1. bookVolume 76 (2022): Issue 1 (January 2022)
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1732-2693
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Correlation between brush cytology results and histopathological examination in diagnostic evaluation of precancerous conditions and laryngeal cancer: A prospective study

Published Online: 10 May 2022
Volume & Issue: Volume 76 (2022) - Issue 1 (January 2022)
Page range: 149 - 156
Received: 09 Sep 2021
Accepted: 03 Feb 2022
Journal Details
License
Format
Journal
eISSN
1732-2693
First Published
20 Dec 2021
Publication timeframe
1 time per year
Languages
English
Abstract Introduction

The aim of the paper was to demonstrate that brush cytology can be useful in diagnostic evaluation of precancerous states and laryngeal cancer.

Materials and Methods

Ninety-two patients were analyzed. The control group included patients with benign laryngeal lesions, while the study group was composed of patients in whom a precancerous condition or laryngeal cancer was suspected. Material for histopathological and cytological examination was collected during a laryngeal microsurgery. The authors analyzed the consistency of the results of cytological and histopathological examination in the diagnostic evaluation of precancerous conditions and laryngeal cancer.

Results

Comparing diagnoses based on cytological examination with the results of histopathological examinations, the authors observed that there was a strong and statistically significant (p<0.001) correlation between the results. The accuracy of brush cytology in the conducted study indicates that the sensitivity and specificity of the test reaches 90.09% and 93.5% with 4 false negative and 3 false positive results. Positive prediction reached 93% and negative prediction reached 91.5%.

Conclusions

Brush cytology of the larynx may be useful in screening and as an auxiliary test in diagnostic evaluation of precancerous conditions and laryngeal cancer.

Keywords

Introduction

Squamous cell carcinoma (SCC) constitutes approximately 95% of laryngeal malignancies and is the most frequent malignancy in the neck and head region, with a 5-year survival rate of 50% [1, 2]. SCC is diagnosed on the basis of histopathological examination of the compromised tissue. The examination, however, is not used to monitor the condition of patients after cancer treatment. Frequent biopsies conducted under general anesthesia are associated with perioperative risk as well as a risk of bleeding or infection. They also require hospitalization and recovery after the procedure. Material for histopathological examination can also be obtained during videolaryngoscopy conducted under local anesthesia in an outpatient setting; however, it should be taken into account that bleeding or even laryngospasm may occur during the procedure [3]. In patients who underwent cancer treatment, follow-up consists in conducting laryngological examinations and imaging. Follow-up of a patient with a history of laryngeal cancer is essential, both due to the high relapse rate and frequent occurrence of a second primary cancer in this area, which is a result of the negative effect of carcinogenic factors on the entire mucous membrane of the upper digestive and respiratory tract [4, 5, 6]. Considering the 5-year survival period, the considerable percentage of laryngeal cancer relapses as well as the economic aspects associated with hospitalization and recovery in the case of surgical biopsy, the search for other, less invasive, repeatable and comparably sensitive diagnostic methods seems legitimate. Attempts to use brush cytology in the case of laryngeal diseases were described decades ago, and the first reports published by J. W. Ayre are from 1954 [7]. Currently, the method is used in screening and early diagnostic evaluation of intraepithelial uterine cervix neoplasia, lung and bronchial cancer, as well as dysplastic lesions and cancer of the oral cavity [8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18].

Materials and Methods

The study involved 92 patients who were treated at the Clinic of Otolaryngology Head and Neck Surgery, 4th Military Clinical Hospital with Polyclinic in Wroclaw, in the years 2019 – 2020. Approval of the Bioethics Committee of the Wroclaw Medical University was obtained. The study was conducted in accordance with the recommendations of the Helsinki Declaration, Clinical Trial Registration Number KB-519/2018. All patients received detailed information on the assumptions and stages of the study and gave written consent to participate therein. The inclusion criteria were morphological lesions in the larynx observed during an outpatient laryngological examination. A history of radio-therapy treatment of the head and neck region was the exclusion criterion. Data on patients were obtained from their medical records: medical history, surgical protocol, results of histopathological examination. Within the framework of preoperative diagnostic evaluation, patients underwent indirect laryngoscopy as well as endoscopic examination of the larynx with archiving of photographic documentation. Patients underwent a diagnostic and surgical procedure: laryngeal microsurgery under general anesthesia with the use of a microscope and Kleinsasser set. First, material for cytological examination was collected with the use of a sterile, standard cytological brush of 195 mm in length. After reaching the level of the examined lesion, the physician pressed the brush against it and performed several 360-degree rotational movements while moving the brush along the long axis. The material collected during this procedure was applied to a microscope slide by shaking the material off the brush and gently spreading it. It was then preserved with the use of Cytofix, applied to the slide from a distance of 25 cm for 1 second. After being dried for 4 minutes, the material was stained with hematoxylin and eosin. Tissue material for histopathological examination was collected from the same site. It was immediately preserved in a 10% solution of buffered formalin. Cytology evaluation was conducted with the use of the scale shown in Table 1. This scale is the authors’ own modification of the Bethesda scale, which is commonly used for the evaluation of cervical cytology. All smears were performed by conventional methods. Two out of 92 preparations were not suitable for evaluation. The remaining 90 preparations were evaluated. Results of cytological examination were categorized into 5 main groups:

