Policy Statement

CLINICAL

P RAe

ICE

ELI

ES

POLICY STATEMENT* MANAGEMENT OF THE ABNORMAL PAPANICOLAOU SMEAR No. 70, January 1998

These guidelines have been prepared by the SOGC/GOC/SCC Policy and Practice Guidelines Committee and approved by Council. women in 1990. Similarly, there has been a reduction in the age- standardized rate of death from invasive cervical carcinoma from 7.4 per 100,000 in 1969 to 2.4 per 100,000 women in 1990. l Since the mid-1970s, however, the rate of decline in incidence and mortality has not decreased appreciably. In 1997, it is estimated that there will be 1,350 new cases and 390 deaths from cervical cancer. l Almost half of these newly diagnosed cases of invasive carcinoma fall into the category of "no cytology or cytology longer than five years ago."z (Current cervical screening strategies are opportunistic and depend upon physician and patient education for entry into a screening programme. Programmes that encourage patient entry into a cervical screening programme and provide a recall system should be put into place to reach women who do not routinely present for a cervical smear). The Papanicoloau cervical smear has not markedly reduced the morbidity and mortality for other histological subtypes of cervical cancer including adenocarcinoma to the same degree as squamous carcinoma because of a relative lack of knowledge of defined pre-malignant precursors. There are an estimated more than four million cervical smears taken each year in Canada, of which approximately eight percent (over 325,000) are abnormaL The

SOGC/GOC/SCC POLICY AND PRACTICE GUIDELINE COMMITTEE MEMBERS

Pierre Drouin, MD, FRCSC Josee Dubuc-Lissoir, MD, FRCSC Thomas Ehlen, MD, FRCSC Prafull Ghatage, MD, FRCSC Mark Heywood, MD, FRCSC RobertJ. Lotocki, MD, FRCSC K. Joan Murphy, MD, FRCSC Marie Plante, MD, FRCSC, (Chair) R. Michael Shier, MD, FRCSC

Montreal, Que. Montreal, Que. Vancouver, BC St. John's, Nfld. Winnipeg, Man. Winnipeg, Man. Toronto, Onto Quebec, Que. North York, Ont.

Other contributors: Drs. Valerie Capstick, Mark Carey, Robert Grimshaw (previous Committee Members), Dr. Cecil Wright from SCC and Dr. A. Dennis DePetrillo from GOc.

The Papanicolaou cervical smear is an accepted screening test that can reduce the morbidity and mortality associated with squamous cell carcinoma. There has been a reduction in the incidence of cervical carcinoma from 21.6 per 100,000 women in 1969 to lOA per 100,000

* Policy Statements: this policy reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate amendments to these opinions. They should be well documented if modified at the local level. None of the contents may be reproduced in any form without prior written permission of SOGe.

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, , , practising physician is faced with varying opinions and recommendations about techniques for the collection of cervical cytology smears and the frequency of taking these smears. The terminology of both cytology and histology varies, and opinions differ about when to refer for colposcopy to obtain a histologic diagnosis.

or squamous dysplastic cells in the smear confirm that the transformation zone has been sampled at least in part. The presence of endocervical cells suggest that sampling has occurred above the squamo-columnar junction. Columnar cells in the presence of squamous cells suggest a high probability that the transformation zone has been sampled. When either ectocervival or endocervical sampling is done alone, squamous or endocervical cells will predominate, respectively. The predominance of either squamous or endocervical cells may obscure the presence of dysplastic cells.

