Next Article in Journal
Assessing Fat Grafting in Breast Surgery: A Narrative Review of Evaluation Techniques
Previous Article in Journal
Amyloids and the Heart: An Update
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
JCM
Volume 13
Issue 23
10.3390/jcm13237208
jcm-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

History of Breast Cancer in Patients with Oral Lichen Planus: A Case–Control Study

by
María García-Pola
1,*,
Lucía Rodríguez-Fonseca
1,
Claudia Llorente-Álvarez
2 and
Santiago Llorente-Pendás
3
1
Department of Surgery and Medical-Surgical Specialties, Faculty of Medicine and Sciences of the Health, Oviedo University, 33006 Oviedo, Spain
2
Hospital Rio Hortega, 47012 Valladolid, Spain
3
Private Practice, 33004 Oviedo, Spain
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2024, 13(23), 7208; https://doi.org/10.3390/jcm13237208
Submission received: 1 November 2024 / Revised: 21 November 2024 / Accepted: 24 November 2024 / Published: 27 November 2024
(This article belongs to the Section Epidemiology & Public Health)
Browse Figure
Versions Notes

Abstract

:
Objectives: The purpose of this study was to determine the association between oral lichen planus (OLP) and the history of cancer outside of oral cavity and the predominance of its location. Methods: This case–control study included 600 OLP patients and 600 control subjects evaluated in the same section, matched for age and sex to the OLP patients. OLP patients were diagnosed clinically and histologically. Initially, the prevalence of the most frequent types of cancers was described. A Pearson chi-squared test model was used to determine the association of cancer history and OLP. It was considered statistically significant whether p value was ≤0.05. The final multivariate regression model was built after applying a backward selection method to the complete multivariate model considering the odds ratio (OR) with a 95% confidence interval (CI). Results: The history of cancer was significantly associated with OLP regardless of age, sex, tobacco and or alcohol use in both univariate [OR = 2.26 (95%CI: 1.26–4.24); p = 0.008] and multivariate analyses [OR = 2.21 (95%CI: 1.21–4.19); p = 0.012]. According to the location of cancer, there was an association between OLP and history of breast cancer [OR = 3.71 (95%CI = 1.03–13.38); p = 0.032]. Conclusions: This case–control study suggests a higher frequency of cancer, particularly breast cancer, among patients with OLP compared to the control group. Due to the study’s design and sample limitations, these findings should be interpreted cautiously. Future longitudinal, multi-institutional studies with rigorous control for cancer history and other confounding factors are essential to further explore the association between OLP and cancer, particularly breast cancer.

1. Introduction

Oral lichen planus (OLP) is considered as a chronic inflammatory disorder and its global prevalence is estimated at 1.01% [1]. OLP mostly occurs in middle-aged individuals and is more common in women. OLP is an oral potentially malignant disorder [2] with a pooled proportion of malignant transformation of 1.43% [3].
Despite past and recent research, the pathogenesis of OLP remains unknown, where T cells play a relevant role in managing immune response [4]. OLP is not an infectious disease, but it has been considered that some antigens that present primarily to Langerhans cells may come from the oral microbiota [5]. It has also been linked to genetic factors and to an association with the hepatitis C virus, systemic psychosomatic disorders, or to endocrine, cardiovascular and autoimmune diseases [6].
The antigens involved in the pathogenesis of OLP trigger the start of T-cell proliferation and immune response against basal epithelial cells [7]. Physiologically, these basal epithelial cells suffer from apoptosis by the disruption of their basement membrane and the lamina propria, with intra- and subepithelial T-lymphocyte infiltration [8].
In the pathogenesis of OLP, T cells intervene through pro-inflammation and the suppression of inflammation [9]. The attraction of other cells as well as the secretion of molecules such as cytokines and chemokines will favor the progression or regression of the disease [8,10,11].
Chronic inflammation at the expense of cytokines could favor cell proliferation and its progression to oral squamous cell carcinoma (OSCC) [12]. Inflammation has also been described as one possible route for the pathogenesis of other types of cancer [13]. In this process, pro-inflammatory mediators act by stimulating inflammation to either slow or stop tumor progression or to facilitate tumor growth and metastasis [14]. Furthermore, the increase in proteins, such as CXCL13, that promote inflammation and genes related to Th-17 cell differentiation have been identified in OLP patients, in OSCC [15] and in other carcinomas, such as breast [16,17], colorectal [18], bladder [19] and cutaneous melanoma [20].
When questioning the patient with OLP regarding their medical history, it is not very common to include investigations on their history of having suffered cancer outside the oral cavity. Thus, questions are collected about whether the patient has suffered from “previous malignant diseases” [21], “neoplastic diseases” [22,23], “disease of cancer” [24], “non-oral malignancy” [25] or “comorbidities of neoplastic pathologies” [26].
The prevalence of cancer history in OLP patients has been reported in some research, providing percentages in a general way that refer to “any type of cancer” in the global population, or specifying by pointing out the exact location outside the oral cavity. Thus, it has been pointed out that the rate of oropharyngeal cancers can rise from 0 [27] up to 22.5% in oral locations [28]. Variations in the prevalence of cancer history within the same country have also been expressed, such as in Italy, from 2.4% [23] to 21% [29], or in Sweden, from 0.4% [30] to 4.76% [31].
The types of cancer in patients with OLP include colon (2.6%) [28], skin (3.8%) [28], head–neck–face (3.8%) [28], hematological (1.9%) [28], hepatic (10.1%) [32] or thyroid, from 1.2% [28] to 5.8% [33]. In OLP patients, it has also been noted that prostate cancer represents 0.7% [31] or 0.8% out of all malignancies [28]; however, among men, it is between 2.27% [31] and 2.63% [28]. Breast cancer prevalence varies from 0.9% [34] to 7.1% [18] among all cancers, and among women, it can represent up to 9.3% [28].
Methodologically, the research mentioned in the previous paragraph belongs to studies with a small sample size, cohort [22,24,29] or case–control studies [21,26,28]. In other studies, even though they contain large samples of OLP, they are not compared with control groups [23,31].
Because of this variability about the registration of the prevalence of the history of cancer in OLP and the possibility of history of cancer to act as a risk of suffering from lichen planus, we consider the need to carry out a case–control study. Therefore, the purpose of the present study was to survey the link between OLP patients and a history of cancer through a case–control study, to ascertain the relationship between history of cancer and OLP with the following research question: “Is a history of cancer outside of the oral cavity associated with the risk of suffering from Oral Lichen Planus?”.

