leslie ablard, m.d.. incidence/prevalence 3 rd most common gyn cancer in developed world 11,270 new...
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Cervical Cancer Screening and HPV
Leslie Ablard, M.D.
Cervical CancerIncidence/Prevalence3rd most common GYN cancer in developed world
11,270 new cases in 20094,070 deaths in 2009
Most common GYN cancer in developing countries
500,000 new cases annually240,000 deaths annually
Signs & Symptoms
Abnormal Vaginal Bleeding
Postcoital Bleeding Vaginal Discharge (watery, mucoid,
purulent, malodorous)
Cervical CancerRisk FactorsEarly onset of sexual activityMultiple sexual partnersHigh-risk sexual partner History of sexually transmitted diseases Smoking (not adenocarcinoma)High parityImmunosuppressionLow socioeconomic statusProlonged use of oral contraceptivesHx of vaginal or vulvar cancer
Vast majority of cases are caused by persistent high risk HPV infection
Most common Histologies◦ Squamous Cell Carcinoma◦ Adenocarcinoma◦ Adenosquamous
Human Papillomavirus
Lifetime cumulative risk of acquiring HPV in sexually active persons = 80%
Spectrum of HPVCondyloma AcuminataCervical DysplasiaCervical Cancer
> 150 different types of the virus15 High Risk Types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82)
16, 18 > 70% all cervical cancers 6, 11 90% genital warts
HPV Vaccine – Gardasil ®Active against 16, 18, 6, 11
FDA approved in US for girls & boys ages 9-26
6.2 million new infections per year 20 million active infections (prevalence) 330,000 cases of CIN 2, 3 11, 400 cases of cervical cancer
LEEP/Cone doubles risk of PTL and IUGR
Human Papillomavirus
HPV 16, 18◦ Association with abnormal pap tests
Human Papillomavirus
PAP Rate 16 18 Total/yr
ASC 5.1% 13% 6% 581,000
LSIL 2.6% 24% 10% 530,000
HSIL 0.7% 61% 7% 285,100
External Genital Warts◦ 500,000-1,000,000 new cases per year◦ 240,000 initial office visits per year◦ 1% of sexually active US population between 18-
49 yrs old◦ 1/3 of all STI dollars annually
Human Papillomavirus
HPV associated cancer deaths
Human Papillomavirus
Site Total Cancers
AF (%) Attributable Cases
Cervix 11,150 100% 11,150
Penis 1,280 40% 512
Vulva/Vagina 5,630 40% 2,252
Anus 4,650 90% 4,185
Airway 24,540 26% 6,380
Total 47,250 12% 24,479
ACIP recommendations◦ Females with abnormal pap results or genital
warts should be given one of the two vaccines if they are in the indicated age group to prevent from types she has not been exposed to previously
HPV
Cervical cancer is one of the most preventable cancers
In the past 30 yrs, Pap test has reduced cervical cancer deaths by over 80%
New ACOG screening guidelines published in December 2009
ACOG Bulletin 109
Persistent infection with HPV is a prerequisite for the development of cervical cancer and its precursors◦ At least 80% of women acquire genital HPV
infection at some point in their lifetime◦ HPV most common in teenagers and women in
their early 20s, prevalence decreases with age◦ Most HPV infected women will not develop
significant cervical abnormalities
Natural History of Cervical CA
Most HPV infections become undetectable in an average of 8-24 months
Most CIN lesions resolve spontaneously in adolescents and young women
HPV in older women is more likely to reflect persistent infection acquired in the past
HPV type and persistence of infection are the most important determinants of progression
Natural History of Cervical CA
@ 48 months – 50% CIN 2,3 @ 60 months- 60% CIN 2,3 @ 1 yr- 60% clear 35% persistent 3% HGSIL
Clearance of HPV
New Recommendations:◦ Begin at age 21◦ Prior guidelines begin at age 21 or 3 yrs after
onset of intercourse Why the change?
◦ HPV infection and minor cytological abnormalities common in young women
◦ Most are cleared in 1-2 yrs◦ Cervical cancer is extremely uncommon less than
age 25
When should Pap screening Begin?
0.1% of cervical cancer occurs before age 21 yrs◦ British data suggests that those cancers that
occur aren’t detected through screening 1-2 cases/ 1,000,000 girls age 15-19 Audit of UK cervical cancers found no
benefit of screening women 20-24 yrs old
US ONLY COUNTRY TO DO ANNUAL PAPS
Invasive Cervical Cancer in Adolescents- SEER Registry
Treatment for lesions destined to resolve without therapy
Treatment for CIN (LEEP) increases risk of◦ Preterm Birth (OR 1.7)◦ LBW (OR 1.8)◦ PPROM (OR 2.7)
◦ DOUBLES RISK!!!