THE TECHNIQUE FOR OBTAINING A CERVICAL CYTOLOGY SMEAR

In the presence of a necrotic, ulcerative or fungating lesion, a biopsy is necessary. Approximately 50 percent of patients with an invasive cancer have a negative smear because of its endocervical location or the presence of red blood cells, white blood cells or necrotic cells obscuring the presence of malignant cells. A major cause of a false-negative cervical cytology smear is failure of the physician to sample the transformation zone. The transformation zone is the region lying between the columnar epithelium and mature squamous epithelium where squamous dysplasia and carcinoma occur. Because this area is not clinically apparent, the optimal technique for sampling the region at risk involves taking a combined cervical cytology smear that obtains cells from both the endocervical canal and the ectocervix. The cervical spatula has been accepted clinically as the most effective tool for sampling the ectocervix. There is debate about the ideal method for sampling the endocervix. Is the cytobrush or a saline moistened cotton swab more effective? The cytobrush yields more endocervical cells. The use of the cotton swab is associated with more cellular distortion and trapping of cells; both of these effects can be reduced by moistening the cotton swab in saline before use. If the end-point to be achieved is the identification of biopsy-proven dysplasia, then there is no difference between the cytobrush or the moistened cotton swab. 3 The efficacy of other devices that sample the ectocervix and the endocervix simultaneously require evaluation. Samples from the ectocervix and the endocervix can be placed on the same slide. Immediate fixation avoids artifact caused by drying that can impair interpretation. Sampling should be postponed until after normal menses or treatment of an infective leukorrhoea. Cytologists continue to debate the criteria necessary to ensure that the transformation zone has been sampled. The presence of endocervical and/or squamous metaplastic cells is generally regarded as evidence of adequate sampling of the transformation zone. 4 Metaplastic cells

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FREQUENCY OF SCREENING

All three Canadian Task Forces have addressed frequency of screening within a group of other recommendations that include the development of an information system, quality control of cytology labs and an evaluation of the programme. I -1 The Society of Obstetricians and Gynaecologists of Canada, the Society of Canadian Colposcopists and the Society of Gynaecologic Oncologists of Canada support the position that annual cervical cytologic examinations should be continued until all the recommendations are adopted and in place. Without all the recommendations in place to provide the necessary safeguards, the recommendations for cytology frequency should not be taken out of context. Currently, some provinces are addressing a more organized approach that will permit less frequent screening in low risk groups and enhance the ability to reach unscreened high risk groups. TERMINOLOGY

Cytology laboratories across Canada, and even within regions, use a variety of different classifications for reporting cervical cytology. Although a classification attempts to compartmentalize abnormal cytology, cervical dysplasia is a continuum. Hence, there is difficulty with variations in the cytologic interpretation of a smear between different cytologists and even with the same interpreter. Most Canadian cervical cytology laboratories use cytology terminology from the 1982 Walton Report (Table 1). However, because of our close academic ties to the United States, increasing numbers of Canadian laboratories are beginning to use the 1991 Bethesda System (Table 2) . To ensure understanding of a cytology report, and as both systems have their proponents, the new guidelines of the Canadian Society of Cytology will state

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, , , TABLE 1 TABLE 1

that cytologic diagnoses should be made using a combination of the two. The continued use of the original Papanicoloau classification or modifications of this classification should be actively discouraged. There are major potential difficulties that the Bethesda System may create for physicians: 1. Atypical squamous cells of undetermined significance (ASCUS) is a difficult category to define and understand. The category considers these smears abnormal but definitely not pre-malignant and they cannot be classified as within normal limits or as benign cellular changes. Although ideal, categorizing ASCUS as either reactive or pre-malignant is frequently not possible. Although the Bethesda system attempts to standardize the reporting of ASCUS and low-grade squamous intra-epithelial lesion (LSIL), variations of cytology interpretation will persist because there are no distinct boundaries between them. Further, the prefix "atypical" suggests that the physician should refer the patient for colposcopy. 2. Low-grade squamous intra-epithelial lesion (LSIL) contains cells suggestive of mild dysplasia and cells suggestive of human papillomavirus infection.

THE CANADIAN SOCIETY OF CYTOLOGY CLASSIFICATION THE CANADIAN SOCIETY CERVICAL-VAGINAL OF CYTOLOGY CLASSIFICATION SYSTEM FOR REPORTING DIAG NOSES" SYSTEM FOR REPORTING CERVICAL-VAGINAL DIAGNOSES* Unsatisfactory Unsatisfactory Reason and Recommendations Reason and Recommendations No abnormal cells No abnormal cells Abnormal cells consistent with benign atypia (nonAbnormal cells consistent with benign atypia (nondysplastic) dysplastic) M etaplasia Metaplasia Inflammatory Inflammatory Trichomonas effect effect Trichomonas Yeast effect effect Yeast Viral effect effect Viral Radiation effect effect Radiation Others (specify) (specify) Others Abnormal cells consistent consistent with with dysplasia dysplasia Abnormal cells Mild dysplasia dysplasia Mild Moderate dysplasia dysplasia Moderate Severe dysplasia dysplasia Severe Abnormal consistent with with malignant malignant disease disease Abnormal cells consistent unspecified Type unspecified in situ situ squamous squamous carcinoma carcinoma Consistent with with in with invasive invasive carcinoma carcinoma Consistent with carcinoma Squamous carcinoma Consistent with with adenocarcinoma adenocarcinoma Abnormal cells not not specifically specifically categorized categorized comments) (see comments)