cytologically benign lesions

LSIL lesion

HSIL lesion

HSIL lesion with features of invasion

ASC-US

Cytological evaluation of laryngeal smear

Type of cytological preparation ConventionalMade using a different method
Overall quality of the smear Suitable for cytological evaluationSuitable for cytological evaluation, driedNot suitable for cytological evaluation (technical procedure was not performed, or technical procedure was performed but material is too dry, incorrectly preserved, cell concentration is low, material is not legible due to numerous inflammatory cells, erythrocytes)
Number of cells in the smear High cell concentration K1Moderate number of cells K2Low cell concentration K3
Erythrocyte count in the smear High erythrocyte count E1Low/moderate erythrocyte count E2Erythrocytes absent E3
Severity of inflammation Minor inflammation INF1Moderate inflammation INF2Severe inflammation INF3
Type of inflammatory cells Lymphocytes LGranulocytes GLymphocytes and granulocytes L and G
General characteristics of the smear No intraepithelial neoplasia or cancer, only normal stratified squamous epithelial cells are presentAbnormal cytologyCells other than stratified squamous epithelial cells are present in the smear, glandular epithelium cells are present
Abnormal epithelial cells Atypical squamous cells of undetermined significance ASC-USLow-grade intraepithelial lesion LSILHigh-grade squamous intraepithelial lesion HISLHigh-grade squamous intraepithelial lesion with features that raise suspicion of invasion (keratin pearl, keratin bundles, pathological mitoses)

An analogous division was applied while grouping the results of histopathological examination:

histopathologically benign lesion

low-grade intraepithelial neoplastic lesion

high-grade intraepithelial neoplastic lesion

invasive cancer

The collected sociodemographic data were statistically analyzed with the use of the STATISTICA vs. 13.3 PL software. Nominal qualitative values (e.g., sex) are presented in cross tabulations as size (n) and proportion (%). Pearson’s chi-square test was used to assess the significance of the relationship between two qualitative variables. Quantitative variables (e.g., age) are presented in tables as mean values (M) and standard deviations (SD) as well as statistics of location: medians (Me), lower quartiles (Q51), upper (Q3), lowest (Min) and highest values (Max). The consistency of the empirical distribution of quantitative variables with the theoretical Gaussian distribution was verified with the use of the W Shapiro-Wilk normality test. Homogeneity of variance was verified using the Levene’s test. The significance of differences of average values of quantitative variables in two groups was verified with the use of the U Mann-Whitney test. Cohen’s kappa reliability coefficient was used to assess the consistency of the results of cytological and histopathological examinations of surgical biopsy collected from the same site. Coefficients weighted with quadratic weights were used due to the categorical nature of the diagnoses.

Results
Patients’ characteristics

The study involved 92 patients, including 34 women (37.0%), aged 26 to 85 (mean M8 = 62.0; standard deviation SD = 11.0 years), treated for laryngeal diseases. Laryngeal cancer or leukoplakic lesions were suspected in 67 (72.8%) patients, who were assigned to the study group (B). In 25 (27.2%) patients diagnosis was benign (polyp, cyst, Reinke’s edema), and they were assigned to the control group (K). (See Table 2.)

General characteristics of patients

Feature (variable) Group B Group K Total B vs K p
N = 67 N = 25 N = 92
n (%) n (%) n (%)
Sex: <0.001
Female 16 23.9% 18 72.0% 34 37,0%
Male 51 76.1% 7 28.0% 58 63,0%
Age: 0.011
M ± SD 64.1 ± 8.6 56.3 ± 14.4 62.0 ± 11.0
Me [Q1; Q3] 66 [60; 70] 59 [42; 67] 64 [57; 69]
Min – Max 26 - 79 34 - 85 26 - 85

n - group size; % - proportion; M - mean; SD - standard deviation; Me - median (50. percentile); Q1 - lower quartile (25. percentile); Q3 - upper quartile (75. percentile); Min - lowest value; Max - highest value; p - test significance level

Clinical characteristics of both groups of patients are presented in Table 3.

Clinical characteristics of patients

Feature (variable) Group B Group K Total B vs K p
N = 67 N = 25 N = 92
n (%) n (%) n (%)
Diagnosis: <0.001
Laryngeal cancer 57 85.1 0 0.0 57 62.0
Leukoplakia 10 14.9 0 0.0 10 10.9
Polyp 0 0.0 10 40.0 10 10.9
Reinke’s edema 0 0.0 10 40.0 10 10.9
Cyst 0 0.0 5 20.0 5 5.3
Results of histopathological examination <0.001
FI - benign lesion 21 31.3% 25 100.0% 46 50.0%
LSIL 7 10.4% 0 0.0% 7 7.6%
HSIL 6 9.0% 0 0.0% 6 6.5%
Malignant lesion 33 49.3% 0 0.0% 33 35.9%
Results of cytological examination: N = 67 N = 23 N = 90 <0.001
FI - benign lesion 20 29.9% 23 100.0% 43 47.8%
LSIL 11 16.4% 0 0.0% 11 12.2%
HSIL 12 17.9% 0 0.0% 12 13.3%
HISL* (with features of invasion) 21 31.4% 0 0.0% 21 23.3%
ASC-US 3 4.5% 0 0.0% 3 3.3%

Due to the adopted division criterion, statistically significant correlation occurs between the initial diagnosis made on the basis of the results of cytological (Fig. 1) and the histopathological examination (Fig. 2) as well as whether patients were assigned to group B or K (p < 0.001) based on final diagnosis.

