Advances in the Screening, Advances in the Screening, Diagnosis, and Treatment Diagnosis, and Treatment

of Cervical Diseaseof Cervical Disease

1. Walboomers et al. J Pathol. 1999;189:12-19.

2. American Cancer Society, Cancer Facts & Figures 2002.3. Chu KC et al. Cancer. 1999;86:157-169.

Cervical CancerCervical Cancer

• Second most common cancer among women worldwideSecond most common cancer among women worldwide11

• The American Cancer Society estimates that in 2002, ~13,000 new cases of invasive cervical cancer will be diagnosed in the United States, with about 4,100 deaths2 . In 2001, the estimates were ~ 12,900 cases and 4,500 deaths.

• 75% decreased incidence and 73% decreased mortality since Pap screening began in 1949

• However, cervical cancer mortality has not declined in the US However, cervical cancer mortality has not declined in the US since the 1980s since the 1980s 33

Cervical Cancer StatisticsCervical Cancer StatisticsYearsYears DescriptionDescription U.S. U.S. StatisticStatistic

19981998 Death rate from cervical cancerDeath rate from cervical cancer22 3.0 per 100,000 women3.0 per 100,000 women

20002000 Cervical cancer deathsCervical cancer deaths22 ~ 4,600~ 4,600

20012001 Cervical cancer deathsCervical cancer deaths11 ~ 4,400~ 4,400

1955 - 19921955 - 1992 Change in the number of cervical cancer deathsChange in the number of cervical cancer deaths11 74%74%

1973 - 19811973 - 1981 Annual change in invasive cervical cancer mortalityAnnual change in invasive cervical cancer mortality33 4.6%4.6%

1981 - 19981981 - 1998 Annual change in invasive cervical cancer mortalityAnnual change in invasive cervical cancer mortality33 1.6%1.6%

1992 - 19981992 - 1998 Incidence of invasive cervical cancer (overall)Incidence of invasive cervical cancer (overall) 3 3 8.7 per 100,000 women8.7 per 100,000 women

1992 - 19981992 - 1998 Incidence of invasive cervical cancer by race:Incidence of invasive cervical cancer by race: 3 3

White White

BlackBlack

Asian/Pacific IslanderAsian/Pacific Islander

American Indian/Alaskan NationalAmerican Indian/Alaskan National

HispanicHispanic

8.1 per 100,000 women8.1 per 100,000 women

11.0 per 100,000 women11.0 per 100,000 women

10.3 per 100,000 women10.3 per 100,000 women

6.4 per 100,000 women6.4 per 100,000 women

14.4 per 100,000 women14.4 per 100,000 women

1973 - 19811973 - 1981 Annual change in invasive cervical cancer incidenceAnnual change in invasive cervical cancer incidence33 4.8%4.8%

1981 - 19981981 - 1998 Annual change in invasive cervical cancer incidenceAnnual change in invasive cervical cancer incidence33 1.1%1.1%

20002000 New diagnoses of cervical cancerNew diagnoses of cervical cancer22 ~ 12,800~ 12,800

20012001 New diagnoses of cervical cancerNew diagnoses of cervical cancer11 ~ 12,900~ 12,900

U.S. Trends in Cervical Cancer U.S. Trends in Cervical Cancer Morbidity and MortalityMorbidity and Mortality

Year

Source: National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) data,

American Cancer Society 2001.

Nu

mb

er o

f C

ases

Nu

mb

er o

f C

ases

20,000

1970 1975 1980 1985 19951990

15,000

10,000

5,000

Source: Vizcaino AP et al. Int J Cancer. 1998;75:536-545.