f"* Canadian Task Task Force on on Cervical Cervical Screening Screening Programmes: Programmes:Cervical Cervicalcancer cancer screening of the the 1982 1982 Canadian Canadian Task Task Force Force screenong programmes: programmes: summary summary of report (Walton Report 1982).5 1982).5

TABLE TABLE 22 BETHESDA SYSTEM SYSTEM THE 1991 BETHESDA I-Adequacy Epithelial cell cell abnormalities abnormalities Adequacy of ofthe the specimen specimen Epithelial Satisfactory Squamous cell cell Satisfactory for for evaluation evaluation Squamous Satisfactory Satisfactory for for evaluation evaluation but but limited by ... (specify reason) Atypical cells cells of of undetermined undetermined significance: significance: Atypical Unsatisfactory Unsatisfactory for for evaluation evaluation...(specify reason) Qualify" Qualify* General categorization categorization (optional) (optional) Low General Low grade grade squamous squamous intra-epithelial intra-epitheliallesion lesionencompassing: encompassing: Within normal normal limits limits Within HPV** HPV'" mild mild dysplasia/CtN dysplasia/CiN II Benign cellular cellular changes: changes: see see desciptive diagnOSIs diagnosis Benign High High grade grade squamous squamous intra-epithelial intra-epitheliallesion lesionencompassing: encompassing: Epithelial cell cell abnormality: abnormality: see descriptive descriptive diagnosis Epithelial Moderate Moderate and and severe severe dysplasia, dysplasia. CIS/CiN CIS/CIN22and andCIN CIN33 Descriptive diagnosis diagnosis Squamous Descriptive Squamous cell cell carcinoma carcinoma Benign cellular cellular changes changes Benign Glandular Glandular cell cell Infection Infection endometrial cells, Endometrial cells. cytologically cytologically benign, benign. ininaapost-menopausal post-menopausal Trichomonas vaginalis Trichomonas vaginalis woman woman Fungal organisms morphologically consistent with Candida spp Fungal organisms morphologically consistent with Candida spp Atypical of coccobacilli coccobacilli consistent consistent with with shift Predominance of ofundetermined undeterminedsignificance: significance: Atypical glandular glandular cells cells of shift in in vaginal vagi nal flora flora Predominance Qualify* Bacteria morphologically consistent with Actinomyces spp Qualify" Bacteria morphologically consistent with Actinomyces spp Endocervical Cellular changes changes associated associated with with Herpes Herpes simplex simplex virus Endocervical adenocarcinoma adenocarcinoma Cellular virus Endometrial Other Endometrial adenocarcinoma adenocarcinoma Other Extra-uterine Reactive changes changes Extra-uterine adenocarcinoma adenocarcinoma Reactive Adenocarcinoma, Reactive cellular cellular changes changes associated associated with: with: Adenocarcinoma. NOS NOS Reactive Other Inflammation (includes (includes typical typical repair) repair) Other malignant malignant neoplasms: neoplasms: specify specify Inflammation Atrophy with inflammation ("atrophic vaginitis") Hormonal to vaginal vaginal smears smearsonly) only) Atrophy with inflammation ("atrophic vaginitis") Hormonal evaluation evaluation (applies (appliesto Radiation Hormonal Radiation Hormonal pattern pattern compatible compatiblewith withage ageand andhistory history Intra-uterine contraceptive device (IUD) Hormonal Intra-uterine contraceptive device (IUD) Hormonal pattern pattern incompatible incompatible with w ithage ageand andhistory: history: Other Hormonal Other Hormonal evaluation evaluation not not possible possible due dueto: to:specify specify