2. Materials and Methods

The methodological design was a retrospective case–control study planned according to the Strengthening Reporting of Observational Studies in Epidemiology (STROBE) guidelines (Table S1) [35].

2.1. Subjects

The experimental group consisted of 600 OLP patients cared for in the Oral Medicine Section at Oviedo University, between January 2014 and December 2023. The study was approved by the Ethics Committee of the Principality of Asturias and complied with the requirements of the Declaration of Helsinki (nº 127/13 and nº 140/23).
The sample size was limited to a 10-year period without considering a specific number of subjects. Thus, the inclusion of patients was consecutive and without prior selection to reduce the risk of selection bias. The criteria for inclusion in the case group was for patients to be at least 18 years old and to have a diagnosis of OLP appraised clinically and histologically according to the WHO criteria [36] with subsequent modifications [37], and as described in our previous research [38]. Therefore, inclusion criteria for clinical diagnosis of OLP were contemplated according to the following criteria: lesions with gray-white lines or papular pattern and by atrophic, erosive, bullous and/or plaque variety lesions of a two-sided disposition. Histopathological criteria included the following: (1) “liquefactive degeneration” in the basal layer; (2) a band-like zone of cellular infiltration limited to the top part of the lamina propria; and (3) an absence of epithelial dysplasia [37].
The control group consisted of 600 consecutive patients matched for age and sex to the OLP patients (Figure 1). The subjects of the control group were selected consecutively until completing the same number of patients with the same age and sex corresponding to the OLP group. They were evaluated in the same section over the same interval of time for other types of benign oral mucous diseases, without any signs or previous history of OLP (N = 340), or for examination and checkup of the oral cavity (N = 260) (Figure 1). We considered benign oral mucous diseases, traumatic lesions, oral non-pathological lesions and lesions treated with excisional biopsy such as mucoceles, diapneusia, epulis fissuratum, fibroepithelial hyperplasia or other connective tissue, squamous papilloma and lipomas. Oral non-pathological lesions were included following the criteria of Tortorici et al.: Fordyce granules; coated tongue; and hairy tongue [39].
The exclusion criteria of the case group were subjects under 18 years old, either pregnant or breastfeeding, presenting oral lichenoid reaction or oral cancer in addition to the OLP on the day of the first visit, or patients who had undergone radiotherapy or taken anti-cancer drugs over the previous months. Diagnosis lichenoid reaction was considered based on the criteria by Aguirre et al. [40]. Patients with OLP outside the oral cavity were not excluded.

2.2. Protocol

The protocol included recording patients’ sex, age, and tobacco and alcohol consumption. The smoker variable was divided into 5 categories: non-smoker, with never having smoked; smoking habit with ≤10 cigarettes; smoking habit with more than 10 cigarettes [30,41]; other forms of smoking (such as cigar, pipe or another); and former smoker, where the patients had stopped smoking at least 6 months before interview [42]. We considered unit of alcohol as follows: 1 glass of wine, ¼ liter of beer, or another measure of liqueur [41,43]. Therefore, the drinker variable was divided into 4 categories: non-drinker (never); consumption of up to two units per day; consumption of more than two units; and weekend drinker [41,43,44].
Clinical findings included the form of OLP (atrophic-erosive and non-atrophic-erosive), number of locations, medical history, and prescription medication. The number of oral locations recorded was two, consistent with the bilateral definition [36,37], or more [38]. Before performing the incisional biopsy on the first visit, all patients were interrogated about their history of cancer treatment or prior diagnoses of cancer, providing where necessary the document of their clinical report.
Data collection was always carried out by the first author, accompanied at certain times by the co-authors, following the usual protocol for clinical history, anamnesis, and examination.

2.3. Statistical Analysis

Statistical analysis was performed using R-core (R Development Core Team, version 4.1.3). Initially, a descriptive study was made of each variable. Due to the mean age of the patients registered, the dichotomous cut-off point was split into two categories: 60 years old or under, and over 60. Tobacco and alcohol consumption were divided, respectively, into the 5 and 4 categories considered previously. The clinical form was distributed based on non-atrophic-erosive and atrophic-erosive following the criteria of Carbone et al. [23] and our previous study [38]. The number of OLP locations was divided into two locations (bilateral by definition) [37], and three or more locations [38]. Pearson’s Chi2 test and Fisher test were used to compare categorical parameters between the groups. p values below 0.05 were considered statistically significant. Logistic regression models were used to measure the association of OLP and history of cancer. Given the different types of cancer according to sex, and that age > 60 years, tobacco use, and alcohol intake are considered risk factors for several cancers, these variables were considered in the multivariate analysis [45] to estimate the odds ratios (ORs) and their 95% confidence intervals (95% CIs). The final multivariate regression model was built after applying a backward selection method to the complete multivariate model. The Akaike information criterion (AIC) was used to measure the quality of the stepwise regression model.

3. Results

3.1. Descriptive Analysis

3.1.1. Age and Sex

From a sample of 1200, the OLP patients and the control group each consisted of 443 women (73.8%) and 157 men (26.2%) (Table 1). The age fluctuated from 18 to 90 years old, with a mean age of 59.58 (±12.47). At the time of the first visit, the mean age of the women was 60.59 (range 18–90) and the mean age of the men was 56.71 (range 18–86).

3.1.2. Tobacco Use and Alcohol Drinker

There were fewer smokers and more ex-smokers in the OLP group than in the control group (11.2% vs. 24% and 14.8% vs. 13.5%, respectively).
Regarding alcohol consumption, when comparing the two groups, there were more patients among the OLP group who drank more than 2 units per day (8.9% vs. 7.2%), and the control group had a higher number of patients who were weekend drinkers (10.4% vs. 4%).

3.1.3. Clinical Number of Oral Locations of OLP and Clinical Form of OLP

Three hundred and twelve OLP patients (52.0%) had two locations of OLP and three hundred and sixty-eight (61.3%) of OLP patients presented the atrophic-erosive clinical form (Table 1).