Consequences of Screening Adolescents
Every 2 yrs for women age 21-29 Every 3 yrs for women age 30 or greater
(after 3 consecutive negative paps or with concurrent neg HR HPV)
Exceptions to extended screening◦ HIV
Twice first yr, annually thereafter◦ Immunocompromised◦ DES exposed◦ History of CIN 2,3 or cancer
Annual screening for 20 yrs after initial post-treatment suvelliance
Frequency of Cervical Cytology Screening
Why change?◦ Supported by both empirical data and
mathematical modeling studies◦ 31,728 women age 30-64 yrs in National Breast
Cervical Cancer Early Detection Program◦ Rate of CIN decreased with increasing number of
sequential negative Paps◦ If 3 consecutive negative Pap tests, prevalence of
CIN 3 was 0.019% with no cases of cancer
Screening Interval
Age 65 or age 70 in women with 3 consecutive negative Paps and no abnormal Paps in the past 10 yrs
ACOG guidelines accept either USPSTF (65) or ACS (70) age cutoff
If screening is discontinued, risk factors should be reassessed during the annual examination
When to discontinue screening
Why the change?◦ In well screened older women with HSIL rates are
low and cervical cancer is rare◦ Most cases of cervical CA in US women older than
65 yrs are in inadequately screened women◦ Cervical cancer develops slowly and risk factors
decrease with age
When to discontinue screening
False-positive cytology due to vaginal atrophy◦ Additional procedures◦ Anxiety◦ Unnecessary expense
Difficulty in getting satisfactory samples◦ Vaginal atrophy◦ Cervical stenosis
Consequences of screening older women
Discontinue screening in women with no history of CIN 2,3
Most abnormal test results are falsely positive◦ In one study, only 1.1% had cytological
abnormalities, no VaIN 3 or cancer◦ Continued screening is not cost-effective, causes
anxiety, and leads to over treatment
◦ HAVE TO DOCUMENT NO CIN 2,3 ON PATH
Discontinue Screening Following Hysterectomy?
“Papanicolaou test” - 1941 Dr. Babes & Dr. Papanikolaou 80% decrease in rates of cervical cancer in developed
countries over last 30 yrs due to widespread screening
A sample cervix cells from transformation zone.
junction of endocervix and ectocervix Use of spatula +/- cytobrush, broom stick 2 types – conventional, liquid-based Send for cytologic interpretation
What is a Pap Smear?
Conventional smear◦ direct application of cells to a slide
Liquid Based smear◦ 90% of all Pap smears in US◦ Transfer cells to a liquid preservative. Liquid
processed in laboratory and transferred to a slide
How to perform a Pap smear…
Specimen Adequacy◦ Is the transformation zone present ??
Negative for intraepithelial lesion or malignancy (NIL,NILM, NIELM) Squamous Cell
Atypical squamous cells Undetermined Significance (ASC-US) Not exclude High Grade (ASC-H)
Low Grade Squamous Intraepithelial lesion (LSIL) – encompasses CIN I High Grade Squamous Intraepithelial lesion (HSIL) – encompasses CIN II & III Squamous Cell Carcinoma
Glandular Cell Atypical Glandular cells (AG)
Atypical Endocervical Cells Atypical Endometrial Cells Atypical Glandular Cells Not Otherwised Specified (AG-NOS) Favors Neoplasm
Adenocarinoma In Situ (AIS) Adenocarcinoma
Bethesda System (2001) Classification
ASC-US◦ Reflex HPV testing if age > 21
If positive for high risk HPV (HRHPV) Colposcopy If negative Repeat Pap and HPV in 1 year
◦Adolescents (<21) Repeat Pap/HPV in 12 months HGSIL at 12 months - Colpo If ASC or greater in 12 additional months (total 24 months)- Colpo
◦Pregnancy with HR HPV- acceptable to defer pap/colpo post partum
Management of Abnormal Paps
ASC-H◦ Refer to colposcopy◦ If CIN 2,3- treat◦ If no CIN 2,3
Cytology 6, 12 months OR HPV at 12 months ASCUS or greater or HPV + - Colpo
Management of Abnormal Paps
LSIL◦ Adolescents (<21) Repeat Pap in 12 months- If ASCUS
or greater total 24 months- Colpo
◦ Pregnancy- acceptable to defer pap/colpo post partum
◦ Everyone else Colposcopy Non pregnant and NO lesion – ECC Preferred Unsatisfactory -ECC Preferred Satisfactory with Lesion -ECC Acceptable
No CIN 2,3- Cytology at 6,12 months OR HPV at 12 mo ACUS or +HPV- Colpo
CIN 2,3- Treat per guidelines
Management of Abnormal Paps
HSIL◦ LEEP or Refer to colposcopy
No CIN 2,3◦ Unsatisfactory- Diagnostic Excisional Procedure
(LEEP)◦ Satisfactory
Colpo and cytology for 6 months x 1 yr Diagnostic Excisional Procedure (LEEP)
CIN 2,3◦ Treat per guidelines
Adolescents- Persists for 24 months- LEEP
Management of Abnormal Paps
Glandular Cells;◦Atypical Glandular Cells
Subtype: Atypical Endometrial Cells Endometrial biopsy (EMB), endometrial currettage (ECC)
If no endometrial pathology Colposcopy Rest of Subtypes (AGC-NOS, endocervical, favor
neoplasm) Colposcopy EMB if over 35 or at risk for Endometrial Cancer ECC HPV DNA testing
◦Adenocarcinoma in situ Colposcopy, EMB & ECC Diagnostic Excisional Procedure / Total Hysterectomy?
