Acta Cytologica 2020
Acta Cytologica 2020
aLaboratory
Medicine and Forensic Technology, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil;
bHospital
Naval Marcílio Dias, Pathology Service, Rio de Janeiro, Brazil; cFaculdade de Farmácia, Universidade
Federal do Rio de Janeiro, Rio de Janeiro, Brazil; dLipids Laboratory-LabLip, Faculty of Medical Sciences, Rio de
Janeiro State University (UERJ), Rio de Janeiro, Brazil
antonio-carlos.almeida @ marinha.mil.br
vention and early diagnosis are essential to reduce can- creased from 3% (conventional cytology) to 5.7% (LBC).
cer-related morbidity and mortality. In 2009, Beerman et al. [10] analyzed 86,469 gynecologi-
Cervical cancer screening has been primarily carried cal cytology records from a database, in which 51,154
out by conventional cytology. Several institutions are used conventional cytology and 35,315 used BD Sure-
continually evaluating the results obtained after the im- Path®. They observed a reduction in unsatisfactory sam-
plementation of liquid-based cytology (LBC). Tao et al. ples with the use of LBC (0.30% for LBC vs. 0.89% for
[4] compared 1,248,785 results from patients from an ac- conventional cytology). They also noted a higher detec-
ademic hospital in China between 2009 and 2014. The tion of cellular atypia when using LBC (2.97% for LBC vs.
samples were processed using LBC, either BD SurePath® 1.64% for conventional cytology).
or ThinPrep®, and conventional cytology. They observed Simonsen et al. [11] studied 2 devices (Cervex-Brush®
a significant increase in the detection of all categories Combi vs. cervical brush + Ayre’s spatula) for cervical
considered abnormal after the establishment of LBC. harvesting in LBC, aiming to evaluate their effectiveness
Also, one of the topics evaluated was the adequacy of the in obtaining endocervical cells, as well as the accuracy for
sample. Conventional cytology showed a higher occur- detection of NIC 2+. They observed that Cervex-Brush®
rence of unsatisfactory cases than LBC. In Turkey, Budak Combi was superior to the cervical brush + Ayre’s spatu-
et al. [5] published a retrospective study to compare the la for endocervical sampling (82.7 vs. 74.6%) and more
results of cytological exams from 47,954 patients between sensitive (48.6 vs. 33.9%) for detecting NIC 2+ lesions.
2008 and 2014, performed by conventional cytology and Kituncharoen et al. [12] compared the rates of unsat-
LBC. There was no significant difference regarding the isfactory samples and the detection of epithelial abnor-
occurrence of abnormalities. malities amongst 23,030 cervical samples collected by
Jeong et al. [6] studied 38,956 gynecologic cytopathol- conventional cytology and BD SurePath®. They conclud-
ogy reports using conventional cytology and LBC (from ed that there was no difference in the occurrence of un-
3 different manufacturers). It only addressed the inci- satisfactory samples (0.1 vs. 0.1%). The detection of high-
dence of unsatisfactory samples. The study concluded grade and glandular squamous abnormalities was also the
that LBC resulted in 1.26% of unsatisfactory samples, same. However, they observed that the detection of low-
whereas conventional cytology resulted in 3.31%. In 2016, grade abnormalities in squamous cells was significantly
Rozemeijer et al. [7] retrospectively studied more than 6 greater with the LBC (7.7 vs. 11.5%). In 2019, Gupta et al.
million cytological reports on conventional cytology and [13] compared the performance of a low-cost LBC tech-
2 LBC (BD SurePath® and ThinPrep®). BD SurePath® nique (EziPREP®) with conventional cytology. It was a
showed a 12% increase in the detection of epithelial atyp- cross-sectional split-sample study conducted on 515
ia (moderate dysplasia or more) compared with conven- women. The rate of unsatisfactory samples favored con-
tional cytology. ThinPrep® did not show any advantage ventional cytology (1 vs. 1.3%), but the differences in the
compared with conventional cytology in terms of sensi- detection of epithelial abnormalities and pathogenic mi-
tivity. The incidence of unsatisfactory samples or the de- croorganisms were not statistically significant, nor was
tection of pathogenic microorganisms was not addressed. the cytohistological correlation (96% for both tech-
In Brazil, Etlinger-Colonelli et al. [8] analyzed 41,264 niques).