3.1.4. Prevalence of History of Cancer and Types of Cancer

A total of 35 OLP patients had a history of cancer (5.8%), compared to 16 in the control group (2.7%). The demographic characteristics of patients with a history of cancer in the OLP and the control group are shown in Table 2. Forty-two of them were women, twenty-nine (69.07%) and thirteen (81.25%) for each group, respectively. The mean age of the OLP patients with a history of cancer was 62.13 (35 to 81), whereas in the control group, it was 61 (43 to 75).
The clinical form of OLP with history of cancer was atrophic-erosive in 25 patients (71.42%) and 19 patients presented 3 or more locations (54.3%).
OLP patients had been diagnosed with cancers in fourteen locations, with the most common cancers in the OLP patients being breast cancer (1.83%) and cancer of the cervix (1.16%). In the control group, the two most common cancers were breast and basal cell carcinoma (0.5%). One patient in each group reported a history of cancer in two locations. The types of cancer and demographic characteristics according to age and sex are reflected in Table 3.

3.2. Results of the Univariate and Multivariate Analyses

According to the type of cancer, there were statistically significant differences between the OLP patients’ group and the control group for breast cancer with OR = 3.71, CI = 1.03–13.38; p = 0.032. Despite the higher prevalence of cervix cancer and colon cancer among the OLP patients, they did not show statistically significant differences (p = 0.094 and p = 0.317, respectively).
The results of the univariate and multivariate analyses of history of cancer are presented in Table 4. The crude OR associated was 2.26 [95% confidence interval (CI) 1.26–4.24; p =0.008], and the multivariate after applying a backward selection showed an association (OR = 2.21, CI = 1.21–4.19; p = 0.012). Age, gender, smoking and alcoholic habits are not predictive variables in the relationship between cancer history and OLP patients. The difference in the values recorded when using AIC was minimal in the different steps when introducing the variables of sex, age, tobacco and alcohol (Table 5).

4. Discussion

The results of the present observational study suggest a link between OLP and a history of cancer outside the oral cavity. Our case–control study showed that OLP patients were twice as likely to have a history of cancer than subjects without OLP (OR: 2.21). We have described a heterogeneous sample in the types of cancer as did Dave et al. [28] and Rödström et al. [31].
The sample of OLP patients follows the most frequently recorded characteristics of OLP, i.e., a higher frequency among women [46,47,48,49] and an age approaching 60 years, as recorded in previous studies [50,51,52].
Regardless of the number of cigarettes per day, there were more smokers in the control group when compared to OLP patients in a statistically significant way. These findings corroborate previous studies [21,53,54] and contradict others [26,55,56].
In our sample of patients with OLP, there were fewer subjects who drank in a statistically significant manner. Pippi et al. stated that when the variable of smoker and drinker was considered together, it was higher in patients with OLP than in the control group [57]. Other studies have shown that there are no differences between the alcohol habits of patients with OLP and the control group [32,54,56].
The main objective of this research was to provide the prevalence of cancer history in patients with OLP, showing a prevalence of 5.8%, which contrasts with the control group of 2.7%. It is understood that this epidemiological study cannot prove that cancer history and OLP are causally related, nor that OLP patients are more susceptible to presenting cancer outside the oral cavity, but it does clarify their association.
Two decades ago, Rödström et al. described a prevalence of 4.76% of history of cancer in a sample of 1080 Swedish patients with OLP, from the city of Göteborg; however, these data were lower than those expected on the incidence of cancer in the general population [31]. In the same city, in 2011, a lower prevalence of cancer history, of 0.4%, was observed among OLP patients, while in the general population, it was 3.4% [30]. These figures contrast with those provided by Burkhart et al. [58] on a sample of North Americans in 1996, who recorded 16%, and more recently, in 2023, the prevalence reached up to 22.5% [28], thus observing an increase in prevalence with data subtracted from a database.
Other figures on OLP prevalence were published in a comparative study on the characteristics of OLP in Croatian and Australian patients, with history of cancer recorded at 3.7% in the first and 17.8% in the latter country [59], which shows a geographical discrepancy. Another example is from Israel, where a history of cancer was recorded in 14.9% of a sample of 171 OLPs [25].
The prevalence of history of cancer in OLP patients also varies widely within the same country; for example, in Turin, Italy, a rate of 2.47% was registered [23]; in Brescia, 5.6% [22] (a percentage very similar to that recorded in the present study (5.8%)); in Catanzaro, it was 7.9% [26]; and in Rome, it was 21% [29]. Geographically, the highest prevalence of a history of cancer in patients with OLP has been recorded in the United States [28,58], Brisbane (Australia) [59] and the aforementioned Italian city of Rome [29].
Certain factors are recognized that may affect the incidence of cancer, highlighting that the type of cancer is dependent on age > 60 years, sex, tobacco and alcohol [45]. By considering the sex of the patients, the present study confirmed the figures on the prevalence of cancer proposed by the research of a cohort of 808 patients from Northern Italy [23]. In both studies, the absence of prostate cancer was found among men with OLP, while in both genders, the prevalence of breast cancer among women with OLP was exactly 2.4% (12 breast cancer among 493 Italian women and 11 among Spanish women). In addition, our study contributed an OR of 3.7 when compared with patients without OLP. These figures contrast with the reported percentage of breast cancer patients with OLP of 9.3% in North America, the high-income country with the highest incidence of breast cancer [60].
On the contrary, we did not find an association of cancer history in OLP patients with risk factors associated with sex, age over 60 years, smokers and drinkers. These findings may be in agreement with the reflection that patients over 60 years of age do not have a higher incidence of cancer than in young people based on the mentioned factors [45].
Other factors that could be involved in the association of cancer history and OLP that justify the geographical discrepancies are related to genetic factors, lifestyle, and comorbid diseases such as viral, or immunological diseases [45,61]. Upon analyzing the types of cancers associated with OLP, there are genetic and non-genetic factors for breast cancer [62]; among the latter, excess body weight stands out [63]. Adamo et al. showed that body mass index was higher in OLP patients than in the control group in a statistically significant way [64]; however, in a later study, they observed that keratotic forms of OLP did not present this association [21].
Regarding viral diseases, the risk of a history of liver disease in OLP patients may also be due to geographical and pathogenic factors through its link with hepatitis C virus (HCV) [65]. We presented one case of a history of hepatocellular carcinoma in an OLP patient, with a figure much lower than those presented in a Japanese population [32]. The study by Nagao et al. [32] took place in Japan, and the authors highlighted that the study was carried out in a city whose residents had a high prevalence of HCV infection. These authors reported 8 hepatic carcinomas in a sample of 59 patients (13.5%), while in the control group of 85 subjects, they observed 2 cases of hepatic cancer (2.35%) [32]. On the contrary, they showed that other extrahepatic carcinomas were more frequent in the control group than in the OLP group (11.76% vs. 8.47%) [32]. This HCV association with cancer would justify the involvement of more pathogenic factors related to cancer than those mentioned as major ones depending on the location. Although the main cause of hepatocellular carcinoma in some countries such as Japan and the United States is HCV [66], recent studies have indicated that the incidence of hepatitis C-related liver cancer is decreasing [67,68].
Another carcinoma related to OLP was thyroid cancer, being geographically more evident in prevalence in Taiwan (1.88%) [33], the United States (1.28%) [28] and Spain (0.33%). Comorbidity with thyroid pathology has been observed in patients with OLP, reflecting its autoimmune basis [69], non-immune inflammatory processes [70], and raising the question of whether the comorbidity could be due to genetic susceptibility. Thyroid cancer is also associated with obesity and dyslipidemia and other cardiovascular risk factors [71]. However, a recent systematic review has shown that patients with OLP have higher levels of total cholesterol and lower high-density lipoprotein than the control group, but no other parameters in particular, which makes it difficult to interpret the link between thyroid cancer, dyslipidemia and OLP [72].
A type of tumor present in our sample was thymoma. The recent literature indicates the possible association between thymoma in isolation [73,74] or as part of Good’s syndrome [75], drawing attention to the thought of a thymoma in the face of erosive OLP.
The possible link between a history of cancer and LP is complicated to explain. In OLP, there is an immune response of Th-1, Th-9 and Th-17 lymphocytes with an imbalance of Th-2 and subsequently an increased cytokine release [7,76]. Cytokines produced by inflammatory Th-17 cells stimulate inflammation-dependent tumor growth by promoting angiogenesis and suppressing antitumor immunity [77], a condition that has been described in skin [78], breast [79,80] and papillary thyroid carcinoma tumors [81]. However, recently, Chen et al. observed a negative evaluation between the expression of IL-17 levels during the pathogenesis of OLP and determined an aberrant expression of fibroblast growth factor 21 (FGF21), a protein also related to autoimmune diseases (ADs) [82]. Other studies have indicated that some ADs such as Sjogren’s syndrome or lupus erythematous may act as protective factors against breast cancer risk [83].
In a systematic review that analyzed the malignancy of OLP, it was revealed that the history of cancer could not be adequately included due to a lack of information in the studies selected for analysis [84]. The present study is the starting point to emphasize the variable history of cancer among patients with OLP. Considering the fact that OLP is a potentially malignant disorder, clinicians will benefit from being aware of this link, which also suggests the benefits of oral screening for OLP in women with breast cancer.
The present study has some limitations. Methodologically, the main limitation of this case–control study is related to the fact that the control group belongs to subjects from the same unit as patients with OLP, even though we selected a control group matched by sex and age and carried out our study with a large sample. In this sense, the methodological criticism of case–control studies developed by Seyghan et al. [85] is proven, as the authors argue that not even the control group from the general population can be valid, since people from the general population could possibly have a lower prevalence of the pathology under study—in this case, cancer. In addition, to mitigate confounding factors, a multivariate logistic regression was performed [86,87].
Despite including the most representative risk factors for oral cancer, there are others such as economic income, healthcare or even diet, which could be included in future studies.
The study was conducted in a single center and using controls from the same section without OLP, so we suggest new multicenter studies with general population controls to reduce prevalence biases as well as prospective cohort studies that collaborate in the deepening of this topic. Another limitation is that the ranges of the confidence intervals recorded for the association between cancer history and particularly breast cancer are close to the null value, so they do not show a solid robustness even though the association findings are statistically significant. Therefore, these results should be interpreted with caution, suggesting new studies, ideally prospective, to confirm the possible association of OPL and cancer history.