- * -----------------------------'------- - - - - - --J Atypical squamous or glandular cells of undetermined significance should be further qualified as to whether a reactive of a premalignant/malignant • Atypical squamous or glandular cells of undetermined Significance should be further qualified as to whether a reactive of a premalignant/malignant processisisfavoured favoured.. process Cellularchanges changesof of human human papillomavirus papillomaviru5 (HPV)-previously (HPV)-previously termed •••• Cellular termed koilocytosis. koilocytosis. koilocytosis koilocytosis atypia, atypia. or or condylomatous condylomatousatypia-are atypia-areincluded includedininthe thecatecategoryof oflow-grade low-grade squamous squamous intra-epithelial intra-epithelial lesion. lesion. gory

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, , , Management of this group may place emphasis on viral technology to distinguish low, intermediate and high risk viral oncogenic subtypes to define oncogenic risk. The clinical value of this technology has not been defined to date. 3. High grade squamous intra-epithelial lesion (HSIL) intra-epitheliallesion contains cells suggestive of moderate atypia to severe atypia and to carcinoma in situ. This suggests that patients are at equal risk of developing a malignancy if left untreated. The Bethesda System has important advantages. It insists on defining the adequacy of the smear and requests that reasons for an unsatisfactory smear be stated. It allows for descriptive diagnoses that would occur with benign cellular changes due to infection or reactive changes that occur with atrophic vaginitis and radiation. radiation . Further, the Bethesda System includes potential abnormalities of glandular cells from the cervix, uterus and upper genital tract that may be the presentation of abnormalities of those sites. Although the classifications are defined, each classification straddles the boundaries of the other (Figure 1). It is incumbent upon the practising physician to communicate to the cytopathologist if confusion about terminology exists. Cytopathologists should not make recommendations for management of an abnormal smear unless they are completely aware of the patient's past history of cytology smears. Recommendations should be made by the patient's physician who has the patient's complete clinical history. The simultaneous use of dual cytology terminology should prevent confusion for those that are familiar with the terminology from the Walton Report and unfamiliar with the Bethesda System.

INDICATIONS FOR COLPOSCOPY

The Papanicolaou smear is a screening test with inherent false-negatives and false-positives. ColposcopyB involves a series of clinical steps used to evaluate the cervix of the patient with an abnormal smear. The goals of colposcopy are to identify the transformation zone, to deterposcopyare mine if it is normal or abnormal and to obtain a directed classified as biopsy. For the colposcopy examination to be classifted satisfactory, the entire squamocolumnar junction must be seen. If the colposcopy is satisfactory, a biopsy can be taken from the area with the most severe epithelial change. If the transformation zone is not completely seen, even with manipulation of the lower endocervical canal, the colposcopy examination is considered unsatisfactory. A colposcopic directed biopsy is logically not possible and cone biopsy is indicated. Whether or not a routine endocervical curettage (ECC) should be part of every colposcopy examination has been debated extensively. It has been recommended that the examiner document that the endocervical canal is negative prior to treatment with destructive methods. Endocervical curettage should always be omitted during pregnancy. Endocervical curettage can be omitted when cases of unsatisfactory colposcopy are managed by cone biopsy because the denuded epithelium can hamper histologic evaluation of the specimen. "NATU RAL HISTORY" 0 F PRECU RSO R LESIONS

Studies to assess the "natural history" of cervical intra-epithelial neoplasia are difficult to perform. Those studies that only use cytology smears to follow patients are flawed by the inherent problems of screening cervical cytology. Because screening cytology samples the cervix, histology does not always correlate. All colposcopy clinics see the discrepancy between the referring smear and the colposcopy-directed biopsy. As an example,9 in Table 3,26 of of47 4 7 (55.3%) patients presenting with a smear suggestive ofHPV changes had colposcopy-directed biopsies demonstrating atypia (6 of whom had moderate to severe atypia), seven (14.9%) had no abnormality or inflammation and 14 (29.8%) had HPV suggested on histologic examination. Similarly, in patients presenting with mild dysplasia, 15 of 41 (36.6%) had moderate atypia or greater, 11 (26.8%) had no histologic abnormality and 15 (36.6%) demonstrated mild atypia. Personal and inter-observer

FIG RE 1 FIGURE

COMPARISON COMPARISON OF OF CYTOLOGY CytOLOGY CLASSIFICATION CLA$SIFICATIO~':

SYSTEMS SYSTEMS

DYSPLASIA DYSPlASIA

CIN"

BETHESDA ': 'ojIvJTHIN NORMAL

NORMAL

I.