SEER Trends in North American Incidence SEER Trends in North American Incidence of Cervical of Cervical AdenocarcinomaAdenocarcinoma

Cu

mu

lati

ve R

ate

per

100

0 C

um

ula

tive

Rat

e p

er 1

000

Wo

men

Wo

men

Black, USABlack, USA

White, USAWhite, USA

CanadaCanada

Hispanic, USAHispanic, USA

Year of BirthYear of Birth

00

0.050.05

0.100.10

0.150.15

0.200.20

0.250.25

0.300.30

19301930 19401940 19501950 19601960

Risk Factors Associated With Risk Factors Associated With Precancerous Changes and Cancer of Precancerous Changes and Cancer of

the Cervixthe Cervix • Human Human papillomavirus (HPV) infectionpapillomavirus (HPV) infection

• Sexual activity: multiple partners; begun at an early Sexual activity: multiple partners; begun at an early age age

• ParityParity

• Human immunodeficiency virus (HIV)Human immunodeficiency virus (HIV)

• Immunosuppressed statusImmunosuppressed status

• SmokingSmoking

• History of other sexually transmitted diseases History of other sexually transmitted diseases –e.g., Herpes simplex, Chlamydia, bacterial –e.g., Herpes simplex, Chlamydia, bacterial vaginosisvaginosis

• Oral contraceptive useOral contraceptive use

• Low socioeconomic statusLow socioeconomic status

• Poor diet–e.g., vitamin deficiencyPoor diet–e.g., vitamin deficiency

• AlcoholismAlcoholism

Cervical Epithelium Showing Cervical Epithelium Showing Progressive Degrees of Dysplasia and Progressive Degrees of Dysplasia and

NeoplasiaNeoplasia

Basement membrane

Normal Mild Moderate Severe Carcinoma squamous in situ epithelium Dysplasia

HSIL

Koilocytosis CIN1 CIN2 CIN3

LSIL

Natural History of Cervical LesionsNatural History of Cervical Lesions

Biopsy Regress Persist Progress Progress Result to CIS to Invasion

CIN1 57% 32% 11% 1%

CIN2 43% 35% 22% 5%

CIN3 32% <56% -- >12%

Source: ÖstÖr AG. Int J Gynecol Pathol. 1993;12(2):186-192.

Natural History of Cervical LesionsNatural History of Cervical Lesions

Source: Melnikow J et al. Obstet Gynecol. 1998;92(4Pt2):727-735.

ASCUS 68.19% (57.51, 78.86) 7.13% (0.8, 13.5) 0.25% (0, 2.25)

LSIL 47.39% (35.92, 58.86) 20.81% (6.08, 35.55) 0.15% (0, 0.71)

HSIL 35.03% (16.57, 53.49) 23.37% (12.82, 32.92) 1.44% (0, 3.95)

Pap Regress Progress to/ Progress to Diagnosis to Normal Persist as HSIL Invasive Cancer

(95% CI) in 24 months in 24 months (95% CI) (95% CI)

ProgressionMild to moderate or worse 11.1% 20.4% 28.8%Mild to severe or worse 2.1% 5.5% 9.9%Moderate to severe or worse 16.3% 25.1% 32.0%

RegressionMild to first normal Pap 44.3% 74.0% 87.7%Moderate to first normal Pap 33.0% 63.1% 82.9%Mild to second normal Pap 8.7% 39.1% 62.2%Moderate to second normal Pap 6.9% 29.0% 53.7%

Grade of Dysplasia Within 2 years Within 5 years Within 10 years

Progression and Regression Progression and Regression of Cervical Lesionsof Cervical Lesions

Source: Holowaty P et al. J Natl Cancer Inst. 1999;91(3):252-258.

Mean Age at Diagnosis of Cervical LesionsMean Age at Diagnosis of Cervical Lesions

Carcinoma 56.4 Postmenopausal Premenopausal (61.9%) (32.4%)

HSIL 33.8 Premenopausal Postmenopausal (72.2%) (10.7%)

LSIL 30.8 Premenopausal Pregnant (74.4%) (10.2%)

Glandular 48.2 Premenopausal PostmenopausalIntraepithelial (50.3%) (38.5%)Lesion

Diagnosis Mean Patient Predominant Second Most Age (Years) Patient Status Prevalent Patient

Status

Source: Jones BA et al. Arch Pathol Lab Med. 2000;124:665-671.