5. Conclusions

This case–control study suggests a higher frequency of cancer, particularly breast cancer, among patients with OLP compared to the control group. Due to the study’s design and sample limitations, these findings should be interpreted cautiously. Future longitudinal, multi-institutional studies with rigorous control for cancer history and other confounding factors are essential to further explore the association between OLP and cancer, particularly breast cancer.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/jcm13237208/s1, Table S1: STROBE statement—checklist of items that should be included in reports of case–control studies.

Author Contributions

Conceptualization, M.G.-P., S.L.-P., C.L.-Á. and L.R.-F.; methodology, M.G.-P., C.L.-Á. and L.R.-F.; software, M.G.-P. and L.R.-F.; validation, M.G.-P., C.L.-Á., S.L.-P. and L.R.-F.; formal analysis, M.G.-P. and L.R.-F.; investigation, M.G.-P., C.L.-Á., S.L.-P. and L.R.-F.; resources, M.G.-P. and L.R.-F.; data curation, M.G.-P., C.L.-Á., S.L.-P. and L.R.-F.; writing—original draft preparation, M.G.-P., C.L.-Á., S.L.-P. and L.R.-F.; writing—review and editing, M.G.-P., S.L.-P., C.L.-Á. and L.R.-F.; visualization, M.G.-P., C.L.-Á., S.L.-P. and L.R.-F.; supervision, M.G.-P., C.L-Á., S.L.-P. and L.R.-F. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Principality of Asturias, nº 127/13 (approval on 16 December 2013) and nº 140/23 (ambispective study, approval on 21 April 2023).

Informed Consent Statement

Informed consent was obtained from all subjects involved in the study.

Data Availability Statement

The data presented in this study are available upon request from the corresponding author.

