WHAT'S NEW IN CERVICAL DYSPLASIA

Introduction

GOAL OF THIS PRESENTATION: Review the recent medical literature and information important to family physicians caring for women, and that relates to colposcopy and diseases of the cervix and lower genital tract.

• HOW DOES CIN TREATMENT AFFECT ARE PREGNANCIES?

• FERTILITY AND PREGNANCY OUTCOME AFTER CIN Treatment

Studies not controlling for smoking and low socioeconomic status are difficult to interpret, since both of these factors increase the risk for preterm and low-birth-weight deliveries Fertility prob. affected after tint by cerv. stenosis, loss of cervical mucus, and tubal dysfunction Effect on pregnancy outcome prob. related to cerv. incompetence or difficulty in cervical dilation.  Spitzer M. l Lower Gen Tract Dis, 1998; 2: 225.
 
• FERTILITY & PREG. OUTCOME AFTER COLD-KNIFE CONIZATION


No controlled studies of fertility Weber's review concluded that there is no lessened fertility following cold-knife conization. Some studies suggest incr. in preterm deliveries. Removal of cervical conn. tissue may produce
weakness / inability to support full-term preg. Some have recommended prophylactic cerclage after CKC, but studies do not show a benefit.     Spitzer M. J Lower Gen Tract Dis 1998; 4: 225.
 

• FERTILITY AND PREG. OUTCOME FOLLOWING CRYOTHERAPY

Weed studied 412 women after cryotherapy, concluded no difference in fertility. Uncontrolled studies of cryotherapy have not demonstrated incr. in pretetm delivery or increase in cesarean delivery.  Spitzer M. l Lower Gen Tract Dis 1998; 2: 225.
 
• FERTILITY AND PREG. OUTCOME  FOLLOWING LASER THERAPY


Largest controlled retrospective study by Spitzer concluded laser did not adversely affect fertility. Controlled studies examining pregnancy outcome have not demonstrated an increase in preterm deliveries or pregnancy complications.
Spitzer M. J Lower Gen Tract Dis 1998; 2:225.
 

• FERTILITY AND PREG. OUTCOME FOLLOWING LEEP


Absence of a negative effect on fertility has been noted in several controlled studies. Several controlled studies of pregnancy outcomes following LEEP have failed to note any difference in gestational age, birth weight, or cesarean deliveries.  Spitzer M. J Lower Gen Tract Dis 1998; 2: 225.
 

• WHAT IS THE OPTIMAL ORDER IN PERFORMING A PAP SMEAR? THE ORDER OF ENDOCERVICAL  AND ECTOCERVICAL SAMPLING


More smears obscured by blood when brush used (4.4%) compared to spatula fast (0.6%) Adequacy of smears was equal between groups No endocervical cells in 5.8% of brush-first group compared to 9.0% in spatula-fast group (p = 0.7) More SIL in the spatula-fast group (l 1% vs. 7%) CONCLUSION: quality of smear improved by using Ayre spatula first, followed by cytobrush.  Eisenberger D. Obstet Gynecol 1997; 90: 755.
 

• TREAT THE CERVIX TOPICALLY BEFORE COLPOSCOPY?  INEFFECTIVENESS OF TOPICAL BENZOCAINE SPRAY


36 patients evaluated with benzocaine spray or placebo spray before colposcopy.  Pain scores increased significantly after application of either spray; benzocaine conferred no befit when used to decrease pain or anxiety associated with colposcopy.  Clifton PA. I Fam Pract 1998; 46: 242.
 

• TOPICAL BENZOCAINE GEL BEFORE COLPOSCOPY


125 women received gel or placebo. Topical benzocaine gel was ineffective in reducing discomfort reported on bx or ECC.  Biopsy instrument sharpness appeared critically important in level of pain.  Discomfort with prior Paps or pelvic exams, or hx of dysparunea assoc. with greater pain.   Ferris DG. 1 Lower Gm Tract Dis 1 997: 1: 221.
 