Management of Cervical Dysplasia
Prepare your patient Obtain informed consent and answer her
questions Assure her you will attempt to minimize pain
(often a consuming worry) Make sure to know the pregnancy status of your
patient Ibuprofen 800 mg may be offered prior to
procedure or the night before and morning of the procedure, although its efficacy is questionable
Basic Components of Colposcopy
Quickly examine the vulva for obvious condylomata or other lesions
Warm the speculum with water or water soluble lubricants and insert the speculum
Examine the cervix Is the cervix inflamed or infected-looking An active cervicitis confounds colposcopic detail Do cultures if necessary Repeat Pap only if this is critical information Even a correctly performed Pap smear may irritate the
cervix and often causes bleeding Gently blot (not wipe) away any excess mucous using normal saline
Look for leukoplakia and abnormal vessels
Basic Components of Colposcopy
Generously place 3-5% acetic acid on the cervix- (Acetowhite correlates with high nuclear density)
◦ Mild acetowhite epithelium < Intensely acetowhite ◦ No blood vessel pattern < Punctation < Mosaic ◦ Diffuse vague borders < Sharply demarcated borders ◦ Follows normal contours of the cervix < "humped up" ◦ Normal iodine reaction (dark) < Iodine-negative epithelium (yellow) ◦ Leukoplakia - usually a very good (condylomata) or a very bad sign ◦ Atypical vessels - a hallmark of cancer
Basic Components of Colposcopy
Nearly all cervical neoplasia occurs in the TZ◦ This is even true of the adenocarcinomas, which are often associated
with adjacent high-grade squamous disease
◦ This is because it is the reserve cells undergoing metaplasia that are vulnerable to various carcinogens such as HPV
◦ Metaplasia is at peak activity during adolescence and first pregnancy, it is understandable that early age on sexual activity and first pregnancy are known risk factors for cervical cancer
◦ Given a particular lesion, the more severe disease tends to be cephalad in the TZ, where the epithelium is least mature
◦ In order that a colposcopic exam may be deemed “satisfactory” or “adequate,” the TZ must be seen in its entirety, all the way up to the columnar epithelium, 360°, which means that all areas involved in squamous metaplasia have been visualized
◦
Transformation Zone
“Satisfactory” and “Adequate”◦ Entire TZ visualized◦ All lesions seen in their entirety
◦ Tools to help Endocervical Speculum Small Q-tip
If not-----ECC
Basic Components of Colposcopy
Stains Glycogen May be used by the beginning colposcopist or at any time when further
clarification of potential biopsy sites is necessary Iodine staining does not interfere with histology Lugol's solution is often very helpful on the vagina and proximal vulva
(non-keratinized skin) It can be used to thoroughly and simultaneously examine the entire vagina
for glycogen-deficient areas, which correlate with HPV and/or dysplasia in non-glandular mucosa
It is often reserved for difficult cases when a non-cervical source of cervical Pap smear atypism is suspected (as in "normal cervical colposcopy" with dysplasia on Pap smear or normal ECC histology)
Lugol’s or Schiller’s Test
Historically we have over-screened and over- treated women
ACOG 2009 guidelines are based on sound mathematical and epidemediologic data
HPV type and Persistence is the greatest predictor of the progression of dysplasia
Colposcopy beginners rule- Biopsy everybody
Summary
Thank You