A Novel Collection Device for Cervical Cytology

History of the Pap Smear

New cancer cases in the U.S. 2009 Estimates (Females):

Breast 192,370Uterus (womb) 42,160Ovary 21,550Cervix 11,270Vulva 4,000

Source: American Cancer Society, Cancer Facts and Figures 2009

How common is cervical cancer?500,000 women worldwide die of cervical

cancer annually60-65 million women in the U.S. have a

Pap test each year3-5 million women in the U.S. have an

abnormal result11,270 new cervical cancers diagnosed in

the U.S. in 20094,100 deaths from cervical cancer in the

U.S. per yearMost cervical cancer can be prevented

Pap SmearsConventional Liquid based monolayer (e.g.. Thin Prep)Spatula, Brush or Broom CollectionHPV testingAutomated Analysis

ClassificationBethesda System

Based on the probability of invasive cancer

Originally developed in 1998System revised in 2001Is the international gold standard for

classifying Pap specimens

Bethesda Classification (2001)Squamous Cell

Atypical squamous cells (ASC)Undetermined Significance (ASC-US)Not exclude High Grade (ASC-H)

Low Grade Squamous Intraepithelial lesion (LSIL) High Grade Squamous Intraepithelial lesion

(HSIL) Squamous Cell Carcinoma

Glandular Cell Atypical Glandular cells (AG)

Undetermined Significance (AG-US)Favors Neoplasm

Adenocarcinoma In Situ (AIS) Adenocarcinoma

Screening Guidelines for the Early Detection of Cervical Cancer

•Begin approximately 3 years after a women begins having vaginal intercourse, but no later than 21 years of age•Annually with regular Pap tests or every two years using liquid-based tests•At or after age 30: three normal test results in a row, screen every 2-3 years with cervical cytology alone(either conventional or liquid-based Pap test), or every 3 years with HPV DNA test plus cervical cytology•Women 70 and older who have had 3 or more consecutive Pap tests in the last 10 years may choose to stop cervical cancer screening•Screening not necessary after total hysterectomy (with cervix removal) unless done as a treatment for cervical cancer

American Cancer Society

Pap Test Abnormalities

60-65 million women screened

Cervical Cancer Detection and Treatment$7.6 billion Annual Expenditures in the United States

Approx. 65 million Pap Tests done in the US annually

Sources of Errors with Conventional Pap

Sampling errorsCells not collected on sampling deviceCollected cells not transferred to slideCells poorly preserved

Screening errorsCytologist misses abnormal cellsIncorrect classification of cells

*These errors all contribute to false negative results, with reported estimates ranging from 6-50%

SoftPAP® : A New Generation of Cervical Cell Collection

One-step collection of complete 360° sample

Collects both endocervical and ectocervical cells simultaneously

Less invasive and less traumatic specimen collection

Improved accuracy

SoftPAP® : Advantages over Conventional Methods

Statistically significant improvements vs. standard Spatula/Cytobrush

Improved sensitivityReduces false negatives by 26%

Improved specificityReduction of false positives of 33%

Ease of use for the provider

Greater patient comfort

Comparison of the Adequacy and Efficacy of SoftPAP® to Standard Specimen Collection for Cervical CytologyTrial Objective To demonstrate

equivalency of cervical cytology sampling using SoftPAP to conventional spatula/brush for cervical CA screening (Pap, HPV testing)

Patient Population 703 colposcopy clinic patients

Methods Randomized collection of cervical cytology specimens (compared for Pap, HPV testing)

Study Endpoints •specimen adequacy•sensitivity •specificity

SoftPAP® Results: Specimen Adequacy

SoftPAP® Results : Efficacy

* p <0.001

HPV vs. Cytology CorrelationSpatula/Brush

SoftPAP® Total

NHPV NEG

HPV POS N

HPV NEG

HPV POS N

HPV NEG

HPV POS

WNL1

53 66% 34% 58 67.2%

32.8%

111

66.7%

33.3%

ASC-

LSIL2

173

32.4%

67.6%

136

28.7%

71.3%

309

30.7%

69.3%

HSIL-

CA3

68 2.9% 97.1%

43 0% 100%

111

1.8% 98.2%

1 Within Normal Limits 2 Includes ASCUS, ASC-H, AGUS and LSIL3 Includes HSIL, CIS and Cancer

SoftPAP® Study Conclusions

Pinkerton, Guido, Ackerman, et al. Int J Obstet Gynecol, submitted 2009