Fig. 1

Number (percentage) of patients in groups differing in terms of final and initial diagnosis on the basis of cytological examination results (FI – normal result, benign lesions; LSIL – low-grade lesion; HSIL – high-grade lesion; HSIL* – high-grade lesion with features of invasion; ASC-US – atypical cells of undetermined significance) and results of independence test

Fig. 2

Number (percentage) of patients in groups differing in terms of clinical diagnosis and result of histopathological examination as well as result of independence test

Comparison of diagnoses made on the basis of cytological examination with histopathological results is presented in Table 4.

Number (proportion) of diagnoses in 90 patients with laryngeal diseases made based on results of cytological and histopathological examinations

Result of brush cytology Result of histopathological examination
Benign lesionN = 44 LSILN = 7 HSILN = 6 Malignant lesionN = 33
FI - benign lesion 40 (44.4%) 0 (0.0%) 0 (0.0%) 3 (3.3%)
LSIL 4 (4.4%) 7 (7.8%) 0 (0.0%) 0 (0.0%)
HSIL 0 (0.0%) 0 (0.0%) 6 (6.7%) 6 (6.7%)
HISL* - with features of invasion 0 (0.0%) 0 (0.0%) 0 (0.0%) 21 (23.3%)
ASC-US - abnormal result 0 (0.0%) 0 (0.0%) 0 (0.0%) 3 (3.3%)

A strong, statistically significant (p < 0.001) correlation was observed between diagnoses made on the basis of cytological and histopathological examinations (Fig. 3).

Fig. 3

Number (percentage) of patients in groups differing in terms of initial diagnosis and diagnosis made based on results of histopathological and cytological examination and results of independence test

Spearman’s correlation coefficient and the value of Cohen’s kappa reliability coefficient confirm that there is a strong correlation between diagnoses made on the basis of the results of histopathological and cytological examination (Fig. 4).

Fig. 4

Scatter plot of cytology and histopathology results

The following values of diagnostic accuracy indices of the test were estimated in order to estimate the accuracy of diagnosis based on cytological examination in relation to the results of histopathological examination (the gold standard): sensitivity, specificity, accuracy of diagnosis, actual disease rate, predicted frequency of the disease in individuals with a positive test result (+) (positive prediction) and predicted frequency in individuals with a negative test result (−) (negative prediction).

Results of cytological and histopathological examination (Table 3) were transformed into dichotomous variables:

positive results (+): LSIL, HSIL or HSIL with features of invasion (in cytology),

negative result (−): benign lesion

Table 5 presents diagnostic accuracy evaluation based on a study of 87 patients.

The following designations are used in Table 5:

PD - true positive results, (TP)

FD - false positive results, (FP)

FU - false negative, (FN)

PU - true negative, (TN)

Test sensitivity = PD/(PD + FD)

Test specificity = PU/(FD + PU)

Accuracy of diagnosis = (PD + PU)/(PD + FD + FU + PU)

Actual frequency of the disease = (PD + FU)/(PD + FD + FU + PU)

Predicted frequency of the disease in individuals with a positive test result (+) positive prediction PPV = PD/(PD + FD)

Predicted frequency of lack of the disease in individuals with a negative test result (−) negative prediction NPV = FU/(FU+ PU)

Likelihood ratio for a positive test result, LR+ = (sensitivity)/(1 - specificity)

Likelihood ratio for a negative test result, LR− = (sensitivity)/(1 - specificity)

The accuracy of brush cytology as a diagnostic test for laryngeal cancer

Cytological examination The actual status – “gold standard” Histopathological examination
(+) (−) Total
(+) 40 (PD) 3 (FD) 43 (PD + FD)
(−) 4 (FU) 43 (PU) 47 (FU + PU)
44 (PD + FU) 46 (FD + PU) 87 (PD + FD + FFU + PU)

Test sensitivity = (40/44) × 100 = 90.9%

Test specificity = (43/46) × 100 = 93.5%

Accuracy of diagnosis = (83/87) × 100 = 92.2%

Positive prediction = (40/40) = 93.0%

Negative prediction = (15/25) = 91.5%

LR+ reliability index = 13.94

LR− reliability index = 0.10

It is assumed that tests with LR+ around 10 and above, or LR-from 0.1 and below are often decisive. Cytological examination meets both of these criteria. In addition, weighted Cohen’s kappa coefficient was used for the assessment of the reliability of double examinations of collected tissues. Results of the comparisons are presented in Table 6.

