Summary

Objective: To compare the AutoCyte^® PREP Thin-layer Pap Test with the conventional Pap test using the wooden Ayre spatula combined with Cytobrush in obtaining adequate cervical smears, by looking at the number of unsatisfactory and suboptimal smears obtained in cervical cancer screening in Elderly Health Centres (EHCs) using the two methods.

Design: Retrospective study on Pap tests performed in EHCs from January to September 2002.

Subjects: All Pap tests performed in the 18 EHCs during the study period.

Main outcome measures: The frequencies of unsatisfactory, suboptimal smears and the rate of detection of abnormal cytology.

Results: A total of 4,205 Pap tests were performed in the 18 EHCs with 1,795 thin-layer Papanicolaou tests and 2,410 conventional Pap tests done during that period. Of the 1,795 Autocyte prep specimens, 53 (3.0%) and 33 (1.8%) were unsatisfactory and suboptimal compared with 110 (4.6%) and 110 (4.6%) of the 2,410 conventional Pap smears: a reduction of 34.8% and 60.9% respectively. There was no significant difference in the detection rates of abnormal smears between the two groups.

Conclusion: Use of the liquid-based cytopreparation in elderly women aged 65 or above in Hong Kong has significantly reduced the unsatisfactory rate and suboptimal rate in cervical smears reporting. The improved quality improves diagnostic sensitivity of the test to detect cervical cancer.

Keywords: Thin-layer Pap test, cervical cancer screening, elderly

摘要

目的：以長者健康中心所做的柏氏抹片中不滿意和不理想抹片數目，比較薄層柏氏抹片和傳統柏氏抹片。子宮頸細胞抹片檢驗方法。

設計：回顧從二零零二年一月到九月於長者健康中心柏氏抹片結果。

對象：在研究期內所有十八間長者健康中心內進行的柏氏抹片測試。

測量內容：不滿意的和不理想的柏氏抹片以及發現問題細胞的抹片比率。

結果：研究期內十八間長者健康中心的柏氏抹片測試總數為4,205個。1,795測試為使用薄層柏氏抹片方法，2,410測試則為傳統的方法。利用薄層柏氏抹片方法中53塊(3.0%)和33塊(1.8%)分別被介定為不滿意的和不理想的柏氏抹片。相比較用傳統的子宮頸抹片方法，則分別為不滿意110塊(4.6%)和不理想110塊(4.6%)。薄層柏氏抹片技術令不滿意的和不理想的柏氏抹片比率分別降低了34.8%和60.9%。至於發現問題細胞的抹片比率則沒有明顯分別。

結論：香港六十五歲或以上的年長女仕中，使用液態細胞準備方法，能有效的減低被介定為不滿意和不理想的柏氏抹片報告比率。因為抹片質素的改善，子宮頸抹片測試的敏感度得以提升。

主要詞彙：薄層柏氏抹片，子宮頸細胞抹片檢驗，長者

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Introduction

Cervical cancer is the fourth most common cancer in women in Hong Kong with an age-standardized incidence rate of 9.8 per 100,000.¹ According to the age-specific incidence of invasive cervical cancer, there are two peaks in the local population, one at around age 45 to 55 and another at age 70-75.²

The National Institute of Health (NIH) has issued a statement proposing that women over age 65 should continue to be screened for cervical cancer. This is particularly true for women who have not received prior regular screening.³

However, the sensitivity and specificity of Pap (Papanicolaou) smear screening have always been important issues. False negative rates are of particular concern because there have serious consequences. A false-negative rate of up to 20% has been reported for the conventional Pap smear.^4,5 Recent studies have indicated that sampling errors may account for approximately 67% to 90% of false negative smears.⁵

In the elderly, obtaining an optimal Pap smear with adequate cellularity and cells from the transformation zone is known to be problematic because of the atrophic cervical os and the effects of oestrogen deficiency.

Liquid-based cytology is a new technology developed to improve the quality of cervical specimen preparation and hence the diagnostic sensitivity of the test. The sample is collected in the usual manner with a broom like sampler. Instead of being smeared directly onto glass slides, the material is rinsed into vials containing preservative fluid. The vials are then sent to the laboratory for further processing and preparation of uniform "thin-layered" slides for cytological interpretation. In principle, the liquid-based technique improves transfer of cells from the collection device, ensures uniformity of the cell prepared on the slide and minimizes obscuring effects by blood, mucus and inflammatory cells. These factors should improve the quality of the smears and decrease the number of unsatisfactory smears.⁶ However, there is no structured local study to evaluate this new technology as compared to the conventional method of obtaining Pap smears in the elderly population.