gynecological samples comparing conventional cytology Pun et al. [14] conducted a comparative study between
and BD SurePath®. The increase in the detection of ab- conventional cytology (1,180 samples) and LBC (1,160
normal results rose from 7.80 to 11.57% when using LBC. samples). The percentage of unsatisfactory samples was
The incidence of low-grade lesions (LSIL) was the main lower in the LBC group (1.2 vs. 3.9%), and there was an
reason for the increase in sensitivity. As for the incidence increase in the detection of epithelial atypia (ASC-US+)
of unsatisfactory samples, it was decreased from 3.50 to when LBC was implemented (3.77 vs. 2.71%). Kaza et al.
0.25%. Longatto-Filho et al. [9] analyzed 218,594 conven- [15] compared conventional cytology and BD SurePath®
tional cytology and BD SurePath® samples. When using in terms of their sensitivities for detecting pathogenic mi-
conventional cytology, 3% of the samples were unsatis- croorganisms. Their findings suggested that both meth-
factory for analysis, whereas when using BD SurePath®, ods are equally valuable for this purpose.
the rate was only 0.3%. As for the detection of high-grade The main purpose of this study is to compare the sen-
lesions (HSIL), they observed the same percentage for sitivity for the detection of neoplastic and preneoplastic
both methods; however, the LSIL percentage was higher epithelial atypia, as well as the positive predictive value of
for LBC (2.2 vs. 0.7%). The index of positive results in- 3 methodologies, conventional cytology and LBC (BD
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International Academy of Cytology
Materials and Methods Between January 2007 and December 2018, during an
11-year study period, 24,529 cytology reports were re-
Samples viewed and categorized, according to TBS. Table 2 pres-
This is a retrospective study where the cytology samples and ents all the reporting results for the 3 techniques we em-
reports were obtained from the Pathology Service in the tertiary ployed. We also assessed the rate of unsatisfactory sam-
care center of the Brazilian Navy Hospital, Hospital Naval Marcílio
Dias (HNMD), Rio de Janeiro. This study obtained Institutional ples and the sampling of the SCJ.
Ethics Committee clearance before the commencement of the re- Interestingly, when we examined the specimen ade-
search. The reference numbers are CONEP/Plataforma Brasil, quacy, the percentage of unsatisfactory samples was
CAAE 06468819.2.000.5256, and authorization 3.208.007, Sep- smaller for conventional cytology (0.20%) when com-
tember 9, 2019. pared with BD SurePath® (1.08%). Nonetheless, there
The reports/samples were divided into 3 groups. The first
group consisted of 10,742 samples prepared by conventional cytol- was no statistical difference when comparing the 2 LBC,
ogy from January 2007 to December 2016. The second group stud- ThinPrep® (0.56%) and BD SurePath® (1.08%). The rate
ied was represented by 1,258 samples from January 2012 to July of unsatisfactory samples we observed for conventional
2013. They were processed using LBC ThinPrep® 2000 Hologic cytology is significantly smaller, insofar as reflecting the
(Marlborough, MA, USA), and Ayre’s spatula, endocervical sam- continuing training of the gynecology staff of HNMD for
pling brush, and the PreservCyt® Solution were employed for har-
vesting the samples. In the third group, we analyzed 12,529 reports a very long time. There is a residency medical program
of gynecological cytology using LBC BD SurePath® from August and a fellowship program in HNMD. We acknowledge
2013 to December 2018. For harvesting the samples, BD Sure- that this rate might not be reproducible in all cases. Con-
Path® Vial and Brush/Spatula Collection Kit were used. tinuous education and quality management programs for
The 24,529 cytology results were plotted in a table and catego- sample takers may not be a reality for some institutions
rized according to the Bethesda system (TBS) [16]. The following
variables were considered: negative for malignancy, ASC-US, and hospitals. Therefore, we believe this is the key point
LSIL, ASC-H, HSIL, squamous cell carcinoma, AGC, adenocarci- why our unsatisfactory rate for conventional cytology was
noma, and other malignant neoplasms. The presence of the follow- considerably small. Occasionally, the sample taker might
ing organisms was also evaluated: Trichomonas vaginalis, fungal not, for various reasons, accurately access the SCJ or even
organisms morphologically consistent with Candida spp., the shift the cervix itself. It is a critical step in terms of the institu-
in flora suggestive of bacterial vaginosis, bacteria morphologically
consistent with Actinomyces spp., and cellular changes consistent tions’ quality management program as a whole. The sam-
with herpes simplex virus. We verified the sampling of the SCJ (the ple taker skills should not be taken for granted and might
presence of endocervical cells and metaplastic cells) and the rate of be assessed periodically.