Cervical Cancer Screening Guidelines:Cervical Cancer Screening Guidelines:American Cancer Society

• All women should have yearly Pap smears starting at age 18 or when they begin having sex, whichever occurs first

• The doctor may decide to do the test less often if a woman has had 3 normal tests in a row

• If a hysterectomy was done for cancer, more frequent Pap tests may be recommended

• Women who have had their uterus removed and those past menopause still need to have regular Pap tests

Bethesda System 2001Bethesda System 2001

Specimen Type: Indicate conventional Pap smear vs. liquid-based vs. other

Specimen Adequacy• Satisfactory for evaluation (describe presence or absence of

endocervical/transformation zone component and any other quality indicators--e.g., partially obscuring blood, inflammation, etc.)

• Unsatisfactory for evaluation (specify reason)– Specimen rejected/not processed (specify reason)

– Specimen processed and examined, but unsatisfactory for evaluation of epithelial abnormality because of (specify reason)

General Categorization (optional)• Negative for intraepithelial lesion or malignancy

• Epithelial cell abnormality: See interpretation/result (specify “squamous” or “glandular” as appropriate)

• Other: See interpretation/result (e.g., endometrial cells in a woman 40 years of age)

Automated Review: If case examined by automated device, specify device and result

Ancillary Testing: Provide a brief description of the test methods and report the result so that it is easily understood by the clinician

 

Bethesda System 2001Bethesda System 2001 (continued)(continued)

Interpretation/Result• Negative for Intraepithelial Lesion or Malignancy (when there is

no cellular evidence of neoplasia, state this in the General Categorization above and/or in the Interpretation/Result section of the report, whether or not there are organisms or other non-neoplastic findings)

Organisms– Trichomonas vaginalis– Fungal organisms morphologically consistent with Candida spp– Shift in flora suggestive of bacterial vaginosis– Bacteria morphologically consistent with Actinomyces spp.– Cellular changes consistent with Herpes simplex virus

Other Non-Neoplastic Findings (optional to report; list not inclusive):– Reactive cellular changes associated with

• Inflammation (includes typical repair)• Radiation• Intrauterine contraceptive device (IUD)

– Glandular cells status post hysterectomy– Atrophy

 

Bethesda System 2001Bethesda System 2001 (continued)(continued)

Bethesda System 2001Bethesda System 2001 (continued)(continued)

• Other (list not inclusive)– Endometrial cells (in a woman 40 years of age)

(specify if ‘negative for squamous epithelial lesion’) • Epithelial Cell Abnormalities

– Squamous Cell• Atypical squamous cells

– Of undetermined significance (ASC-US)– Cannot exclude HSIL (ASC-H)

• Low-grade squamous intraepithelial lesion (LSIL)– Encompassing: HPV/mild dysplasia/CIN1

• High-grade squamous intraepithelial lesion (HSIL) – Encompassing: moderate and severe dysplasia, CIS/CIN2 and

CIN3– With features suspicious for invasion (if invasion suspected)

• Squamous cell carcinoma

Bethesda System 2001Bethesda System 2001 (continued)(continued)

– Glandular Cell• Atypical

– Endocervical cells (NOS* or specify in comments)– Endometrial cells (NOS or specify in comments)– Glandular cells (NOS or specify in comments)

• Atypical– Endocervical cells, favor neoplastic– Glandular cells, favor neoplastic

• Endocervical adenocarcinoma in situ• Adenocarcinoma

– Endocervical– Endometrial– Extra uterine– NOS

 – Other Malignant Neoplasms: (specify)

* NOS = Not otherwise specified

Educational Notes and Suggestions: (optional) Suggestions should be concise and consistent with clinical follow-up

guidelines published by professional organizations (references to relevant publications may be included)