The Elderly Health Services in Hong Kong was established by the Department of Health in 1998 for the promotion of elders' health. By the year 2002, there were 18 elderly healthy centres (EHCs) providing health assessments, screening and health education for elderly persons aged 65 and above. All female elderly subjects were invited for Pap smear screening if they were not in another regular screening programme.

In the year 2002, seven elderly health centres were selected to adopt the AutoCyte^® PREP Thin-layer Pap Test (TriPath Imaging^TM, Inc.) as a pilot study, while the remaining 11 centres continued to use the conventional method for obtaining the Pap smear. The objective of this study is to compare the overall specimen adequacy in terms of the number of unsatisfactory and suboptimal smears obtained in cervical cancer screening in EHCs using the new technique versus the conventional Pap test with combined use of wooden Ayre spatula and Cytobrush.

Methods

In 2002, seven of the 18 EHCs were randomly selected to perform AutoCyte^® PREP Thin-layer Pap Tests while the others continued with conventional Pap tests. All conventional Pap smears were performed by the doctors of the EHC following the standard guidelines for obtaining optimal cervical smears, as set by the Department of Health. Doctors of EHCs selected for performing the new test were instructed about the collection method by both on-site and video demonstration. Broom-like samplers were used to collect specimens in the liquid-based method, while wooden Ayre spatulas combined with Cytobrushes were used for conventional Pap tests. In the new technique, the material on the collection devices was rinsed directly into the vials containing a methanol-based fixative and then

submitted to the laboratory for processing. In the conventional Pap test, the cellular material was smeared directly onto a glass slide and then sprayed with cytology fixative. The samples were then examined and reported by qualified cytotechnicians and cytopathologists in the Department of Health, using the Bethesda System 1991. The smear results were recorded and analyzed.

To test the null hypothesis that there was no difference in the two groups, the frequencies of unsatisfactory, suboptimal smears and the rate of detection of different abnormal cytology from January to September 2002 were compared retrospectively using the chi-square test with SPSS 11.0 as statistical software package (SPSS In., Chicago, IL, USA).

Results

A total of 4,205 Pap tests were performed in the 18 EHCs, with 1,795 thin-layer Papanicolaou tests and 2,410 conventional Pap tests done during that period. The demographic data of the two groups of elderly health centres were not significantly different (Table 1). Results were listed in Table 2.

Table 1: Comparison of demographic data of the two groups

Conventional   Monolayer   P-value     Mean   S.D.   Mean   S.D.       Age 72.94   5.53   73.2   15.57     0.27     %       %         Marital status                   0.329   Married   48.1       44.4           Widowed   47.1       49.9           Never married   2.8       2.9           Separated or divorced   2.0       2.9           Others   0.1       0                                 Smoking history                     0.112   Never-smoked   90.7       88.1           Ex-smoker   7.4       9.0           Current smoker   1.9       3.0                                   CSSA/Public assistance                     0.74   Yes   16.2       16.8           No   83.8       83.2                                 Old age allowance                     0.463   Yes   72.0       73.5           No   28.0       26.5                                 Major source of income                     0.801   Contribution from relatives   74.0       74.8           Public assistance   15.3       15.8           Savings   7.2       5.7           Pension   1.2       1.4           Salary   1.1       0.9           Others   0.8       0.9           Old age allowance   0.3       0.6                                   Monthly personal expenditure                     0.299   <$1,000   13.1       12.8           $1,000 - $1,999   41.1       41.7           $2,000 - $2,999   33.0       29.5           $3,000 - $5,999   11.7       14.6           $6,000 - $9,999   0.8       1.2           $10,000 or over   0.2       0.2                                   Family history of cervical cancer                     0.714   Yes, first degree relative   0.8       0.9           Yes, other relatives   0.1       0           No   99.1       99.1

Table 2: Comparison of thin-layer and conventional Pap tests

Conventional (N=2,410)   Thin-layer (N=1,795)       Total (N=4,205)     N %     N %     p-value   N %   Unsatisfactory   110 4.6     53 3.0     0.007   163 3.9   Suboptimal   110 4.6     33 1.8     <0.001   143 3.4   ASCUS∫   37 1.5     36 2.0     0.248   73 1.7   AGUS∮   0 0.0     0 0.0     N/A   0 0.0   SIL♀   0 0.0     0 0.0     N/A   0 0.0   LSIL⊕   9 0.3     6 0.2     0.833   15 0.2   HSIL※   8 0.3     10 0.6     0.269   18 0.4   Adenocarcinoma   0 0.0     1 0.1     0.427   1 <0.1   SCC☆   1 <0.1     0 0     1.000   1 <0.1   Positive (ASCUS or higher)   55 2.3     53 3.0     0.174   108 2.6     ASCUS∫   -   atypical squamous cells of undetermined significance AGUS∮   -   atypical glandular cells of undetermined significance SIL♀   -   squamous intraepithelial lesion LSIL⊕   -   low-grade squamous intraepithelial lesion HSIL※   -   high-grade squamous intraepithelial lesion SCC☆   -   squamous cell carcinoma