Acknowledgments

The authors thank Tania Iglesias Cabo, from Statistics Consulting Unit of the University of Oviedo, who performed the statistical analysis.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. González-Moles, M.Á.; Warnakulasuriya, S.; González-Ruiz, I.; González-Ruiz, L.; Ayén, Á.; Lenouvel, D.; Lenouvel, D.; Ruiz-Ávila, I.; Ramos-García, P. Worldwide prevalence of oral lichen planus: A systematic review and meta-analysis. Oral Dis. 2021, 27, 813–828. [Google Scholar] [CrossRef] [PubMed]
  2. Warnakulasuriya, S.; Kujan, O.; Aguirre-Urizar, J.M.; Bagan, J.V.; González-Moles, M.Á.; Kerr, A.R.; Lodi, G.; Mello, F.W.; Monteiro, L.; Ogden, G.R.; et al. Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer. Oral Dis. 2021, 27, 1862–1880. [Google Scholar] [CrossRef] [PubMed]
  3. González-Moles, M.Á.; Ramos-García, P. An Evidence-Based Update on the Potential for Malignancy of Oral Lichen Planus and Related Conditions: A Systematic Review and Meta-Analysis. Cancers 2024, 16, 608. [Google Scholar] [CrossRef]
  4. Bao, C.F.; Wang, F.; Zhou, D.Y.; Zhou, G. CD4+CD8αα+ is the dominant phenotype of intraepithelial lymphocytes and regulated by ThPOK and Runx3 in oral lichen planus. J. Oral Pathol. Med. 2024, 53, 480–490. [Google Scholar] [CrossRef]
  5. DeAngelis, L.M.; Cirillo, N.; McCullough, M.J. The immunopathogenesis of oral lichen planus-Is there a role for mucosal associated invariant T cells? J. Oral Pathol. Med. 2019, 48, 552–559. [Google Scholar] [CrossRef]
  6. Liu, W.; Deng, Y.; Shi, H.; Shen, X. Clinical investigation on oral lichen planus and associated comorbidities needs a holistic concept. Oral Dis. 2023, 29, 327–329. [Google Scholar] [CrossRef] [PubMed]
  7. Deng, X.; Wang, Y.; Jiang, L.; Li, J.; Chen, Q. Updates on immunological mechanistic insights and targeting of the oral lichen planus microenvironment. Front. Immunol. 2023, 13, 1023213. [Google Scholar] [CrossRef]
  8. Roopashree, M.R.; Gondhalekar, R.V.; Shashikanth, M.C.; George, J.; Thippeswamy, S.H.; Shukla, A. Pathogenesis of oral lichen planus—A review. J. Oral Pathol. Med. 2010, 39, 729–734. [Google Scholar] [CrossRef]
  9. El-Howati, A.; Thornhill, M.H.; Colley, H.E.; Murdoch, C. Immune mechanisms in oral lichen planus. Oral Dis. 2023, 29, 1400–1415. [Google Scholar] [CrossRef]
  10. Lavanya, N.; Jayanthi, P.; Rao, U.K.; Ranganathan, K. Oral lichen planus: An update on pathogenesis and treatment. J. Oral Maxillofac. Pathol. 2011, 15, 127–132. [Google Scholar] [CrossRef]
  11. Kurago, Z.B. Etiology and pathogenesis of oral lichen planus: An overview. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2016, 122, 72–80. [Google Scholar] [CrossRef]
  12. Ghazi, N.; Khorasanchi, M. Markers associated with malignant transformation of oral lichen planus: A review article. Arch. Oral Biol. 2021, 127, 105158. [Google Scholar] [CrossRef] [PubMed]
  13. Fernandes, Q.; Inchakalody, V.P.; Bedhiafi, T.; Mestiri, S.; Taib, N.; Uddin, S.; Merhi, M.; Dermime, S. Chronic inflammation and cancer; the two sides of a coin. Life Sci. 2023, 338, 122390. [Google Scholar] [CrossRef] [PubMed]
  14. Niklander, S.E. Inflammatory Mediators in Oral Cancer: Pathogenic Mechanisms and Diagnostic Potential. Front. Oral Health 2021, 2, 642238. [Google Scholar] [CrossRef] [PubMed]
  15. de Lanna, C.A.; da Silva, B.N.M.; de Melo, A.C.; Bonamino, M.H.; Alves, L.D.B.; Pinto, L.F.R.; Cardoso, A.S.; Antunes, H.S.; Boroni, M.; Cohen Goldemberg, D. Oral Lichen Planus and Oral Squamous Cell Carcinoma share key oncogenic signatures. Sci. Rep. 2022, 12, 20645. [Google Scholar] [CrossRef] [PubMed]
  16. Jiang, L.; Wang, D.; Sheng, M.; Tong, D.; Liu, H.; Dong, L.; Ma, J. CXCL13/CXCR5 are potential biomarkers for diagnosis and prognosis for breast cancer. Age 2020, 31, 70. [Google Scholar]
  17. Cao, Y.; Guan, L.; Yang, L.; Wei, C. PANoptosis-related molecular clustering and prognostic signature associated with the immune landscape and therapy response in breast cancer. Medicine 2024, 103, e39511. [Google Scholar] [CrossRef]
  18. Cabrero-de Las Heras, S.; Hernández-Yagüe, X.; González, A.; Losa, F.; Soler, G.; Bugés, C.; Baraibar, I.; Esteve, A.; Pardo-Cea, M.Á.; Ree, A.H.; et al. Changes In Serum CXCL13 Levels Are Associated With Outcomes of Colorectal Cancer Patients Undergoing First-Line Oxaliplatin-Based Treatment. Biomed. Pharmacother. 2024, 176, 116857. [Google Scholar] [CrossRef]
  19. Sun, X.; Chen, Q.; Zhang, L.; Chen, J.; Zhang, X. Exploration of prognostic biomarkers and therapeutic targets in the microenvironment of bladder cancer based on CXC chemokines. Math. Biosci. Eng. 2021, 18, 6262–6287. [Google Scholar] [CrossRef]
  20. Si, Z.; Hu, H. Identification of CXCL13 as an Immune-Related Biomarker Associated with Tumorigenesis and Prognosis in Cutaneous Melanoma Patients. Med. Sci. Monit. 2021, 27, e932052. [Google Scholar] [CrossRef]