Observed numbers of the classification of laryngeal findings conducted by a cytologist and histopathologist, and Cohen’s kappa value with quadratic weights and standard errors for κ

Cytologist Histopathologist
Benign lesion LSIL HSIL Malignant lesion
Benign lesion 40 0 0 3
LSIL 4 7 0 0
HSIL 0 0 6 6
HISL with features of invasion 0 0 0 21
N = 87; Cohen’s kappa coefficient κ = 0.732; SE = 0.020; p < 0.0001

Weighted Cohen’s kappa for 87 patients diagnosed using two methods is κ = 0.732 (p < 0.001). Cohen’s kappa coefficient with quadratic weights is the same as intraclass correlation coefficient. The obtained result (p-value < 0.001) makes it possible to reject the null hypothesis on the lack of consistency between these evaluations, which indicates that opinions of both diagnosticians (cytologist and histopathologist) are consistent. Based on the classification proposed by Altman, Landis, and Koch, revealed in Table 7, we can conclude that results of cytology and histopathology are highly consistent.

Discussion

Analysis of the general characteristics of the patients involved in the described study revealed that their age and sex were statistically significant (p<or=0.001). In the study group, most patients histopathologically diagnosed laryngeal squamous cell carcinoma were in their sixties with a significant predominance of the male sex. The majority of patients in the control group, on the other hand, were women and the mean age in the group was 56.3. Comparing the initial clinical diagnosis with the result of histopathological examination in the control group, we obtain a consistency of 100%. In the case of cytological examination, 2 out of 25 smears were not fit for analysis, and no signs of cellular atypia were observed in any of the 23 analyzed images.

In the case of the study group, which included 67 individuals in whom the morphological image of the larynx suggested a potentially malignant lesion, histopathological examination revealed benign lesions in 21 cases and in 46 cases showed low-degree dysplasia (7.46), high-degree dysplasia (6/46), or squamous cell cancer (33/46). In the analysis of the results of cytological examination conducted in the study group, benign lesions were observed in 20 smears, while 3 examinations revealed ASC-US, atypical squamous cells of undetermined significance. Potentially malignant or malignant lesions were observed in 43 examinations, 11, 12, and 21 results for LSIL, HSIL, and HSIL with features of invasion (Table 3). Comparing diagnoses based on cytological examination with the results of histopathological examination, we observed a strong, statistically significant (p < 0.001) correlation between diagnoses made on the basis of cytological and histopathological examination (Table 5, Fig. 4) The accuracy of brush cytology as a diagnostic test for laryngeal cancer in the conducted study indicates that the sensitivity and specificity of the test reaches 90.09% and 93.5% with 4 false negative and 3 false positive results. Positive prediction, the predicted frequency of the disease in individuals who tested positive (+) is 93%, and negative prediction, the predicted frequency of the lack of the disease in individuals who tested negative (−), is 91.5%. The likelihood index was: LR+ 13.94 i LR- 0.10. Such values of likelihood indices are frequently decisive, and cytological examination meets both of these criteria. In addition, we obtained kappa coefficient (k = 0.732) with quadratic weights identical to the intraclass correlation coefficient. The obtained result (p-value < 0.001) shows that diagnoses made by both diagnosticians, the cytologist and the histopathologist, are consistent. Referring to Altman, Landis, and Koch classification, we can conclude that the results of histopathology and cytology are highly consistent (Table 7).

In the case of laryngeal cancer, the most common malignancy of the head and neck, we can achieve satisfactory results of treatment when the disease is diagnosed at an early stage [19]. In the advanced stage of the disease, only 22% to 50% of patients survive 5 years [4]. Histopathological examination constitutes the “gold standard” in diagnostic evaluation of laryngeal cancer [20]. It is a reliable, yet time-consuming examination, in the case of which tissue is collected with the use of laryngeal microsurgery performed under general anesthesia during hospitalization. Histopathological diagnoses of low- or moderate-grade dysplasia require careful observation of the patient, due to the risk of intraepithelial transformation into high-grade dysplasia, carcinoma in situ, or an invasive carcinoma. Sometimes clinicians also deal with the problem of a discrepancy between the results of clinical and histopathological examination. In such circumstances, clinicians repeat surgical biopsies, which carries further risk of perioperative complications, may contribute to impairing the function of the voice organ and constitutes an economic burden on the health care system. A diagnostic tool that is widely available, minimally invasive, cheap and simple to use, and that can be applied both in diagnostic evaluation conducted on an outpatient basis and at the hospital, is needed for early diagnostic evaluation of precancerous conditions and laryngeal malignancies as well as the follow-up after surgical treatment.

For years, brush cytology has been used as a screening examination in diagnostic evaluation of uterine cervical cancer, even though the diagnostic accuracy of cytological smears ranges from 41% for ASC-US diagnoses to 73% for HSIL diagnoses, with many false positive and false negative results [21]. The main drawback of cytological examination is that during the examination it is impossible to obtain the level of the basal membrane and the dispersion of cancer cells in relation thereto, which makes it impossible to differentiate between high-grade dysplasia, carcinoma in situ, or invasive carcinoma. Therefore, in the case of cytological examinations, a different classification should be used for categorizing cytologically benign lesions, LSIL, HSIL, and HSIL with features of invasion or ASC-US.