• IS ONE CIN TREATMENT MORE EFFECTIVE THAN ANOTHER?  COMPARISON OF TREATMENT MODALITIES FOR CIN


Randomized clinical trial of cryotherapy, laser vaporization, and LEEP for CIN
No difference in complications, high success rates
Recurrence risk highest in women > 30 yrs, those with HPV types 16/18, and those with prior dis.
CONCLUSION: No significant difference in the success rates for the three treatments were seen in this population
Mitchell Ice. Obstet Gynecol 1998:92:737.

WHAT IS THE NATURAL HISTORY OF GENITAL HPV INFECTION?

• NATURAL HISTORY OF HPV AMONG N.J. COLLEGE WOMEN


608 women followed for three years 26% were HPV-positive at the start
Increased risk of HPV was associated with incr. no. of vaginal sex partners, younger age, high freq. of vaginal sex and alcohol consumption, and increased lifetime partners for woman's partner
Average annual incidence of HPV was 14% About 60% infected sometime during 3 yr period
Ho GYF. N Engl J Mod 1998; 338: 423.
 

• HPV: A TRANSIENT INFECTION


A woman was likely to lose her HPV infection if it was newly acquired
31% resolved HPV in the first 6 mos, 39°/. in 2nd, and only 11% in 3rd 6 mos
Adolescents and young women experience shortlived HPV infections, and the manifestations (LGSIL) often undergo spontaneous resolution
CONCLUSION: conterv. mgmt for LGSIL/HPV
Ho GYF. N Engl J Mod 1998; 338: 423.
 

• PERSISTENT HPV INFECTION


Infection with high-risk types and older age were risk factors for persistent infection
Persistent HPV infection may in turn increase the risk of the development and persistence of SIL
The association between persistent infection and multiple types of HPV suggests women with deficient immune responses are more likely to develop a persistent infection
Ho GYF. N Engl 1 Mod 1998; 338: 423.
 

• PERSISTENT HPV INFECTION AND SIL


Relation between SIL and certain types of continuous HPV infections
Some types of HPV produce multiple episodes of SIL
Either continuous or episodic HPV increases the chance of catching SIL on periodic Pap smear
Ho GYF. N Ease l Mod 1998; 338: 423.
 

WHAT IS THE VALUE OF THE NEW HYBRID CAPTURE II TEST?

• HYBRID CAPTURE TECHNIQUE

Simple technique performed in a single day. Technique involves nucleic acid hybridization of HPV DNA which is recognized by antibodies and chemiluminescent reaction. The brush or broom have yielded better results, with higher yield of cells and median viral load than the brush. Swab may have merit in self-sampling screening
Cox JT. J Lower Gen Tract Dis 1999; 3 (suppl 1): S8.
 
• HYBRID CAPTURE II

Sens. appears 90%-100% in detecting dyspl. Hybrid capture I had a sensitivity of only about 80% - similar to a Pap smear Hybrid capture II may be relied upon to detect most high-grade SILs and cancers Possible FU of equivocal Paps (ASCUS) Should be FDA approved in 1999
Cox JT. 1 Lower Gen Tract Dis 1999; 3 (suppl 1): S8.
 
• HYBRID CAPTURE II IN PRIMARY SCREENING OF WOMEN > 35 YRS

Study performed on 3000 women > age 35
Sensitivity of cytology for HGSIL was 76%
Hybrid Capture II had a sensitivity of 89% for any HGSIL and 100% for CIN or a more severe pathology
CONCLUSION: HC II detected many cases of high-grade disease missed by Pap Quick J.
[Abstract] 1 Lower Gen Tract Dis 1999; 3:34.
 
• THINPREP PAP SYSTEM


Pap smears of 7360 women evaluated
65% more diagnoses of HGSIL or greater abnormality seen with ThinPrep compared to conventional smears
Greater number of adequate smears and fewer "adequate but limited by" smears with the ThinPrep
Lee KR. Obstet Gynecol 199 90: 278.
 

