2000)
  • Cumulative incidence of developing a second cancer among 30,563 who survived 2 or more months was 13.2% at 25 years (adjusted for competing causes of death)
  • Higher in younger women at dx
  • Higher in those who received radiotherapy
  • Higher in blacks

New malignancies among cancer survivors: SEER 1973-2000

SIGNIFICANT INCREASES INCLUDED

  • Tobacco-related (e.g. lung, bronchitis, buccal cavity, bladder)
  • HPV-related (anus, vagina, vulva, tonsils, pharynx)
  • Radiotherapy (bladder, ovary, vagina, vulva, bone, rectum)

New malignancies among cancer survivors: SEER 1973-2000

RISK OF SUBSEQUENT PRIMARY ANAL CANCERS AFTER PRIMARY CANCER OF THE CERVIX, VAGINA, AND VULVA


  • Primary
  • -
  • Cervix
  • EAR
  • Vagina
  • EAR
  • Vulva
  • EAR
  • -
  • O/E
  • -
  • O/E
  • -
  • O/E
  • -
  • Anus
  • 3.24*
  • 0.53
  • (3.18)
  • 0.79
  • 8.04*
  • 2.89
  • Cx
  • -
  • -
  • (2.52)
  • -
  • (1.52)
  • -
  • Vagina
  • 16.87*
  • -
  • -
  • -
  • 6.12*
  • -
  • Vulva
  • 5.12*
  • -
  • 8.06*
  • -
  • -
  • -
  • Tonsils
  • 3.92*
  • -
  • (0)
  • -
  • (1.59)
  • -
  • *p=<0.05; ( ) = NS; O/E = observed / expected; EAR = excess absolute risk per 10,000 person-years

New malignancies among cancer survivors: SEER 1973-2000
RISK (O/E) OF ANAL CANCER AFTER CANCER OF THE CERVIX (SEER 1973-2000)

  • Years After 1st primary cervical cancer
  • < 1
  • 1-4
  • 5-9
  • 10-14
  • (0)
  • (2.61)
  • 3.32*
  • 5.21*
  • Age (yrs) of cervical cancer diagnosed
  • < 50
  • > 50
  • > 70
  • -
  • 4.13*
  • 3.41*
  • NS
  • -
  • O/E = observed / expected

New malignancies among cancer survivors: SEER 1973-2000
RISK (O/E) OF ANAL CANCER AFTER CANCER OF THE VULVA (SEER 1973-2000)

  • Years After 1st primary cervical cancer
  • < 1
  • 1-4
  • 5-9
  • 10-14
  • 12.44*
  • 7.40**
  • (2.39)
  • 13.4
  • Age (yrs) of cervical cancer diagnosed
  • -
  • < 50
  • > 55
  • -
  • -
  • 22.02*
  • 5.53*
  • -
  • O/E = observed / expected

New malignancies among cancer survivors: SEER 1973-2000
RISK OF ANAL, VAGINAL, AND VULVAR CANCER IN WOMEN WITH CIN3: PROSPECTIVE POPULATION-BASED STUDY IN SWEDEN (1968-2004)

  • -
  • Adjusted IRR*
  • Anal
  • 4.68 (3.9 – 5.6)
  • Vaginal
  • 6.74 (5.2 – 8.6)
  • Vulvar
  • 2.22 (1.8 – 2.7)
  • Adjusted for age, time period, SES, and parity; *IRR= incident risk ratio

Edgren and Sparen, Lancet Onc 2007

RISK OF CANCER OF THE ANUS OF WOMEN WITH A HISTORY OF GRADE 3 CIN COMPARED WITH THOSE WITHOUT SUCH HISTORY, STRATIFIED BY ATTAINED AGE


  • -
  • Anal cancer
  • -
  • IRR (95% CI)
  • 18-29 years
  • -
  • CIN 3 history
  • 31.09 (3.74 – 258.44)
  • 30-39 years
  • -
  • CIN 3 history
  • 7.59 (3.35 – 17.20)
  • 40-49 years
  • -
  • CIN 3 history
  • 5.82 (3.87 – 8.75)
  • 50-59 years
  • -
  • CIN 3 history
  • 4.70 (3.40 – 6.50)
  • >60 years
  • -
  • CIN 3 history
  • 3.97 (2.96 – 5.32)

IRR= incident risk ratio
Edgren G et al, Lancet Onc 2007

RISK OF CANCER OF THE ANUS OF WOMEN WITH A HISTORY OF GRADE 3 CIN COMPARED WITH THOSE WITHOUT SUCH HISTORY, STRATIFIED BY TIME SINCE FIRST DIAGNOSIS


  • Anal cancer
  • -
  • Events (n
  • IRR (95% CI)
  • <1 year
  • 0
  • 0.00 (0.00 – 2.06)*
  • 1-4 years
  • 4
  • 1.67 (0.41 – 4.36)
  • 5-9 years
  • 12
  • 3.90 (2.08 – 6.60)
  • >10 years
  • 115
  • 4.98 (4.07 – 6.04)
  • No CIN 3 history
  • 857
  • 1.00