The role of brush cytology in diagnostic evaluation of laryngeal diseases has been studied for years. In the 1980s, in a large group of 350 patients, Lundgreen et al. obtained sensitivity and specificity of brush cytology of 83% and 84% in diagnostic evaluation of moderate- and high-degree dysplasia and laryngeal cancer. The results obtained in this study are much better. False negative results obtained from patients previously treated with radiotherapy due to head and neck cancer may be different. In the present study, such criterion was used to exclude patients from the study group [22]. Results of analysis similar to those described were obtained in 1994 by Waloryszak and Makowska, whose research revealed examination consistency of 91% in a group of 70 patients with laryngeal cancer; the other cases were false negative results [23]. In the study conducted by Malamou-Mitsi et al., the obtained specificity and sensitivity were equal to 100% and 93%, with one false negative result in the case of laryngeal non-Hodgkin lymphoma [24]. In 2006, researchers conducted a study aimed at diagnosing cancer of the glottis with the use of brush cytology and laryngostroboscopy performed prior to the procedure of cellular material and specimen collection. The sensitivity of this diagnostic method combining both examinations was as high as 97% [25]. Chatziavramidis et al. analyzed the consistency of brush cytology and liquid base cytology (LBC) with histopathological examination. Exclusion criteria in the study group included a history of radiotherapy of the head and neck region and cardiovascular or pulmonary comorbidities. Despite the restrictions in the selection of the study group and adding liquid base cytology to diagnostic evaluation, the authors obtained a specificity of 90% and sensitivity of 85%, which is worse than in the conducted analysis.

Conclusions

In the case of laryngeal cancer, brush cytology does not compete with histopathological examination and should not be decisive in the making of a cancer diagnosis. The described analysis, however, shows that the results of the discussed studies are significantly consistent. Such indicators as sensitivity and specificity as well as positive and negative prediction exceeding 90% prove that brush cytology may be a very good auxiliary diagnostic tool in the case of laryngeal cancer. It could also be used in screening diagnostic evaluation for laryngeal cancer when monitoring patients with dysplasia, or evaluating distant effects of surgical treatment performed within the framework of both inpatient and outpatient procedures.

Fig. 1

Number (percentage) of patients in groups differing in terms of final and initial diagnosis on the basis of cytological examination results (FI – normal result, benign lesions; LSIL – low-grade lesion; HSIL – high-grade lesion; HSIL* – high-grade lesion with features of invasion; ASC-US – atypical cells of undetermined significance) and results of independence test
Number (percentage) of patients in groups differing in terms of final and initial diagnosis on the basis of cytological examination results (FI – normal result, benign lesions; LSIL – low-grade lesion; HSIL – high-grade lesion; HSIL* – high-grade lesion with features of invasion; ASC-US – atypical cells of undetermined significance) and results of independence test

Fig. 2

Number (percentage) of patients in groups differing in terms of clinical diagnosis and result of histopathological examination as well as result of independence test
Number (percentage) of patients in groups differing in terms of clinical diagnosis and result of histopathological examination as well as result of independence test

Fig. 3

Number (percentage) of patients in groups differing in terms of initial diagnosis and diagnosis made based on results of histopathological and cytological examination and results of independence test
Number (percentage) of patients in groups differing in terms of initial diagnosis and diagnosis made based on results of histopathological and cytological examination and results of independence test

Fig. 4

Scatter plot of cytology and histopathology results
Scatter plot of cytology and histopathology results

The accuracy of brush cytology as a diagnostic test for laryngeal cancer

Cytological examination The actual status – “gold standard” Histopathological examination
(+) (−) Total
(+) 40 (PD) 3 (FD) 43 (PD + FD)
(−) 4 (FU) 43 (PU) 47 (FU + PU)
44 (PD + FU) 46 (FD + PU) 87 (PD + FD + FFU + PU)

Observed numbers of the classification of laryngeal findings conducted by a cytologist and histopathologist, and Cohen’s kappa value with quadratic weights and standard errors for κ

Cytologist Histopathologist
Benign lesion LSIL HSIL Malignant lesion
Benign lesion 40 0 0 3
LSIL 4 7 0 0
HSIL 0 0 6 6
HISL with features of invasion 0 0 0 21
N = 87; Cohen’s kappa coefficient κ = 0.732; SE = 0.020; p < 0.0001