Bethesda System 2001Bethesda System 2001 (continued)(continued)

Bethesda 2001 ChangesBethesda 2001 Changes

• Satisfactory: Liquid-based—minimum 5,000 epithelial cells; Satisfactory: Liquid-based—minimum 5,000 epithelial cells; presence of epithelial cell abnormalitypresence of epithelial cell abnormality

• ““SBLB” eliminatedSBLB” eliminated

• Unsatisfactory: specimen rejected/not processed; or specimen Unsatisfactory: specimen rejected/not processed; or specimen processed/examined, but unsatisfactory because of (specify processed/examined, but unsatisfactory because of (specify reason)reason)

• WNL WNL and BCC are now Negative for Intraepithelial Lesions or and BCC are now Negative for Intraepithelial Lesions or Malignancy; includes BCC (e.g., organisms and reactive changes) Malignancy; includes BCC (e.g., organisms and reactive changes) as descriptor onlyas descriptor only

• The multiple subcategories of ASCUS have been reduced to ASC-The multiple subcategories of ASCUS have been reduced to ASC-US or ASC-H, with no other modifiersUS or ASC-H, with no other modifiers

• The subcategories of AGUS (now AGC) have been expandedThe subcategories of AGUS (now AGC) have been expanded to to allow for a more descriptive diagnosis of glandular abnormalities; allow for a more descriptive diagnosis of glandular abnormalities; AIS is now a distinct subcategoryAIS is now a distinct subcategory

The Bethesda System 2001The Bethesda System 2001

• LSIL = HPV / mild dysplasia / CIN1LSIL = HPV / mild dysplasia / CIN1

• HSIL = moderate and severe dysplasia / CIS / CIN2 and HSIL = moderate and severe dysplasia / CIS / CIN2 and CIN3CIN3

• ASCUS = ASC-US (undetermined significance) orASCUS = ASC-US (undetermined significance) or

ASC-H (cannot exclude HSIL)ASC-H (cannot exclude HSIL)

Annual Number of Women with Abnormal Pap Results in the US

LSIL

Cancers

HSIL

22 - 3 million- 3 million

1.25 million1.25 million

300,000300,000

12,80012,800

ASC

AGC 180,000-300,000180,000-300,000

Source: J. Thomas Cox, with permission.

Mean Sensitivity of Conventional Pap Smear (%), 95% CIMean Sensitivity of Conventional Pap Smear (%), 95% CI

Sensitivity of the Pap SmearSensitivity of the Pap Smear

1. Agency for Health Care Policy and Research (AHCPR). Evaluation of Cervical Cytology. 1999. 2. Fahey MT et al. Am J Epidemiol. 1995;141:680-689.

Two Types of ScreeningTwo Types of Screening

Conventional Pap SmearConventional Pap Smear• Cervical cell sample manually “smeared” onto slide for Cervical cell sample manually “smeared” onto slide for

screeningscreening

Liquid-BasedLiquid-Based• Cervical cell sample put into liquid medium for Cervical cell sample put into liquid medium for

suspension before automated thin layer/monolayer suspension before automated thin layer/monolayer slide preparationslide preparation

– ThinPrepThinPrep®® 2000 System 2000 System

– SurePathSurePathTMTM (formerly AutoCyte (formerly AutoCyte®® PREP) PREP)

Conventional Pap SmearConventional Pap Smear

* From ThinPrep Sampling Study, Hutchinson 1994

Overcoming the Inherent Limitations Overcoming the Inherent Limitations of the Conventional Pap Smearof the Conventional Pap Smear

Majority of cells not capturedMajority of cells not captured Non-representative transfer Non-representative transfer

of cellsof cells Clumping and overlapping of Clumping and overlapping of

cellscells Obscuring materialObscuring material

Virtually all cells of sample are Virtually all cells of sample are collectedcollected