unsatisfactory samples. In our daily routine, we observed that the main causes
Whenever necessary, the patients were referred to colposcopy of unsatisfactory samples for conventional cytology are
and biopsied, according to TBS and the Brazilian guidelines for
cervical cancer screening [17]. Therefore, we correlated the cytol- obscuring blood/white blood cells, interfering substanc-
ogy results of the patients that were biopsied with their histopath- es, and cellularity excess. The percentage of unsatisfac-
ological result counterpart. The aim was to compare the positive tory samples we observed for LBC is comparable to the
predictive value for each of the cytology techniques (conventional literature [6, 13, 14]. They were higher when comparing
cytology, ThinPrep®, and BD SurePath®). The data were obtained to LBC, possibly to the adaptation of the gynecology staff
through direct search in registry books, Excel® sheets, medical re-
cords, cytology results plotted in the laboratory software Com- to the new technique when it was implemented. As for the
plab®, and printed medical files. LBC, we noticed that scanty squamous cellularity was the
main reason for rejection.
Statistics The next evaluated point was the presence of organ-
We used Pearson’s χ2 test to check the existence of a significant isms in the samples. We perceived no statistical difference
difference between the techniques studied (conventional cytology,
LBC ThinPrep®, and BD SurePath®) as to the proportion of oc- between conventional cytology (7.52%) and ThinPrep®
currence of the test results. In cases where the difference was sig- (5.80%), notwithstanding, BD SurePath® showed consid-
nificant, we performed a post hoc test with Bonferroni correction. erable superiority (16.94%).
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International Academy of Cytology
Bold: statistically significant difference. ASC-US, epithelial atypia; LSIL, low-grade lesions; HSIL, high-grade lesions. a Fisher’s exact
test.
Cervical intraepithelial neoplasia most commonly oc- Path® (67.08%), followed by ThinPrep® (50.40%) and
curs at the SCJ, a transitional zone. Sometimes, it is a chal- conventional cytology (39.53%). These results endorse
lenge to obtain an adequate sample. When we analyzed the better sensitivity for detecting atypia when using BD
the sampling of the SCJ, meaning the presence of well- SurePath®.