Cytological evaluation of laryngeal smear

Type of cytological preparation ConventionalMade using a different method
Overall quality of the smear Suitable for cytological evaluationSuitable for cytological evaluation, driedNot suitable for cytological evaluation (technical procedure was not performed, or technical procedure was performed but material is too dry, incorrectly preserved, cell concentration is low, material is not legible due to numerous inflammatory cells, erythrocytes)
Number of cells in the smear High cell concentration K1Moderate number of cells K2Low cell concentration K3
Erythrocyte count in the smear High erythrocyte count E1Low/moderate erythrocyte count E2Erythrocytes absent E3
Severity of inflammation Minor inflammation INF1Moderate inflammation INF2Severe inflammation INF3
Type of inflammatory cells Lymphocytes LGranulocytes GLymphocytes and granulocytes L and G
General characteristics of the smear No intraepithelial neoplasia or cancer, only normal stratified squamous epithelial cells are presentAbnormal cytologyCells other than stratified squamous epithelial cells are present in the smear, glandular epithelium cells are present
Abnormal epithelial cells Atypical squamous cells of undetermined significance ASC-USLow-grade intraepithelial lesion LSILHigh-grade squamous intraepithelial lesion HISLHigh-grade squamous intraepithelial lesion with features that raise suspicion of invasion (keratin pearl, keratin bundles, pathological mitoses)

Clinical characteristics of patients

Feature (variable) Group B Group K Total B vs K p
N = 67 N = 25 N = 92
n (%) n (%) n (%)
Diagnosis: <0.001
Laryngeal cancer 57 85.1 0 0.0 57 62.0
Leukoplakia 10 14.9 0 0.0 10 10.9
Polyp 0 0.0 10 40.0 10 10.9
Reinke’s edema 0 0.0 10 40.0 10 10.9
Cyst 0 0.0 5 20.0 5 5.3
Results of histopathological examination <0.001
FI - benign lesion 21 31.3% 25 100.0% 46 50.0%
LSIL 7 10.4% 0 0.0% 7 7.6%
HSIL 6 9.0% 0 0.0% 6 6.5%
Malignant lesion 33 49.3% 0 0.0% 33 35.9%
Results of cytological examination: N = 67 N = 23 N = 90 <0.001
FI - benign lesion 20 29.9% 23 100.0% 43 47.8%
LSIL 11 16.4% 0 0.0% 11 12.2%
HSIL 12 17.9% 0 0.0% 12 13.3%
HISL* (with features of invasion) 21 31.4% 0 0.0% 21 23.3%
ASC-US 3 4.5% 0 0.0% 3 3.3%

General characteristics of patients

Feature (variable) Group B Group K Total B vs K p
N = 67 N = 25 N = 92
n (%) n (%) n (%)
Sex: <0.001
Female 16 23.9% 18 72.0% 34 37,0%
Male 51 76.1% 7 28.0% 58 63,0%
Age: 0.011
M ± SD 64.1 ± 8.6 56.3 ± 14.4 62.0 ± 11.0
Me [Q1; Q3] 66 [60; 70] 59 [42; 67] 64 [57; 69]
Min – Max 26 - 79 34 - 85 26 - 85

Number (proportion) of diagnoses in 90 patients with laryngeal diseases made based on results of cytological and histopathological examinations

Result of brush cytology Result of histopathological examination
Benign lesionN = 44 LSILN = 7 HSILN = 6 Malignant lesionN = 33
FI - benign lesion 40 (44.4%) 0 (0.0%) 0 (0.0%) 3 (3.3%)
LSIL 4 (4.4%) 7 (7.8%) 0 (0.0%) 0 (0.0%)
HSIL 0 (0.0%) 0 (0.0%) 6 (6.7%) 6 (6.7%)
HISL* - with features of invasion 0 (0.0%) 0 (0.0%) 0 (0.0%) 21 (23.3%)
ASC-US - abnormal result 0 (0.0%) 0 (0.0%) 0 (0.0%) 3 (3.3%)

Korampalli TS, Stafford ND. Expression of angiogenic growth factors in laryngeal carcinoma. Mol Clin Oncol. 2013; 1: 1013–1018. KorampalliTS StaffordND Expression of angiogenic growth factors in laryngeal carcinoma Mol Clin Oncol. 2013 1 1013 1018 Search in Google Scholar

Ustundag E, Kaur AC, Boyacı Z, Keskin G, Aydin O. Combined use of histopathology with touch smear cytology in biopsies of the larynx. Eur Arch Otorhinolaryngol. 2006; 263: 866–871. UstundagE KaurAC BoyacıZ KeskinG AydinO Combined use of histopathology with touch smear cytology in biopsies of the larynx Eur Arch Otorhinolaryngol. 2006 263 866 871 Search in Google Scholar

Saita V, Allegra E, Marino N, Trapasso S, Monea MC. Videolaryngoscopy during conscious sedation in patients not suitable for phonosurgery by microlaryngoscopy: A pilot study. J Otorhinolaryngol Relat Spec. 2017; 79: 185–190. SaitaV AllegraE MarinoN TrapassoS MoneaMC Videolaryngoscopy during conscious sedation in patients not suitable for phonosurgery by microlaryngoscopy: A pilot study J Otorhinolaryngol Relat Spec. 2017 79 185 190 Search in Google Scholar

Leemans CR, Braakhuis BJM, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011; 11: 9–22. LeemansCR BraakhuisBJM BrakenhoffRH The molecular biology of head and neck cancer Nat Rev Cancer. 2011 11 9 22 Search in Google Scholar