Randomized, representative Randomized, representative transfer of cellstransfer of cells

Even distribution of cellsEven distribution of cells Minimizes obscuring materialMinimizes obscuring material

Liquid-based Cytology*Liquid-based Cytology*

ThinPrep® Pap Test SurePath™

Overview of Liquid-Based Cytology:Overview of Liquid-Based Cytology:FDA LabelingFDA Labeling

•

• Used as a replacement for the conventional Pap smear

• Specimen quality is significantly improved over that of the conventional Pap smear in a variety of patient populations

• Significantly more effective than the conventional Pap smear for the detection of low-grade and more severe lesions in a variety of patient populations

• Specimens should be collected using a broom-type or endocervical brush/spatula combination collection device

• Increased HSIL+ detection by 59.7% (data from a multi-site, historical control study)

• Approved as a specimen medium for HPV DNA testing using Digene Hybrid Capture® 2, as well as for chlamydia and gonorrhea screening

• Used as a replacement for the conventional Pap smear

• Significantly fewer Unsatisfactory and SBLB cases as compared to the conventional Pap smear

• Provides similar results to the conventional Pap smear (data from a prospective split-sample comparison in a variety of patient populations and laboratory settings)

• Specimens should be collected using a broom-type sampling device

ThinPrep® Pap Test Package Insert, Cytyc CorporationAutoCyte PREPTM SYSTEM package insert (now SurePathTM), TriPath Imaging, Inc.

HSIL+ Clinical Outcomes TrialHSIL+ Clinical Outcomes Trial• Direct-to-vial study to evaluate ThinPrep 2000 vs. Direct-to-vial study to evaluate ThinPrep 2000 vs.

conventional Pap for the detection of high-grade conventional Pap for the detection of high-grade squamous and more severe lesions (HSIL+)squamous and more severe lesions (HSIL+)

• 10 metropolitan academic hospitals, two groups of 10 metropolitan academic hospitals, two groups of subjects per site:subjects per site:

– Routine screening populationRoutine screening population

– Referred for colposcopy Referred for colposcopy

• ThinPrep specimens (n = 10,226) collected prospectively ThinPrep specimens (n = 10,226) collected prospectively compared to historical control cohort (n = 20,917)compared to historical control cohort (n = 20,917)

• These sites demonstrated a 59.7% (These sites demonstrated a 59.7% (p p << 0.0010.001) increase ) increase in detection of HSIL+ lesions for ThinPrep specimensin detection of HSIL+ lesions for ThinPrep specimens

HPV Testing – Essential FactsHPV Testing – Essential Facts

• HPV is the major etiologic agent HPV is the major etiologic agent for cervicalfor cervical cancer cancer

• HPV detection is associated with an increased risk of HPV detection is associated with an increased risk of high-grade CINhigh-grade CIN

• Essentially all women with CIEssentially all women with CIN3 N3 have detectable HPV have detectable HPV DNA DNA

• Persistent infection with high-risk HPV is necessary Persistent infection with high-risk HPV is necessary for development and maintenance of CIN3 for development and maintenance of CIN3

• HPV testingHPV testing helps to clarify ambiguous cytology helps to clarify ambiguous cytology results and identifies persistent infection in women results and identifies persistent infection in women over 30over 30

HPV Risk TypesHPV Risk Types

Hybrid CaptureHybrid Capture®®2 2 (HC II)(HC II) HPV DNA Test uses two HPV DNA Test uses two RNA Probe cocktails to differentiate between RNA Probe cocktails to differentiate between carcinogenic and low-risk HPV types:carcinogenic and low-risk HPV types:

Low-risk

6 11 42 43 44

High-risk

16 18 31 33 35 39 45 51 52 56 58 59 68

HPV Prevalence and Cervical Cancer - HPV Prevalence and Cervical Cancer - Incidence by AgeIncidence by Age 1,21,2

Age (Years)

HP

V P

reva

len

ce (

%)

40-4415-19 20-24 25-29 30-34 35-39 45-49 50-54

0

5

10

15

20

25

30

0

5

10

15

20

25

30

Can

cer

inci

den

ce p

er 1

00,0

00

1. Sellors et al. CMAJ. 2000;163:503.2. Ries et al. Surveillance, Epidemiology and End Results (SEER) Cancer Stats NCI, 1973-1997. 2000.