preserved endocervical and squamous metaplastic cells, From the total of 24,529 cytology reports, we recog-
the technique that showed the best result was BD Sure- nized 1,419 results considered atypical/abnormal, mean-
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International Academy of Cytology
Interpretation/result
NILM 10,154 (94.52) 11,588 (92.49) 1,204 (95.71)
ASC-US 295 (2.75) 436 (3.48) 15 (1.19)
LSIL 143 (1.33) 197 (1.57) 12 (0.95)
ASC-H 29 (0.27) 49 (0.39) 13 (1.03)
HSIL 30 (0.28) 61 (0.49) 4 (0.32)
Carcinoma 17 (0.16) 4 (0.03) 1 (0.08)
AGC (either NOS or favor neoplastic) 34 (0.32) 47 (0.38) 2 (0.16)
Adenocarcinoma 17 (0.16) 5 (0.04) 0 (0.00)
Other malignant neoplasms 1 (0.01) 7 (0.06) 0 (0.00)
Unsatisfactory 22 (0.20) 135 (1.08) 7 (0.56)
Organisms 808 (7.52) 2,122 (16.94) 73 (5.80)
SCJ sampling 4,246 (39.53) 8,405 (67.08) 634 (50.40)
ASC-US LSIL, ASC-H HSIL AGC (either NOS or Other malignant Total, n (%)
n (%) carcinoma, n (%) favor neoplastic) neoplasms, n (%)
adenocarcinoma, n (%)
ing ASC-US or higher (Table 3). They were categorized conventional cytology (0.71%). We did not observe any
into 4 different groups: ASC-US and LSIL; ASC-H, HSIL, statistical difference between ThinPrep® versus BD Sure-
and carcinoma; AGC (either NOS or favor neoplastic) Path®, both techniques proved to be superior to conven-
and adenocarcinoma, and other malignant neoplasms. tional cytology.
According to the protocols adopted in the studied hos- We assume the higher percentage of the ThinPrep®
pital, the patients are followed after 6 months whenever atypical results (1.43%) resemble false-positive results
they have results of ASC-US or LSIL. We observed the when compared with conventional cytology and BD
following rates of detection for this group: BD SurePath® SurePath®. This is critical when choosing the ideal tech-
(5.05%), followed by conventional cytology (4.08%) and nique, but it should be correlated to the positive predic-
ThinPrep® (2.15%). tive value (PPV).
According to TBS [16] and the Brazilian guidelines for In our study, 321 patients were reported with a result
cervical cancer screening [17, 18], whenever the patients of ASC-H or higher. They were referred to colposcopy
have a result of ASC-H or higher, they are referred to col- and biopsy, but only 200 patients returned to the hospital
poscopy and biopsy. Hence, in the next group of results, and were effectively biopsied. Accordingly, we compared
we investigated ASC-H, HSIL, and squamous cell carci- their cytology reports with their histopathological result
noma, and we verified the following results for each tech- counterpart (Table 4). Then, we assessed the PPV for each
nique: ThinPrep® (1.43%), BD SurePath® (0.91%), and of the techniques. We observed the following PPV: Thin-
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International Academy of Cytology
Bold: statistically significant difference. ASC-US, epithelial atypia; LSIL, low-grade lesions; HSIL, high-grade lesions.
Prep® (61.9%), conventional cytology (79.6%), and BD fixation, and preparation of slides. The fixation process
SurePath® (79.1%). consists of collecting cervical cells with a brush and dis-
As we summarized our data considering the presence persing the material in a preservative liquid right on site,
of atypical/abnormal cells, whether squamous or glandu- for further processing and assembly of the slides in the
lar, we verified that BD SurePath® detected more of these laboratory, using an automated and controlled method-
cells (6.44%) in comparison with conventional cytology ology. It was a milestone considering advances in the fol-
(5.28) and ThinPrep® (3.73%) (Table 5). These results as- lowing aspects:
sociated with the PPV indicate that, in our study, the most 1. Higher potential for detecting epithelial lesions
sensitive technique for cervical cancer screening is BD 2. Diminishing interferences (such as red blood cells and
SurePath®. We did not observe any statistical difference leukocytes) that obscure the slides in conventional cy-
between the results observed when using ThinPrep® and tology
conventional cytology. 3. Better distribution of epithelial cells in the preservative
liquid medium in the slide, thereby reducing the over-
lap of cells
Discussion/Conclusion 4. Better sampling of the cells onto the slide as the entire
collection of cells is transferred to the flask with the
In 2012, the Pathology Service of Hospital Naval Mar- preservative medium
cílio Dias implemented LBC, an extraordinary technique 5. Cells are better preserved, therefore better dyed and
promoting a breakthrough in cervical harvesting, sample more likely to be morphologically examined
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International Academy of Cytology
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