Ritoe SC, de Vegt F, Scheike IM, Krabbe PFM, Kaanders JHAM, den Hoogen FJA, Verbeek ALM, Marres HAM. Effect of routine follow-up after treatment for laryngeal cancer on life expectancy and mortality: Results of a Markov model analysis. Cancer, 2007; 109: 239–247. RitoeSC de VegtF ScheikeIM KrabbePFM KaandersJHAM den HoogenFJA VerbeekALM MarresHAM Effect of routine follow-up after treatment for laryngeal cancer on life expectancy and mortality: Results of a Markov model analysis Cancer 2007 109 239 247 Search in Google Scholar

Tirelli G, Zacchigna S, Biasotto M, Piovesana M. Open questions and novel concepts in oral cancer surgery. Eur Arch Otorhinolaryngol. 2016; 273: 1975–1985. TirelliG ZacchignaS BiasottoM PiovesanaM Open questions and novel concepts in oral cancer surgery Eur Arch Otorhinolaryngol. 2016 273 1975 1985 Search in Google Scholar

Glennie HR, Gilbert JG, Melcher DH, Linehan J, Wadsworth PV. The place of cytology in laryngeal diagnosis. Clin Otolaryngol Allied Sci. 1976; 1: 131–136. GlennieHR GilbertJG MelcherDH LinehanJ WadsworthPV The place of cytology in laryngeal diagnosis Clin Otolaryngol Allied Sci. 1976 1 131 136 Search in Google Scholar

Almangush A, Mäkitie AA, Triantafyllou A, de Bree R, Strojan P, Rinaldo A, Hernandez-Prera JC, Suárez C, Kowalski LP, Ferlito A, Leivo I. Staging and grading of oral squamous cell carcinoma: An update. Oral Oncology. 2020; 107: 104799. AlmangushA MäkitieAA TriantafyllouA de BreeR StrojanP RinaldoA Hernandez-PreraJC SuárezC KowalskiLP FerlitoA LeivoI Staging and grading of oral squamous cell carcinoma: An update Oral Oncology. 2020 107 104799 Search in Google Scholar

Andratschke M, Schmitz S, Hagedorn H, Nerlich A. Cytological and immunocytological monitoring of oropharyngeal dysplasia and squamous cell carcinomas. Anticancer Res. 2015; 35: 6517–6520. AndratschkeM SchmitzS HagedornH NerlichA Cytological and immunocytological monitoring of oropharyngeal dysplasia and squamous cell carcinomas Anticancer Res. 2015 35 6517 6520 Search in Google Scholar

Broglie MA, Jochum W, Förbs D, Schönegg R, Stoeckli SJ. Brush cytology for the detection of high-risk HPV infection in oropharyngeal squamous cell carcinoma. Cancer Cytopathol. 2015; 123: 732–738. BroglieMA JochumW FörbsD SchöneggR StoeckliSJ Brush cytology for the detection of high-risk HPV infection in oropharyngeal squamous cell carcinoma Cancer Cytopathol. 2015 123 732 738 Search in Google Scholar

Giti R, Hosseinzadeh M. Efficacy of bronchial washing and brushing cytology in the diagnosis of non-neoplastic lung diseases. Acta Med Iran. 2017; 55: 636–641. GitiR HosseinzadehM Efficacy of bronchial washing and brushing cytology in the diagnosis of non-neoplastic lung diseases Acta Med Iran. 2017 55 636 641 Search in Google Scholar

Gupta R, Yadav R, Sharda A, Kumar D, Sandeep A, Mehrotra R, Gupta S. Comparative evaluation of conventional cytology and a low-cost liquid-based cytology technique, EziPREPTM, for cervicovaginal smear reporting: A split sample study. Cytojournal. 2019; 16: 22. GuptaR YadavR ShardaA KumarD SandeepA MehrotraR GuptaS Comparative evaluation of conventional cytology and a low-cost liquid-based cytology technique, EziPREPTM, for cervicovaginal smear reporting: A split sample study Cytojournal. 2019 16 22 Search in Google Scholar

Gupta S, Shah JS, Parikh S, Limbdiwala P, Goel S. Clinical correlative study on early detection of oral cancer and precancerous lesions by modified oral brush biopsy and cytology followed by histopathology. J Cancer Res Ther. 2014; 10: 232–238. GuptaS ShahJS ParikhS LimbdiwalaP GoelS Clinical correlative study on early detection of oral cancer and precancerous lesions by modified oral brush biopsy and cytology followed by histopathology J Cancer Res Ther. 2014 10 232 238 Search in Google Scholar

Jajodia E, Raphael V, Shunyu NB, Ralte S, Pala S, Jitani AK. Brush cytology and AgNOR in the diagnosis of oral squamous cell carcinoma. Acta Cytol. 2017; 61: 62–70. JajodiaE RaphaelV ShunyuNB RalteS PalaS JitaniAK Brush cytology and AgNOR in the diagnosis of oral squamous cell carcinoma Acta Cytol. 2017 61 62 70 Search in Google Scholar

Lv S, Rui Wang R, Wang O, Han L, Tuo X, Hou H, Liu Y, Shi Z, Wang Q, et al. A novel solution configuration on liquid-based endometrial cytology. PLoS One. 2018; 13: 0190851. LvS Rui WangR WangO HanL TuoX HouH LiuY ShiZ WangQ A novel solution configuration on liquid-based endometrial cytology PLoS One. 2018 13 0190851 Search in Google Scholar