• REASONS WHY ALL FUTURE PAP SMEARS MAY BE THINPREP


ThinPrep identifies more histological dis. Individuals who read slides for a living prefer ThinPrep over dry slides
The residual cells in the vial can serve as a source for HPV testing , and in the future additional testing may be available as our technology and understanding increase.
Cox JT. J Lower Gen Tract Dis 1999; 3(suppl 1): S8.
 

WHAT SHOULD I KNOW ABOUT AUTOMATED PAP SCREENING?

• THE AUTOPAP SYSTEM

AutoPap device classifies ea. object on slide
Chooses slides examined microscopically
FDA recently approved the AutoPap as a primary screener at a 25% sort rate (25% archived, 75% screened manually)
FDA approval for qual.-control rescreening or 1° screening of conventional Paps only
Cox JT. J Lower Gen Tract Dis 1999; 3(suppl 1): S8.
 
• AUTOPAP "ENRICHING


CLIA req. 10% rescreening of nl smears
Automation incr. possibility of detecting >10% of missed cases if sample enriched
Using AutoPap increases 8X missed HGSIL
Cost is a consideration; automation incr. cost per case discov. from $1000 for 100% or selected rescreening to >$3000
Cox YT. J Lower Gen Tract Dis 1999; 3(suppl 1): S8.
 

• PAPNET SYSTEM


Gone.....
 

• THINPREP PAP SYSTEM


Pap smears of 7360 women evaluated
65% more diagnoses of HGSIL or greater abnormality seen with ThinPrep compared to conventional smears
Greater number of adequate smears and fewer "adequate but limited by" smears with the ThinPrep
Lee KR. Obstet Gynecol 199 90: 278.
 

• REASONS WHY ALL FUTURE PAP SMEARS MAY BE THINPREP


ThinPrep identifies more histological dis.
Individuals who read slides for a living prefer ThinPrep over dry slides
The residual cells in the vial can serve as a source for HPV testing , and in the future additional testing may be available as our technology and understanding increase
Cox JT. J Lower Gen Tract Dis 1999; 3(suppl 1): S8.
 

HOW IMPORTANT IS THE PAP FOLLOW-UP REPORTING SYSTEM?

• ASCCP GUIDELINES: PAP FOLLOW-UP


"The most difficult aspect of devising an optimum cervical cytological screening service for women is ensuring that patients will not "fall through the cracks" either in terms of notification of the abnomlal findings or in terms of subsequent followup "
Cox TJ. J Lower Gen Tract Dis 1997; 1: 167.
 

• ASCCP GUIDELINES: PAP FOLLOW-UP


"The most dangerous system is one in which the patient expects that her Pap smear or biopsy results are normal if she has not been notified otherwise."
Cox JT. J Lower Gen Tract Dis 1997; 1: 167.
 

• ASCCP GUIDELINES: GOOD PAP  SMEAR FOLLOW-UP SYSTEMS


Process by which the patient is assured of receiving notification of an abnormal Pap
Recall system that ensures patient returns
A set of guidelines that may be used by the clinician to ensure that uniform education & advice are presented to the patient
COX JT. J Lower Gen Tract Dis 1997; 1: 167.
 

WHAT GUIDELINES EXIST REGARDING PERFORMANCE OF  THE ECC?

• ENDOCERVICAL CURETTAGE

ECC is traditionally included in U.S. colposcopic exams, even when the SO and complete limits of a lesion are seen
Townsend concluded that the most common pretreatment colposcopy errors were failure to perform routine ECC and inadequate no. of bx
Recent reports fail to establish that routine ECC decreases occult invasive disease
Cox Yr. J coma Gen Tract Dis 1997; 1: 251.
 
• ECC ERRORS


Several reports describe poor ECC sensitivity at detecting neoplasia
Positive ECC in woman with a satisfactory exam and normal-appearing endocervical canal is likely to be a false-positive result
False+ ECC occurs when the endocervical curette "nicks" a lesion near the external os Cox JT. J Lower Gen Tract Dis 1997; 1: 25 1 .
 