  21. Adamo, D.; Calabria, E.; Canfora, F.; Coppola, N.; Leuci, S.; Mignogna, M.; Muzio, L.L.; Spirito, F.; Giuliani, M.; Azzi, L.; et al. SIPMO (Italian Society of Oral Pathology, Medicine). Anxiety and depression in keratotic oral lichen planus: A multicentric study from the SIPMO. Clin. Oral Investig. 2023, 27, 3057–3069. [Google Scholar] [CrossRef] [PubMed]
  22. Bardellini, E.; Amadori, F.; Flocchini, P.; Bonadeo, S.; Majorana, A. Clinicopathological features and malignant transformation of oral lichen planus: A 12-years retrospective study. Acta Odontol. Scand. 2013, 71, 834–840. [Google Scholar] [CrossRef]
  23. Carbone, M.; Arduino, P.G.; Carrozzo, M.; Gandolfo, S.; Argiolas, M.R.; Bertolusso, G.; Conrotto, D.; Pentenero, M.; Broccoletti, R. Course of oral lichen planus: A retrospective study of 808 northern Italian patients. Oral Dis. 2009, 15, 235–243. [Google Scholar] [CrossRef]
  24. Bombeccari, G.P.; Tettamanti, M.; Pallotti, F.; Spadari, F.; Giannì, A.B. Exacerbations of oral lichen planus and elevated levels of aminotransferases. Int. J. Dermatol. 2017, 56, 842–849. [Google Scholar] [CrossRef]
  25. Kaplan, I.; Ventura-Sharabi, Y.; Gal, G.; Calderon, S.; Anavi, Y. The dynamics of oral lichen planus: A retrospective clinicopathological study. Head Neck Pathol. 2012, 6, 178–183. [Google Scholar] [CrossRef] [PubMed]
  26. Piloni, S.; Ferragina, F.; Barca, I.; Kallaverja, E.; Cristofaro, M.G. The Correlation between Oral Lichen Planus and Thyroid Pathologies: A Retrospective Study in a Sample of Italian Population. Eur. J. Dent. 2024, 18, 510–516. [Google Scholar] [CrossRef]
  27. Gandolfo, S.; Richiardi, L.; Carrozzo, M.; Broccoletti, R.; Carbone, M.; Pagano, M.; Vestita, C.; Rosso, S.; Merletti, F. Risk of oral squamous cell carcinoma in 402 patients with oral lichen planus: A follow-up study in an Italian population. Oral Oncol. 2004, 40, 77–83. [Google Scholar] [CrossRef]
  28. Dave, A.; Shariff, J.; Philipone, E. Association between oral lichen planus and systemic conditions and medications: Case-control study. Oral Dis. 2021, 27, 515–524. [Google Scholar] [CrossRef]
  29. Tenore, G.; Mohsen, A.; Rocchetti, F.; Rossi, G.; Cassoni, A.; Battisti, A.; Della Monaca, M.; Di Gioia, C.R.T.; De Felice, F.; Botticelli, A.; et al. Risk of Oral Squamous Cell Carcinoma in One Hundred Patients with Oral Lichen Planus: A Follow-Up Study of Umberto I University Hospital of Rome. Cancers 2023, 15, 3004. [Google Scholar] [CrossRef]
  30. Robledo-Sierra, J.; Mattsson, U.; Jontell, M. Use of systemic medication in patients with oral lichen planus- a possible association with hypothyroidism. Oral Dis. 2013, 19, 313–319. [Google Scholar] [CrossRef]
  31. Rödström, P.O.; Jontell, M.; Mattsson, U.; Holmberg, E. Cancer and oral lichen planus in a Swedish population. Oral Oncol. 2004, 40, 131–138. [Google Scholar] [CrossRef] [PubMed]
  32. Nagao, Y.; Sata, M. A retrospective case-control study of hepatitis C virus infection and oral lichen planus in Japan: Association study with mutations in the core and NS5A region of hepatitis C virus. BMC Gastroenterol. 2012, 12, 31. [Google Scholar] [CrossRef]
  33. Tang, Y.; Shi, L.; Jiang, B.; Zhou, Z.; Shen, X.A. Cross-Sectional Study of Oral Lichen Planus Associated With Thyroid Diseases in East China. Front. Endocrinol. 2020, 10, 928. [Google Scholar] [CrossRef]
  34. Yao, H.; Deng, Y.; Du, G.; Wang, Y.; Tang, G. Elevated mean platelet volume in oral lichen planus and increased blood urea nitrogen level in its red-form: An observational study. BMC Oral Health 2021, 21, 310. [Google Scholar] [CrossRef]
  35. Vandenbroucke, J.P.; von Elm, E.; Altman, D.G.; Gøtzsche, P.C.; Mulrow, C.D.; Pocock, S.J.; Poole, C.; Schlesselman, J.J.; Egger, M.; STROBE Initiative. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): Explanation and elaboration. Epidemiology 2007, 18, 805–835. [Google Scholar] [CrossRef]
  36. Kramer, I.R.; Pindborg, J.J.; Bezroukov, V.; Infirri, J.S. Guide to epidemiology and diagnosis of oral mucosal diseases and conditions. Community Dent. Oral Epidemiol. 1980, 8, 1–26. [Google Scholar] [PubMed]
  37. van der Meij, E.H.; van der Waal, I. Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications. J. Oral Pathol. Med. 2003, 32, 507–512. [Google Scholar] [CrossRef] [PubMed]
  38. Rodríguez-Fonseca, L.; Llorente-Pendás, S.; García-Pola, M. Risk of Prediabetes and Diabetes in Oral Lichen Planus: A Case-Control Study according to Current Diagnostic Criteria. Diagnostics 2023, 13, 1586. [Google Scholar] [CrossRef] [PubMed]
  39. Tortorici, S.; Corrao, S.; Natoli, G.; Difalco, P. Prevalence and distribution of oral mucosal non-malignant lesions in the western Sicilian population. Minerva Stomatol. 2016, 65, 191–206. [Google Scholar]
  40. Aguirre-Urizar, J.M.; Alberdi-Navarro, J.; Lafuente-Ibáñez de Mendoza, I.; Marichalar-Mendia, X.; Martínez-Revilla, B.; Parra-Pérez, C.; Juan-Galíndez, A.D.; Echebarria-Goicouria, M.Á. Clinicopathological and prognostic characterization of oral lichenoid disease and its main subtypes: A series of 384 cases. Med. Oral Patol. Oral Cir. Bucal 2020, 25, e554–e562. [Google Scholar] [CrossRef]