ABNORMALCELLS CELLSCONSlSl(NT CONSISTENT" ABNORMAL WtTHBE 8E~iO~AiYP!A (sp4ildfYn;":K't;lt~otic atypiaj--':(;" WITH N ATYPtA IJpK. fy KoiIocytQloC .~J

u~Hs

BENIGN CELLOLAA CHANGES INfEGl"ION(opeeffy) a'AGti,,",(,pecify) ATYPICAl SQUAMOUS tEUS Of OJ NQNN 5IG FlCANCE

Squamous: cell.bnormalit~s:

MILO DYSPl.ASIA

..MODERAtE-DySPLASIA OOE....T£ oY?LASIA SEVERE DYSPLASIA CARCINOMA IN SITU

CINI

J-

SQUAMOUS CEll CARC!NOMA

LOW GRADE SQIJ....OUS tNTlIA EPITHELIAL LfSI()N

CINII CIN II

CIN',III CINIII SO\JAMOUS CEU CARO~A

.. Cervicailntra-ephheltal Neoplasia

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, , , TABLE TABLE 33

RESULTS RESULTSOF OFCOLPOSCOPICALLY COLPOSCOPICALLY DIRECTED BIOPSIES AND CERVICAL CYTOLOGIC CYTOLOGIC EXAMINATION' EXAMINATION'

I-Cytology Cytology

Mild HPV Negative InflamInflam- HPV Mild - Moderate Severe CIS Negative mation Dysplasia Dysplasia Dysplasia mation Dysplasia

f--

HPV 1.1.HPV

Moderate 4.4.Moderate Severe 5.5.Severe

I

Inflammation 6.6.Inflammation

-

r--

14 14

11

22

33

22

44

55

15 15

12 12

2

11

11

2 2

5 5

---

33

--55

---

20 20

-

11

5

--

--

variability of cytology and histology interpretation occurs because boundaries between the various degrees of dysplasia are indistinct (Table 4).10 Those studies that assess "natural history" after coloscopy-directed biopsy are flawed by the biopsy's potential for being therapeutic by removing the lesion. In 555 patients followed with mild dysplasia, Naisell et al. 11 demonstrated regression to normal in 342 (62%) within 39 months, persistence in 124 (22%) and 89 (16%) progressed to a higher grade of dysplasia. Two patients who progressed to carcinoma did not attend for follow-up. Their carcinomas were diagnosed at 125 and 79 months. In a similar study with 894 patients with moderate dysplasia without biopsy, Naisell et al. ll demonstrated regression to normal in 50 percent within 78 months, persistent in 15 percent and progression in 35 percent. Two of three patients who progressed to carcinoma did not attend for follow-up. The third patient developed a micro-invasive carcinoma despite follow-up with yearly smears. Syrjanen et al.13 published a similar study of 528 patients (Table 5). As expected, regression occurred more frequently with mild dysplasia and progression occurred more frequently with more severe dysplasia. Ostor has summarized the data from several studies (Table 6).14 Risk of progression to invasive carcinoma was estimated for CIN I to be one percent, for CIN II five

2

CIN IIIIll-Severe Dysplasia-CIS Severe DysplasiaCIS CIN

8(6) 8 (6)

11

41 41 (33) (33)

-

99 (7) (7)

GUIDELINES FOR MANAGEMENT

-

TABLE 55 TABLE CLINICAL COURSE COURSE OF OF HUMAN HUMAN PAPILLOMAVIRUSCLINICAL CERVICAL INTRA-EPITHELIAL INTRA-EPITHELIAL NEOPLASIA NEOPLASIA LESIONS CERVICAL

f-

Clinical Clinical course course

Koiloonly Koilo only NCIN NCiN

CINI CINI

CINII

RegreSSion 180 180 (66.7%) (66.7%) 59 59 (55.7%) (55.7%) 36 36 (52.9%) Regression

HISTOLOGIC INTRA-OBSERVER INTRA-OBSERVER REPRODUCIBILITY HISTOLOGIC

>--

47 (38)