• ASCCP GUIDELINE: ROUTINE ECC WITH EVERY COLPOSCOPY


"In the presence of a satisfactory colposcopy and a visually normal endocervical canal, data argue against performing routine ECC. Because of cost-effectiveness, less patient discomfort, and a lesser chance of subjecting women to unnecessary conization following false+ ECCs, the ASCCP recommends that ECC not be performed when colposcopy is satisfactory."

Cox JT. J Lower Gen Tract Dis 1999; 1: 251.
 

• ASCCP GUIDELINE: ECC AT  UNSATISFACTORY COLPOSCOPY


ASCCP recommends either ECC on all patients or on selected individuals
For LGSIL on Pap, ECC can be performed selectively when colposcopy unsatisfactory
For HGSIL on Pap, cone bx or electrosurgical loop excision is recommended when colposcopy unsatisfactory
Cox JT. J Lower Gen Trod Dis 1997; 1: 251.
 

• COST SAVINGS FOR SELECTED  ECC AT COLPOSCOPY


"Selective, rather than routine, endocervical evaluation by standard ECC or brush should reduce the costs of colposcopy and biopsy by $24-$ 100 per case for between 38°/.-81 of women evaluated. Savings should be greater for younger populations where most colposcopy will be adequate."
Cox IT. J Lower Gen Tract Dis 1997; 1: 251.
 

• DANGERS OF SELECTED ECC AT UNSATISFACTORY COLPOSCOPY


High false-negative rate makes this a poor final arbiter in unsatisfactory colposcopies Conization suggests ECC does not detect 50% of CIN III in canal and 37% of cancer Cone bx is necessary to evaluate all CIN on Pap with unsatisfactory colposcopy, and some argue ECC adds little to the work-up
Cox JT. J Lower Gen Tract Dis 1997; l: 251.
 

• CONSIDER ECC FOR SPECIAL SITUATIONS


Prior therapy may cause "skip" lesions in the endocervical canal; consider ECC for all patients with prior treatment to the cervix, even if satisfactory colposcopic examination present Women with glandular atypia or dysplasia on Pap smear also require ECC at colposcopy Novice colposcopists should perform routine ECC until experienced in assessing the SO and 7Z
Cox JT. J Lower Gen Tract Dis 1997;1: 251.
 

CAN THE ENDOCERVICAL BRUSH SUBSTITUTE FOR ENDOCERVICAL CURETTAGE?

• ASCCP GUIDELINE: ENDOCERVICAL BRUSHING


Brush is rotated m the canal 180 degrees to limit bleeding and to increase specimen adequacy
Alternately, brush can be gently rotated in the canal 5-10 turns with light pressure against walls
Immediately following brush withdrawl, material is applied to the slide and fixed
Alternately, brush can be cut from the shaft and placed in formalin
Cox Yr. J Lower Gen Toad Dis 1997; 1: 251.
 

• ASCCP GUIDELINE: ENDOCERVICAL BRUSH VS. CURETTE


Increased sensitivity of the brush may make it the preferred instrument for endocervical sampling False+ from brush are likely from contamination from passing over lesions at or near the cervical os Other brush false positives from brush effect of cell distortion or cell clumping Many authors suggest brush be the initial screen, followed by more specific ECC if brush is positive
Cox JT. J Lower Gen Tract Dis 1997; 1: 251.
 

• BRUSH TECHNIQUE THAT LIMITS  FALSE POSITIVE RESULTS


Slide sheath (straw) over the brush Place distal tip of straw 1.5-2.0 cm into the canal
Pull the straw back to uncover the brush Rotate the brush 1/2 turn (180 degees)
Slide the straw over the brush prior to withdrawl
Immediately fix the specimen on the slide
Notify pathologist brush sample not from screening. Pap)
Lower Gen Tract Dis 1 997; 1: 251.