  41. Pentenero, M.; Broccoletti, R.; Carbone, M.; Conrotto, D.; Gandolfo, S. The prevalence of oral mucosal lesions in adults from the Turin area. Oral Dis. 2008, 14, 356–366. [Google Scholar] [CrossRef] [PubMed]
  42. Feng, J.; Zhou, Z.; Shen, X.; Wang, Y.; Shi, L.; Wang, Y.; Hu, Y.; Sun, H.; Liu, W. Prevalence and distribution of oral mucosal lesions: A cross-sectional study in Shanghai, China. J. Oral Pathol. Med. 2015, 44, 490–494. [Google Scholar] [CrossRef] [PubMed]
  43. Cortés, S.B.; Zarceño, C.S.; de la Orden, S.G. Methodology for the estimation of use of tobacco, alcohol and other drugs. Nutr. Hosp. 2015, 31 (Suppl. 3), 257–264. [Google Scholar] [CrossRef]
  44. Moreno-López, L.A.; Esparza-Gómez, G.C.; González-Navarro, A.; Cerero-Lapiedra, R.; González-Hernández, M.J.; Domínguez-Rojas, V. Risk of oral cancer associated with tobacco smoking, alcohol consumption and oral hygiene: A case-control study in Madrid, Spain. Oral Oncol. 2000, 36, 170–174. [Google Scholar] [CrossRef]
  45. Li, L.; Shan, T.; Zhang, D.; Ma, F. Nowcasting and forecasting global aging and cancer burden: Analysis of data from the GLOBOCAN and Global Burden of Disease Study. J. Natl. Cancer Cent. 2024, 4, 223–232. [Google Scholar] [CrossRef] [PubMed]
  46. Xue, J.L.; Fan, M.W.; Wang, S.Z.; Chen, X.M.; Li, Y.; Wang, L. A clinical study of 674 patients with oral lichen planus in China. J. Oral Pathol. Med. 2005, 34, 467–472. [Google Scholar] [CrossRef]
  47. Tovaru, S.; Parlatescu, I.; Gheorghe, C.; Tovaru, M.; Costache, M.; Sardella, A. Oral lichen planus: A retrospective study of 633 patients from Bucharest, Romania. Med. Oral Patol. Oral Cir. Bucal 2013, 18, e201–e206. [Google Scholar] [CrossRef]
  48. Eisen, D. The clinical features, malignant potential, and systemic associations of oral lichen planus: A study of 723 patients. J. Am. Acad. Dermatol. 2002, 46, 207–214. [Google Scholar] [CrossRef] [PubMed]
  49. Ingafou, M.; Leao, J.C.; Porter, S.R.; Scully, C. Oral lichen planus: A retrospective study of 690 British patients. Oral Dis. 2006, 12, 463–468. [Google Scholar] [CrossRef]
  50. Arduino, P.G.; Magliano, A.; Gambino, A.; Macciotta, A.; Carbone, M.; Conrotto, D.; Karimi, D.; Carrozzo, M.; Broccoletti, R. Risk of Malignant Transformation in 3173 Subjects with Histopathologically Confirmed Oral Lichen Planus: A 33-Year Cohort Study in Northern Italy. Cancers 2021, 13, 5740. [Google Scholar] [CrossRef]
  51. Lodi, G.; Giuliani, M.; Majorana, A.; Sardella, A.; Bez, C.; Demarosi, F.; Carrassi, A. Lichen planus and hepatitis C virus: A multicentre study of patients with oral lesions and a systematic review. Br. J. Dermatol. 2004, 151, 1172–1181. [Google Scholar] [CrossRef] [PubMed]
  52. Pitak-Arnnop, P.; Subbalekha, K.; Sirintawat, N.; Tangmanee, C.; Auychai, P.; Muangchan, C.; Sukphopetch, P.; Meningaud, J.P.; Neff, A. Are oral lichen planus patients at high risk of hepatitis C? A case-control study. J. Stomatol. Oral Maxillofac. Surg. 2022, 123, e37–e42. [Google Scholar] [CrossRef] [PubMed]
  53. Gorsky, M.; Epstein, J.B.; Hasson-Kanfi, H.; Kaufman, E. Smoking habits among patients diagnosed with oral lichen planus. Tob. Induc. Dis. 2004, 2, 103–108. [Google Scholar] [CrossRef] [PubMed]
  54. Kats, L.; Goldman, Y.; Kahn, A.; Goldman, V.; Gorsky, M. Oral lichen planus and thyroid gland diseases: Possible associations. BMC Oral Health 2019, 19, 169. [Google Scholar] [CrossRef]
  55. Arduino, P.G.; Karimi, D.; Tirone, F.; Sciannameo, V.; Ricceri, F.; Cabras, M.; Gambino, A.; Conrotto, D.; Salzano, S.; Carbone, M.; et al. Evidence of earlier thyroid dysfunction in newly diagnosed oral lichen planus patients: A hint for endocrinologists. Endocr. Connect. 2017, 6, 726–730. [Google Scholar] [CrossRef]
  56. López-Jornet, P.; Parra-Perez, F.; Pons-Fuster, A. Association of autoimmune diseases with oral lichen planus: A cross-sectional, clinical study. J. Eur. Acad. Dermatol. Venereol. 2014, 28, 895–899. [Google Scholar] [CrossRef]
  57. Pippi, R.; Romeo, U.; Santoro, M.; Del Vecchio, A.; Scully, C.; Petti, S. Psychological disorders and oral lichen planus: Matched case-control study and literature review. Oral Dis. 2016, 22, 226–234. [Google Scholar] [CrossRef]
  58. Burkhart, N.W.; Burker, E.J.; Burkes, E.J.; Wolfe, L. Assessing the characteristics of patients with oral lichen planus. J. Am. Dent. Assoc. 1996, 127, 648–656. [Google Scholar] [CrossRef]
  59. Vučićević Boras, V.; Savage, N.W.; Brailo, V.; Škrinjar, I.; Valter, K.; Alajbeg, I.; Dulčić, N.; Vidović Juras, D. The significance of oral and systemic factors in Australian and Croatian patients with oral lichen planus. Acta Dermatovenerol. Croat. 2014, 22, 97–102. [Google Scholar]
  60. Liu, S.; Tang, Y.; Li, J.; Zhao, W. Global, regional, and national trends in the burden of breast cancer among individuals aged 70 years and older from 1990 to 2021: An analysis based on the global burden of disease study 2021. Arch. Public Health 2024, 82, 170. [Google Scholar] [CrossRef]