A Negative smear (no abnormal cells) should be repeated annually, 22 (2) 1 1 (2) 1 1 unless a regional cytology registry is in -- 9(7) 9 (7) place that provides the necessary safeguards defined within the National Workshop on Screening for Cervical Cancer. 7 With these safeguards in place, longer intervals between screening events could occur if cervical cytology is nonnal. There is no indication for screening colposcopy. Unsatisfactory smears cannot be interpreted either as nonnal or abnonnal. abnonnaL Numerous reasons include lack of evidence that the transformation zone has been sampled, leukocytes and/or red blood cells obscuring the field, improper fixation causing drying artifact and too few cells. After the patient is appropriately assessed and treated, the cervical cytology should be repeated. Abnormal cells consistent with benign atypia can be due to either infective or reactive changes. The specific aetiology should be treated. If the smear is also considered unsatisfactory, it should be repeated. Infections with human papillomavirus (HPV) are common. The lesions of most patients with viral atypia suggestive of human papillomavirus (koilocytotic atypia) regress spontaneously. Those with persistent HPV infections after six to twelve months have a high risk (49%) of developing a high grade intra-epitheliallesionl5 and should be evaluated by colposcopy.

TABLE 44 TABLE

Initial Initial read read - CIN II-Moderate Dysplasia CIN IIModerate Dysplasia

--

1

66

--

Atypia 2.2.Atypia Mild 3.3.Mild

-

11

No.(%)

percent and twelve percent for CIN IlL However, many of the patients III. with CIN III were treated immediately.

.

Subsequent read -

73 (27%) (27%) 73

29 (27.4%) (27.4%) 16 16 (23.5%) 29

Progression Progression

17 (6.3%) (6.3%) 17

15 (14.2%) (14.2%) 14 14 (20.6%) 15

Recurrence Recurrence

Mild 29% M ild Dysplasia or Negative

Total Total

00

270 270

(2.8%) 33 (2.8%) 106 106

2(2.9%) 2 (2.9%) 68

(14.3%) 6 (14 .3%) 2 (14.8%) (14 .8%) 29 (69%)

5(11.9%) 5 (11 .9%) 42

'- -papillomavirus r-Abbreviations: Abbreviations: NCIN. NCIN, human human papillomavirus lesion without without cervical lesion

4% Mild Dysplasia or Negative

Adapted by by Scully Scully RE. RE, (;"om from studies studies by by Ringstead Ringstead J et al. Acta Adapted Acta Pathol Microbiol Scand (A) (Al 1978;862731978;86:273-8. Bellina JH et al. South Med JJ 8. Belli na JH M ic ro b iol Scand 1982;75:6-8, Ismail SM SM et et al. al. Histopathology Histopathology 1990;16:371-6. :6·8. Ismail 1990;16:37 1-6. 1982;75

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Persistence Persistence

CIN CINIII III

intraepithelial neoplasia neoplasia. Intraeplthelial

Note: Course Course of of lesions lesions is is after after more more than than 70 months months (mean) (mean) prospecNote: tive follow· follow-up. tive up.

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, , , FIGURE FIGURE 22

TABLE TABLE 6

ALGORITHM FOR MANAGEMENT MANAGEMENT OF OF ASCUS ASCUS ALGORITHM FOR

NATURAL C IN : A CRITICAL C RITICAL REVIEW REVIEW NATURAL HISTORY OF CIN:

Papers Subjects Subjects Category Regress. Regress. Papers (N)) Cited (N Cited

17 17

4,504 4,504

CINI CIN I

12 12

2,247 2,247

CINII CIN II

21 21

767 767

I CINIII

CIN III

57% 57% 43% 43% 32% 32%

Persist. Persist . Prog. Prog. Prog. Prog. CINIII CINIII Inv. Inv.

32% 32% 35% 35% ?<56%'0 ?< 56%*

11% 11 % 22% 22%

--

ASCUS

.-

1% 1% 5% 5% 12%* 12%*

ASCUS Favouring Neoplasia

limit to to report report of Cytol Cytol. andlor Umi! and/or Bx. Bx alone. alone. Exdude Exclude cone cone and and destructive destructive Rx. Rx. 'limited FU FU in in some some series. 'limited series.