HSIL 0.3% SIL+ 2.5% 0.51%

LSIL 0.9% -- 1.97%

ASCUS 3.5% 5.7% 2.8%

AGUS 0.5% 0.5% --

Pap Smear Incidence Incidence IncidenceCytology (Manos et al) (Chhieng et al) (Stoler)

Incidence of Atypical FindingsIncidence of Atypical Findings

1. Manos MM, Kinney WK, Hurley LB, et al. J Am Med Assoc 1999;281(17):1605-1610.2. Chhieng DC, Elgert PA, Cangiarella JF, et al. Acta Cytol 2000;44(4):557-566.3. Stoler MH. Mod Pathol 2000;13(3):275-284.

Comparison of HPV Testing and Repeat Comparison of HPV Testing and Repeat Pap in the Management of ASCUSPap in the Management of ASCUS

Based on HPV Test b 39.5% 89.2% 15.1%

Based on Repeat PapResultc 38.9% 76.2% 12.9%

Triage Referred to Sensitivity PPV for

Strategy Colposcopya for HSIL+ HSIL+

PPV = positive predictive value

Notes:a. Prevalence of positive test result in women with ASCUSb. Referral to colposcopy based on positive DNA test for high-risk HPV types, from specimen on initial visitc. Referral to colposcopy based on repeat Pap test result of ASCUS or more severe

Source: Manos et al, JAMA. 1999;281(17):1605-1610. 1999;281(17):1605-1610.

ALTS Study DesignALTS Study Design

• Randomized trial sponsored by NCI, 1995-2001Randomized trial sponsored by NCI, 1995-2001

• Enrolled 3488 women with community-based Enrolled 3488 women with community-based ASCUS and 1572 with LSIL results, randomized to ASCUS and 1572 with LSIL results, randomized to three management arms: three management arms:

– Immediate colposcopyImmediate colposcopy

– HPV triageHPV triage

– Repeat cytologyRepeat cytology

• Clinical follow-up every 6 months for 2-year periodClinical follow-up every 6 months for 2-year period

• LSIL arm discontinued due to limited utility of LSIL arm discontinued due to limited utility of positive test resultpositive test result

Source: Solomon D et al. J Natl Cancer Inst. 2001;93:293-299.

Sensitivity for CIN2+ by HC II & Pap Sensitivity for CIN2+ by HC II & Pap by Ageby Age

Clinical Center Pap 18-22 23-28 29+

Cutpoint %(+) / Sens %(+) / Sens %(+) / Sens

HC II 71 / 98 65 / 96 31 /

94

ASCUS+ 66 / 83 63 / 88 50 / 87

Sherman M, Schiffman M, Cox JT. J Nat Cancer Inst. 2001

Risk of CIN 2/3+ for ASC referralRisk of CIN 2/3+ for ASC referral Based on HPV status at enrollmentBased on HPV status at enrollment

Positive Negative ASCUS

Cox 17% 0.74% 6.9%1995 (14/81) (1/136) (15/217)

Manos 15% 1.2% 6.4%1999 (45/300) (6/498) (51/801)

ALTS 20.1% 1.1% 11.9%2001 (136/651) (6/541) (142/1192)

Total 17.9% 1.1% 9.4% (195/1087) (13/1175) (208/2210)

HPV HPV Total risk

Cox JT, et al. Am J Obstet Gynecol. 1995 Mar;172(3):946-54.Solomon D, et al. J Natl Cancer Inst. 2001;93:293-299.Manos et al, JAMA. 1999;281(17):1605-1610.

