leslie ablard, m.d.. incidence/prevalence 3 rd most common gyn cancer in developed world 11,270 new...

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


HPV 16, 18◦ Association with abnormal pap tests


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


HPV associated cancer deaths


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


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


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


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


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


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


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

leslie ablard, m.d.. incidence/prevalence 3 rd most common gyn cancer in developed world 11,270 new...

Documents