Mehrotra R, Hullmann M, Smeets R, Reichert TE, Driemal O. Oral cytology revisited. J Oral Pathol Med. 2009; 38: 161–166. MehrotraR HullmannM SmeetsR ReichertTE DriemalO Oral cytology revisited J Oral Pathol Med. 2009 38 161 166 Search in Google Scholar

Olms C, Hix N, Neumann H, Yahiaoui M, Remmerbach TW. Clinical comparison of liquid-based and conventional cytology of oral brush biopsies: A randomized controlled trial. Head Face Med. 2018; 14: 9. OlmsC HixN NeumannH YahiaouiM RemmerbachTW Clinical comparison of liquid-based and conventional cytology of oral brush biopsies: A randomized controlled trial Head Face Med. 2018 14 9 Search in Google Scholar

Russel CJ, Neidhardt HW, Mountain CF, Griffith KM. Cytodiagnosis of lung cancer. A report of a four-year laboratory, clinical and statistical studywith a review of the literature on lung cancer and pulmonary cytology. Acta Cytol. 1963; 7: 1–44. RusselCJ NeidhardtHW MountainCF GriffithKM Cytodiagnosis of lung cancer. A report of a four-year laboratory, clinical and statistical studywith a review of the literature on lung cancer and pulmonary cytology Acta Cytol. 1963 7 1 44 Search in Google Scholar

Mourad M, Jetmore T, Jategaonkar TA, Moubayed S, Moshier E, Urken ML. Epidemiological trends of head and neck cancer in the United States: A SEER population study. J Oral Maxillofac Surg. 2017; 75: 2562–2572. MouradM JetmoreT JategaonkarTA MoubayedS MoshierE UrkenML Epidemiological trends of head and neck cancer in the United States: A SEER population study J Oral Maxillofac Surg. 2017 75 2562 2572 Search in Google Scholar

Salvador-Coloma C, Cohen E. Multidisciplinary care of laryngeal cancer. J Oncol Pract. 2016; 12: 714–724. Salvador-ColomaC CohenE Multidisciplinary care of laryngeal cancer J Oncol Pract. 2016 12 714 724 Search in Google Scholar

Rokita W, Dariusz Skawiński D, Zmelonek-Znamirowska A, Kedzia W, Karowicz-Bilińska A, Spaczyński R, Spaczyński M. Results of pap smears and immunocytochemical detection of the p16 and Ki67 proteins in women with cervical intraepithelial neoplasia and cervical cancer. Ginekol Pol. 2012; 83: 822–826. RokitaW Dariusz SkawińskiD Zmelonek-ZnamirowskaA KedziaW Karowicz-BilińskaA SpaczyńskiR SpaczyńskiM Results of pap smears and immunocytochemical detection of the p16 and Ki67 proteins in women with cervical intraepithelial neoplasia and cervical cancer Ginekol Pol. 2012 83 822 826 Search in Google Scholar

Lundgren J, Olofsson J, Hellquist HB, Strandh J. Exfoliative cytology in laryngology: Comparison of cytologic and histologic diagnoses in 350 microlaryngoscopic examinations - a prospective study. Cancer. 1981; 47: 1336–1343. LundgrenJ OlofssonJ HellquistHB StrandhJ Exfoliative cytology in laryngology: Comparison of cytologic and histologic diagnoses in 350 microlaryngoscopic examinations - a prospective study Cancer. 1981 47 1336 1343 Search in Google Scholar

Waloryszak B, Makowska W. The significance of the cytological evaluation in the early diagnosis of the laryngeal carcinoma. Polish Otolaryngol. 1994; 48: 331–334. WaloryszakB MakowskaW The significance of the cytological evaluation in the early diagnosis of the laryngeal carcinoma Polish Otolaryngol. 1994 48 331 334 Search in Google Scholar

Malamou-Mitsi VD, Assimakopoulos DA, Goussia A, Pappa L, Skevas AT. Agnantis N.J. Contribution of exfoliative cytology to the diagnosis of laryngeal lesions. Acta Cytol. 2000; 44: 993–999. Malamou-MitsiVD AssimakopoulosDA GoussiaA PappaL SkevasAT AgnantisN.J. Contribution of exfoliative cytology to the diagnosis of laryngeal lesions Acta Cytol. 2000 44 993 999 Search in Google Scholar

Gugatschka M, Kiesler K, Beham A, Rechenmacher J, Friedrich G. Hyperplastic epithelial lesions of the vocal folds: Combined use of exfoliative cytology and laryngostroboscopy in differential diagnosis. Eur Arch Otorhinolaryngol. 2008; 265: 797–801. GugatschkaM KieslerK BehamA RechenmacherJ FriedrichG Hyperplastic epithelial lesions of the vocal folds: Combined use of exfoliative cytology and laryngostroboscopy in differential diagnosis Eur Arch Otorhinolaryngol. 2008 265 797 801 Search in Google Scholar

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