Human papillomavirus typing plays no clinical role at present, but is currently under investigation. Demonstration of a high-risk oncogenic potential HPV subtype is of limited value. 16 The presence of a high-risk subtype does not mean progression is a natural consequence. Atypical squamous cells of undertermined significance (ASCUS) management is controversial (Figure 2). Although some have advocated immediate colposcopy, the high frequency of spontaneous regression and the false negative rate do not support this recommendation. Repeating the smear would be appropriate in three to six months. This should be continued until at least three consecutive smears are negative, after which the patient can return to having annual cytologic examinations. If cytology continues to demonstrate ASCUS, then colposcopy should be performed. (Regional or provincial guidelines may be different.) Squamous epithelial cell abnormalities of any severity ideally should be evaluated with colposcopy to obtain a histology diagnosis (Figure 3). Cytology reports suggestive of moderate dysplasia, severe dysplasia, carcinoma in situ and squamous cell malignancy, require colposcopy assessment and directed biopsy if the colposcopy is satisfactory. Treatment for squamous atypia is facilitated by a number of out-patient techniques that yield good results with minimal morbidity. Where colposcopy is unsatisfactory, a cone biopsy is required. Treatment for an invasive lesion is dependent on the stage and the general health of the patient. The management of a smear suggestive of mild dysplasia is controversial. False negative rates are reasonably high; spontaneous regression is frequent; and there is a low probability that cancer is present. It is quite safe to repeat the smear in three to six months if the patient is comsmear~ are normal, annual pliant. If three consecutive smears follow-up may be instituted. If any of the repeat cytology is abnormal, then the patient should be evaluated with colposcopy. Immediate colposcopy is an option for

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IF ANY 3 NOTWNl

WNL WNl-- WITHIN WITHIN NORMAL NORMALLIMITS LI M ITS

FIGURE FIGURE 33

ALGORITHM OF THE THE ALGORITHM FOR FOR MANAGEMENT MANAGEMENT OF ABNORMAL SMEAR ABNORMAL SMEAR MODERATE SEVERE CIS (HGSll)

KOILIOCYTOSIS MilD DYSPLASIA (LGSll)

REPEAT q 3·6 Mths II

X3

I

IF ~ll WNl

I"

I'

II

I IF

~NY I;Ir.:-~ _ _---l

INOTWNl l]

ANNUAL CYTOlOGY

WNL - WITHIN WITHIN NORMAL NORMAL LIMITS LIMITS WNl

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COLPOSCOPE

II

~---=7-====-~IJI

BIOPSY and TREAT

, , , 3.

the non-compliant patient. (Regional or provincial guidelines may be different.) Glandular epithelial cell abnormality requires evaluation that is dependent upon the apparent origin of these cells. It may be difficult, however, for the cytopathologist to be able to be definite. El1idocervical glandular abnormality should be assessed initially by colposcopy and endocervical curettage, recognizing the limitations of the technique by the site of origin and lack of colposcopic criteria for diagnosis. Ultimately, cone biopsy may be required for diagnosis. Uterine glandular abnormality should be assessed initially by endometrial biopsy. An extra-uterine site of origin, however, should also be suspected.

4. 5.

6.

7.

8.

SUMMARY Cervical cytology and the management of these precursors of cervical carcinoma have been instrumental in decreasing the incidence of, and the mortality from, cervical carcinoma. If all the recommendations in the 1989 Report of a National Workshop on Screening for Cancer of the Cervix 7 were implemented, we should be able to decrease further the incidence of invasive cancer of the cervix. There would be a better utilization of cervical screening by including groups that are currently not presenting for cervical cancer screening and by avoiding over-screening and treating others. Regardless of appropriate implementation of screening techniques, invasive carcinoma will still develop in some individuals. TIle National Cancer Institute is sponsoring a study involving 7,000 patients in a multi-centre trial and addressing the management of ASCUSjLSIL. Volunteers will be randomized to receive either: 1) immediate colposcopy and biopsy; 2) follow-up cervical cytology every six months; or 3) HPV DNA testing. In the HPV arm of the trial, patients will have immediate colposcopy or follow-up smears. The goal of the study will be to compare cost effectiveness and efficacy of the three management protocols. J soc OBSTET GYNAECOL CAN 1998;20:57-64

9.

10.

11.

12.

13.

14.

15.

16.

REFERENCES 1. 2.

National Cancer Institute of Canada: Canadian Cancer Statistics, 1996. Toronto, Canada 1996:15. Anderson GH, Benedet JL, Le Riche JC, Matisic JP, Thompson JE. Invasive cancer of the cervix in British Columbia: a review of the demography and screening histories of 437 cases seen from 1985-1988. Obstet Gynecol 1992;80: 1-4.

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