Of the 1,795 Autocyte prep specimens, 53 (3.0%) and 33 (1.8%) were unsatisfactory and suboptimal compared with 110 (4.6%) and 110 (4.6%) of the 2,410 conventional Pap smears: a reduction of 34.8% and 60.9% respectively. There was no significant difference in the detection rates of abnormal smears between the two groups. The overall positive detection rate for ASCUS or higher cytology was 2.6%.

There was one Pap smear reported as suspicious for endocervical adenocarcinoma and one reported as invasive squamous cell carcinoma. The former was from a 72-year-old lady who was then referred for biopsy, with the result showing adenocarcinoma in-situ. The latter was from a 68-year-old lady in whom biopsy samples confirmed the diagnosis of carcinoma of the cervix. Both underwent radiotherapy.

Discussion

Improved quality of cervical smear preparation improves the sensitivity of the test in the detection of cervical cancer. Poor sampling, uneven cell distribution or improper fixation of the material may hinder interpretation of the conventional Pap smear. Important findings may be obscured by uneven sample distribution, cellular clumping and debris. The liquid based cytopreparation is designed to reduce these problems. Most cancers and precancerous lesions arise in the transformation zone of the cervical canal. An adequate smear should sample the whole transformation zone with sufficient well preserved squamous cells. Atrophy of the cervical os, regression of the transformation zone and oestrogen deficiency make adequate sampling in the elderly difficult. Introduction of the combined Cytobrush with supervision and training in sampling in the EHCs has successfully reduced the unsatisfactory and suboptimal rate from 21.3% in 1999⁷ to 13.9% in 2000.⁸ In this study, the unsatisfactory and suboptimal rates were further significantly reduced from 9.2% in the conventional Pap test to 4.8% in the Autocyte Thin-layer Pap Test.

In a local study,⁹ the ThinPrep Pap Test, another liquid-based cytology technology, was also shown to be more effective than the conventional Pap test in detecting squamous intraepithelial lesions, although this study was not limited to the elderly population.

The major disadvantage of the thin-layer technology as compared to the conventional test is cost. In an Australian study, patients were levied an additional fee of about HK$100 if they requested a ThinPrep Pap smear. In the United States, the additional cost has been estimated to be about HK$78 each smear.¹⁰ In Hong Kong, the disposable plastic consumables are estimated to cost HK$20 more per test excluding the increased laboratory cost due to processing time. However, with the significantly better quality slides produced, the liquid-based preparation may reduce costs by reducing the number of patient visits for repeat smears. On the other hand, if we are to enhance the success of cervical cancer screening programmes, measures to ensure women's compliance with the programme and to improve access by the unscreened population are equally if not more important as improving sampling technique.

Conclusion

Use of the liquid-based cytopreparation in elderly women aged 65 or above in Hong Kong significantly reduced the unsatisfactory rate and suboptimal rate in reporting of cervical smears. The improved quality improves diagnostic sensitivity of the test in the detection of cervical cancer.

Key messages

1. Cervical cancer is the fourth most common cancer in women in Hong Kong. According to the age-specific incidence of invasive cervical cancer, there are two peaks in the local population, one at around age 45 to 55 and another at age 70-75. Women over age 65 should continue to be screened for cervical cancer. This is particularly true for women who have not received prior regular screening.
2. The false negative rate is of particular concern because it has serious consequences. False-negative rates of up to 20% have been reported for the conventional Pap smear. Sampling errors may account for approximately 67% to 90% of all the false negative smears.
3. In the elderly, obtaining an optimal Pap smear with adequate cellularity and cells from the transformation zone is known to be problematic because of the atrophic cervical os and the effects of oestrogen deficiency.
4. Liquid-based cytology is a new technology developed to improve the quality of cervical specimen preparation and hence the diagnostic sensitivity of the test.
5. Use of the liquid-based cytopreparation in elderly women aged 65 or above in Hong Kong significantly reduced the unsatisfactory rate and suboptimal rate in reporting of cervical smears. The improved quality improves the diagnostic sensitivity of the test in the detection of cervical cancer.

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References