Primary Findings: ALTSPrimary Findings: ALTS

Management Sensitivity %* Referral % PPV % NPV % Modality

*For detection of (CIN2+)

Adapted from table 5, Solomon D et al. J Natl Cancer Inst. 2001;93:293-299.

Colposcopy 100 100 11 100

HPV 96 56 20 99

Cytology ASC-US+ 85 59 17 96

Cytology LSIL+ 59 26 26 94

Cytology HSIL+ 35 8 58 92

PPV = positive predictive value; NPV = negative predictive value

ASCCP Consensus Guidelines for the Management of Abnormal Cervical

Cytology and Cervical Cancer Precursors

• Held in Sept. 2001, NCI campus, 29 national and international organizations including ACS, NCI, CDC, ACOG, all the major cytopathology organizations, etc.

• The guidelines were all evidence-based (to the limits of the literature)

• They were placed on the Consensus Guidelines Website twice during the 6 months prior to the conference for public comment and appropriate revisions were made

• All of the guidelines were approved by a majority and most were approved by 70-90%

Valentina Jelincic

The monograph starts out with the ASC-H algorithm. Perhaps slide #39 should be moved here for the same flow.

AGC Rate SIL AIS CA

Jones BA, Novis DA. Follow-up of abnormal cervical cytology: a College of American Pathologists Q Probes Study of 16,132 cases from 306 laboratories. Arch Pathol Lab Med. 2000;124:672-681. (1-C)

0.3% 40% 5.8% 5.5%

AGC Findings from 306 LaboratoriesParticipating in CAP Survey 2000

Qualifier Any High-grade Lesion High-grade Glandular Lesion Only

AGUS reactive 5 – 39% 1 – 8%

AGUS NOS 9 – 41% 0 – 15%

AGUS neoplastic 27 – 96% 10 – 93%

Clinical Significance of an AGC PapClinical Significance of an AGC Pap

Source: Richart et al. Contemp Ob Gyn. 2001; 46:15-17,25-28,30-32,35-43.

Management of AGCManagement of AGC

Management of LSIL: Special CircumstancesManagement of LSIL: Special Circumstances

• Mod: Abnormal Pap-fig 6Mod: Abnormal Pap-fig 6

Management of HSILManagement of HSIL

• Mod: Abnormal Pap-fig 8Mod: Abnormal Pap-fig 8

Candidates for Ablative Candidates for Ablative or Excisional Therapyor Excisional Therapy

Patients who are suitable for ablative therapy have:

• The entire transformation zone visualized (satisfactory colposcopy)•   No suggestion of microinvasive or invasive disease•   No suspicion of glandular disease•    Corresponding cytology and histology

Patients in whom excisional treatment is mandatory have:

•         Unsatisfactory colposcopy•         Suspicion of invasion or glandular abnormality

Excisional TechniquesExcisional Techniques

Conization• A cone of tissue is excised for further examination and/or to remove a lesion• The tissue is usually stained with iodine (Lugol’s or Schiller’s solution) to

demarcate the area of resection

– Cold Knife Cone• The use of a scalpel or “cold knife cone” since no electrosurgical current

is used

– Laser Conization• The use of a laser for excision of a cone of tissue• May be complicated by burn artifacts

 – LEEP (Loop Electrosurgical Excision Procedure)

• The use of a thin electric wire loop, which may have cutting and cautery currents

• Different sizes of loop and cautery tip available• May be complicated by burn artifacts

Ablative TechniquesAblative Techniques

Cryotherapy• The use of a probe containing carbon dioxide or nitrous oxide to

freeze the entire transformation zone and area of the lesion• Different sizes of probe available

Laser Vaporization Therapy• The use of a laser to vaporize the transformation zone containing

the lesion• Requires suction to remove smoke • Different power levels are available

Cervical Cancer: FIGO NomenclatureCervical Cancer: FIGO Nomenclature

Stage 0:Stage 0: Carcinoma Carcinoma in situin situ, cervical intraepithelial neoplasia Grade III, cervical intraepithelial neoplasia Grade III

Stage I:Stage I: The carcinoma is strictly confined to the cervix (extension to The carcinoma is strictly confined to the cervix (extension to the corpus would be disregarded). the corpus would be disregarded).