*For reasons of model convergence, these estimates could not be estimated in the multivariate model and are therefore taken from the univariate model. Adjusted for attained age, calendar period, socioeconomic status, and parity. The number of person-years may not add up because of rounding. Reference category is no CIN 3 history. IRR= incident rate ratios

Edgren G et al, Lancet Onc 2007


AGE-SPECIFIC INCIDENCES OF VAGINAL, VULVAR, ANAL, AND RECTAL CANCER IN WOMEN WITH AND WITHOUT A HISTORY OF GRADE3 3 CIN

Graph

Edgren G et al, Lancet Onc 2007


STANDARDIZED INCIDENCE RATIO OF ANAL CANCER IN PATIENTS WITH IN SITU AND INVASIVE GYNECOLOGIC NEOPLASM (SEER 1973-2000)

  • Primary Gynecologic Neoplasm
  • Race
  • Observed
  • Expected*
  • Standardized Incidence Ratio
  • 95% CIa
  • Cervical
  • -
  • -
  • -
  • -
  • -
  • In situ
  • Total
  • 137
  • 8.4
  • 16.4
  • 13.7 – 19.2
  • Invasive
  • Total
  • 28
  • 4.5
  • 6.2
  • 4.1 – 8.7
  • Vulvar
  • -
  • -
  • -
  • -
  • -
  • In situ
  • Total
  • 55
  • 2.5
  • 22.2
  • 16.7 – 28.4
  • Invasive
  • Total
  • 28
  • 1.6
  • 11.5 – 24.4
  • Vaginal
  • -
  • -
  • -
  • -
  • -
  • In situ
  • Total
  • 5
  • 0.7
  • 7.6
  • 2.4 – 15.6
  • Invasive
  • Total
  • <5b
  • <5b
  • 1.8
  • 0.2 – 5.3

CI, confidence interval

*The expected cases were calculated from Surveillance, Epidemiology and End Results 9, stratified by age, race and calendar-year group.

a The CI was calculated using the Vanderbroucks method.

b These data hidden as per our data-use agreement with the Surveillance, Epidemiology and End Results program.

Saleem AM et al, OB GYN 2011


SO?

CAN WE PICK UP PRECURSORS OF ANAL CANCER?

FOCAL HGAIN (?) IN TEEN STUDY PT

Image (cervix)

PREVALENCE OF AIN IN SPECIFIC POPULATIONS

Healthy women 4 – 6 % 1,2

CIN 3 7% 3

CIN + VIN / Vulvar Ca 21% 3

HIV 21 – 24% 2,5

Renal transplants 6% 4

1 Moscicki AB et al, Ca Epi Biomarker Prev 1999; 2 Moscicki AB et al, AIDS 2003; 3 Park et al, Gynecol Oncol 2009; 4 Patel et al, Br J Surg 2010; 5 Hessol NA et al, AIDS 2009


RISK FACTORS FOR ABNORMAL ANAL CYTOLOGY

  • Healthy women
  • Immunocompromised
  • Anal intercourse1,11
  • Anal intercourse4,6,7
  • Smoking10
  • Smoking19
  • Genital warts1
  • Genital warts7
  • Abnormal cervical cytology1,2
  • Abnormal cervical cytology5
  • No. Lifetime partners2
  • Low CDV (<200)4,5,9

1 Moscicki AB et al, Ca Epi Biomarker Prev 1999; 2 Moscicki AB et al, AIDS 2003; 4 Conley et al, JID 2010; 5 Tandon et al, Am J Obstet Gyn 2010; 6 Hessol NA et al, AIDS 2009; 7 Patel et al, Br J Surg 2010; 8 Park et al, Gynecol Oncol 2009, 9 Durante et al, CEBP 2003; 10 Etienney I et al, Dis Colon Rectum 2008; 11 Jacyntho CM et al, Am J Obstet Gyn 2011


ANAL CANCER SCREENING COULD BE LIFE-SAVING
  • HIV
  • Cervical cancer / CIN 3
  • Vulvar cancer
  • ?? Practice regular anal intercourse
QUALITY-ADJUSTED LIFE YEARS AND INCREMENTAL COST-EFFECTIVENESS RATIOS FOR ANAL CANCER SCREENING STARTEGIES IN WOMEN WITH HIV

  • -
  • No screening
  • Annual
  • Biennial
  • Total cost*
  • $2,832,937
  • $3,314,789
  • $2,986,947
  • QALYs
  • 352.9
  • 357.3
  • 357.3
  • ICER**
  • -
  • $108,763
  • $34,763
  • Discounted
  • -
  • $112,026
  • $35,806

*Cost of screening strategy for 100 women during a 5-year cycle

** Incremental cost-effectiveness ratio determined by (total cost of screening strategy – total cost of no screening) / QALYs no screening

Lazenby GB et al, JLGTD 2012


PRO:
  • HIV-infected women > 25 years
  • CD4 < 200
  • Women who engage in anal intercourse regularly – highest risk

CERVICAL CANCER / CIN 3
  • All women starting at 5 years after Dx
  • Younger age at Dx: higher the risk
  • Women who engage in anal intercourse regularly

VULVAR CANCER
  • All women starting at time of Dx
  • Younger age at Dx: higher risk