Evolution of Cervical Cancer
Screening… and New Horizons
Richard W. Lieberman MD, FACOG, FCAP
Clinical Associate Professor, Obstetrics & Gynecology
and Anatomic Pathology
University of Michigan Medical School
Ann Arbor, Michigan, USA
Disclosures
• No financial relationships or conflict of interest to disclose
Invasive Cervical Carcinoma: the “typical”
presentation in the era before screening
3
Virchow
“Omnis cellula e cellula”
- every cell from a cell
Cellular Theory
© Humboldt-Universität zu Berlin, Universitätsbibliothek
4
Virchow Diagram of “canceroid” of
“the neck of the uterus”
• From 1858 Lectures on
“Cellular pathology as based
upon physiological and
pathological histology”
From “Cellular Pathology: 20 Lectures” Rudolf Virchow;
translated by Frank Chance, Lippincott & Co., 1863
5
Before the Screening Era of Cx CA:
Typical Clinical Presentation
Asymptomatic
Early
Late
Thin, watery, blood-tinged vaginal
discharge
Intermenstrual bleeding, postcoital spotting
Pain
 Dysuria, hematuria, obstipation
 Lower extremity edema
adapted from
Dr. Lori Boardman
…from the 8th Annual Meeting of the American
Gynecological Society (1883)
• mortality from cervical cancer
• “…91 patients treated
by hysterectomy to 1883
…66 died.”
• “Some of these achievements are
scarcely more than ante-mortem
examinations…”
–A. Reeves Jackson
From “Obstetrics and Gynecology in America: A HISTORY”
ACOG, 1980
7
January 1928: “New cancer diagnosis”
New cancer diagnosis.
Battle Creek, MI, January 2-6, 1928
8
January 1927
Romania refers to
cervical testing as
"Methode BabesPapanicolaou" in honor
of Dr. Babes.
Aurel Babes, 1886-1961
Dr. Naylor’s Collection
9
• 1941: landmark article
Dr. Naylor’s Collection
• 1949: widespread use of “PAP test”
10
PAP Collection Techniques: 1940’s-1990’s
1940’s Pap –Vaginal Pool Collection
Currently Accepted Method
11
“A Neoplastic Continuum?”
from Blaustein,
Fig. 7.14, 1987.
•maybe not
from Papanicolaou Monograph 1954
The B. Naylor Collection
13
PAP Smear Terminology: Historical Perspective:
1940’s-1980’s (1990’s…)
Class I
Class III
Class II
Inflam
CIN 1
Mild
Dysplasia
Moderate
Dysplasia
Koilocytosis
CIN II
Class IV
Carcinoma
In-situ
Severe
Dysplasia
Invasive
Carcinoma
Normal
Atypia
Class V
CIN III
CIN II
Meissels Acta Cytologica 20:505,1976
PAP Smear Nomenclature: Problems for years…
lack of standardization
• Class IA, Class II, Class IIA
• variable criteria
• regional, hospital, and individual!
• resulted in…
• poor predictive value
• equated with clinical confusion
• “who is really at risk for cervical cancer?”
did not address new information regarding the role of HPV infection,
high and low risk subtypes
then…
16
Age Adjusted Cancer Death Rate – Uterine Cervix
40
modified from American Cancer Society Statistics, 1992
Death Rate Per 100,000
35
30
25
United States
3rd World Countries
20
15
10
5
0
1930
1940
1950
1960
1970
1980
1990
Conventional PAP
ThinPrep Cytology
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1990’s: Liquid-Based Cytology
• Sample is collected in a
preservative solution
• automated cell retrieval with a
“thin” monolayer of cells
• fewer unsatisfactory smears
• additional testing (i.e. HPV-DNA)
19
Mid-1990’s: ALTS:
ASCUS — LSIL Triage Study
Three tiered prospective study of patients newly diagnosed with ASCUS or LSIL
ASCUS
•
HPV-DNA testing predicts outcome (pos = ~10% CIN2+)
LSIL:
•
•
changed to all colposcopy as 15 to 30% = CIN2+, and
>80% high risk HPV +
Leads to “reflex testing” for ASC-US, and ultimately co-testing for women over
30
The Last Quarter Century of Cervical Cancer Screening/Prevention
2012: L.A.S.T. and…
Updated Consensus Guidelines: Management of
Abnormal Cervical Cancer Screening Tests and Cancer Precursors
2006: ASCCP Algorithms for Guidelines (important refinements)
2001: TBS, second revision; FIRST Management Guideline (cyto and histo)
1996: ALTS (ascus-lsil triage study)
1991: TBS, initial revision
1988: The Bethesda System (TBS)
Increasing
knowledge
about
HPV
&
Cervical
Cancer
Risk
21
Cervical Cancer Screening, US
4,220 deaths
HSIL
LSIL
ASC
~12,170 new
Cancer
55 million
annual Paps
300,000
1,250,000
2,500,000
CA Cancer J Clin 2012 and SEER 2008
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System Failures Leading to Cervical Cancer Diagnosis
4. Patient does not get
appropriate therapy
Patient gets
cervical cancer
2. Health care providers
do not screen women
at visits
1. Women do not
come in for
screening
3. Colposcopy for
abnormal screen
not done
Modified from and Courtesy of Connie Trimble, MD, Johns Hopkins University School of Medicine,
Baltimore, MD
System Failures Leading to Cervical Cancer Diagnosis
4. Patient does not get
appropriate therapy
Patient gets
cervical cancer
2. Health care providers
do not screen women
at visits
1. Women do not
come in for
screening
3. Colposcopy for
abnormal screen
not done
Courtesy of Connie Trimble, MD, Johns Hopkins University School of Medicine, Baltimore, MD
System Failures Leading to Cervical Cancer Diagnosis
4. Patient does not get
appropriate therapy
2. Health care providers
do not screen women
at visits
6. Boys &Girls
do not
get HPV
vaccine!
Patient gets
cervical cancer
1. Women do not
come in for
screening
3. Colposcopy for
abnormal screen
not done
Courtesy of Connie Trimble, MD, Johns Hopkins University School of Medicine, Baltimore, MD
Lancet Glob Health 2016; 4: e453–63
26
Decline in in-patient treatments of genital warts among young Australians
following the national HPV vaccination program
Ali et al. BMC Infectious Diseases 2013, 13:140
27
Challenges for the future…
Educate about prevention:
goal: immunize every child prior to sexual debut
Make sure every woman is screened for cervical cancer
HOWEVER, EVEN “cost effective” screening and triage…
…is only effective if there is universal access to these essential services
…otherwise women will continue to die of a preventable disease
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