Stage II: Stage II: Cervical carcinoma invades beyond the uterus, but not to Cervical carcinoma invades beyond the uterus, but not to the pelvic wall or lower third of the vagina. the pelvic wall or lower third of the vagina.

Stage III:Stage III: The carcinoma has extended to the pelvic wall. On rectal The carcinoma has extended to the pelvic wall. On rectal examination, there is no cancer-free space between the examination, there is no cancer-free space between the tumor tumor and the pelvic wall. The tumor involves the lower and the pelvic wall. The tumor involves the lower third of the third of the vagina. All cases with hydronephrosis or non-vagina. All cases with hydronephrosis or non- functioning functioning kidney are included, unless they are kidney are included, unless they are known to known to be due be due to other causes. to other causes.

Stage IV:Stage IV: The carcinoma has extended beyond the true pelvis, or has The carcinoma has extended beyond the true pelvis, or has involved (biopsy-proven) the mucosa of the bladder or involved (biopsy-proven) the mucosa of the bladder or rectum. A bullous oedema, as such, does not permit a case rectum. A bullous oedema, as such, does not permit a case to be to be allotted to Stage IV.allotted to Stage IV.

Stage I 82% 85% 76 – 90%

Stage II 61% 66% 50 – 70%

Stage III 37% 39% 30 – 35%

Stage IV 12% 11% 10 – 15%

FIGO Stage 5-Year 5-Year Recurrence Treatment Survival Treatment Survival (Einhorn3)

(Morrow et al1) (FIGO reports – Benedet2)

Cervical Cancer: Outcomes by FIGO Cervical Cancer: Outcomes by FIGO StageStage

1. Morrow CP et al. In: Morrow CP, Curtin JP (eds). Synopsis of Gynecologic Oncology, 5th ed. 1998. 2. Benedet JL. Int J Gynecol Obstet. 2000;70(1):135-147.3. Einhorn N. Acta Oncol. 1996;35(2Suppl7):75-80.

Cervical Screening SummaryCervical Screening Summary

• HPV is common and present in almost all cervical HPV is common and present in almost all cervical cancerscancers

• New screening technologies, specifically ThinPrep, New screening technologies, specifically ThinPrep, provide an increase in detection of LSIL, HSIL, an provide an increase in detection of LSIL, HSIL, an improved specimen, and reflex HPV testing improved specimen, and reflex HPV testing

• New Bethesda nomenclature plus the New Bethesda nomenclature plus the results of the results of the ALTS trial spurred new guidelines which provide an ALTS trial spurred new guidelines which provide an evidence-based approach to managing the evidence-based approach to managing the problematic ASC-US Pap resultproblematic ASC-US Pap result

• Reflex HPV testing is an efficient way to manage the Reflex HPV testing is an efficient way to manage the ASC-US Pap test result, specifying who is at risk and ASC-US Pap test result, specifying who is at risk and in need of immediate colposcopyin need of immediate colposcopy

Additional InformationAdditional Information

For a complete review of terminology and For a complete review of terminology and guidelines, go to:guidelines, go to:

Bethesda 2001:Bethesda 2001: www.bethesda2001.cancer.govwww.bethesda2001.cancer.gov

ASCCP Consensus Guidelines:ASCCP Consensus Guidelines: www.www.asccpasccp.org.org

Solomon D, Davey D, Kurman R, et al, for the Forum Group Members and the Bethesda 2001 Workshop. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002;287:2114-2119.