  61. Bizuayehu, H.M.; Ahmed, K.Y.; Kibret, G.D.; Dadi, A.F.; Belachew, S.A.; Bagade, T.; Tegegne, T.K.; Venchiarutti, R.L.; Kibret, K.T.; Hailegebireal, A.H.; et al. Global Disparities of Cancer and Its Projected Burden in 2050. JAMA Netw. Open 2024, 7, e2443198. [Google Scholar] [CrossRef] [PubMed]
  62. Yiallourou, A.; Pantavou, K.; Markozannes, G.; Pilavas, A.; Georgiou, A.; Hadjikou, A.; Economou, M.; Christodoulou, N.; Letsos, K.; Khattab, E.; et al. Non-genetic factors and breast cancer: An umbrella review of meta-analyses. BMC Cancer 2024, 24, 903. [Google Scholar] [CrossRef]
  63. Arnold, M.; Morgan, E.; Rumgay, H.; Mafra, A.; Singh, D.; Laversanne, M.; Vignat, J.; Gralow, J.R.; Cardoso, F.; Siesling, S.; et al. Current and future burden of breast cancer: Global statistics for 2020 and 2040. Breast 2022, 66, 15–23. [Google Scholar] [CrossRef] [PubMed]
  64. Adamo, D.; Calabria, E.; Coppola, N.; Lo Muzio, L.; Giuliani, M.; Bizzoca, M.E.; Azzi, L.; Croveri, F.; Colella, G.; Boschetti, C.E.; et al. Psychological profile and unexpected pain in oral lichen planus: A case-control multicenter SIPMO studya. Oral Dis. 2021, 28, 398–414. [Google Scholar] [CrossRef] [PubMed]
  65. González-Moles, M.Á.; de Porras-Carrique, T.; Ramos-García, P. Association of oral lichen planus with hepatic disorders and hepatocellular carcinoma: Systematic review and meta-analysis. Med. Oral Patol. Oral Cir. Bucal 2023, 28, e229–e237. [Google Scholar] [CrossRef]
  66. Younossi, Z.M.; Wong, G.; Anstee, Q.M.; Henry, L. The Global Burden of Liver Disease. Clin. Gastroenterol. Hepatol. 2023, 21, 1978–1991. [Google Scholar] [CrossRef] [PubMed]
  67. Liu, Y.; Liu, L. Changes in the Epidemiology of Hepatocellular Carcinoma in Asia. Cancers 2022, 14, 4473. [Google Scholar] [CrossRef]
  68. Tan, E.Y.; Danpanichkul, P.; Yong, J.N.; Yu, Z.; Tan, D.J.H.; Lim, W.H.; Koh, B.; Lim, R.Y.Z.; Tham, E.K.J.; Mitra, K.; et al. Liver Cancer in 2021: Global Burden of Disease Study. J. Hepatol. 2024, 29, S0168-8278(24)02652-7. [Google Scholar] [CrossRef]
  69. Guarneri, F.; Giuffrida, R.; Di Bari, F.; Cannavò, S.P.; Benvenga, S. Thyroid Autoimmunity and Lichen. Front. Endocrinol. 2017, 8, 146. [Google Scholar] [CrossRef]
  70. De Porras-Carrique, T.; Ramos-García, P.; Aguilar-Diosdado, M.; Warnakulasuriya, S.; González-Moles, M.Á. Autoimmune disorders in oral lichen planus: A systematic review and meta-analysis. Oral Dis. 2023, 29, 1382–1394. [Google Scholar] [CrossRef]
  71. Díez, J.J.; Cabrera, L.; Iglesias, P.; Benavent, M.; López, G.; Argüello, G.; Parralejo, A.; López-Velázquez, A. Thyroid carcinoma in elderly people: Characterization using big data tools. Endocrinol. Diabetes Nutr. 2023, 70, 179–188. [Google Scholar] [CrossRef]
  72. Gonzalez Navarro, B.; Egido Moreno, S.; Omaña Cepeda, C.; Estrugo Devesa, A.; Jane Salas, E.; Lopez Lopez, J. Relationship between Oral Lichen Planus and Cardiovascular Disease of Atherosclerotic Origin: Systematic Review and Meta-Analysis. J. Clin. Med. 2024, 13, 4630. [Google Scholar] [CrossRef] [PubMed]
  73. Leroy, C.; Lesclous, P.; Dutot, N.; Anquetil, M.; Tessier, M.H. Erosive oral lichen planus: Think thymoma. Ann. Dermatol. Venereol. 2023, 150, 152–154. [Google Scholar] [CrossRef] [PubMed]
  74. Gubod, E.R.; Ramanathan, A.; Mohamad Zaini, Z.; Warnakulasuriya, S. Oral Lichen Planus in a Patient With a Thymoma: A Rare Finding. Cureus 2021, 13, e17376. [Google Scholar] [CrossRef]
  75. Le Gatt, P.; Nguyen, A.T.; Baaroun, V.; Rochefort, J. Oral Lichen Planus in Patients With Good’s Syndrome: A Literature Review. Cureus 2023, 15, e35177. [Google Scholar] [CrossRef] [PubMed]
  76. Vičić, M.; Hlača, N.; Kaštelan, M.; Brajac, I.; Sotošek, V.; Prpić Massari, L. Comprehensive Insight into Lichen Planus Immunopathogenesis. Int. J. Mol. Sci. 2023, 24, 3038. [Google Scholar] [CrossRef]
  77. Bernardini, N.; Skroza, N.; Tolino, E.; Mambrin, A.; Anzalone, A.; Balduzzi, V.; Colapietra, D.; Marchesiello, A.; Michelini, S.; Proietti, I.; et al. IL-17 and its role in inflammatory, autoimmune, and oncological skin diseases: State of art. Int. J. Dermatol. 2020, 59, 406–411. [Google Scholar] [CrossRef]
  78. He, D.; Li, H.; Yusuf, N.; Elmets, C.A.; Athar, M.; Katiyar, S.K.; Xu, H. IL-17 mediated inflammation promotes tumor growth and progression in the skin. PLoS ONE 2012, 7, e32126. [Google Scholar] [CrossRef]
  79. Shibabaw, T.; Teferi, B.; Ayelign, B. The role of Th-17 cells and IL-17 in the metastatic spread of breast cancer: As a means of prognosis and therapeutic target. Front. Immunol. 2023, 14, 1094823. [Google Scholar] [CrossRef]
  80. Song, X.; Wei, C.; Li, X. The potential role and status of IL-17 family cytokines in breast cancer. Int. Immunopharmacol. 2021, 95, 107544. [Google Scholar] [CrossRef]
  81. Banerjee, S.; Nahar, U.; Dahiya, D.; Gupta, R.; Mukherjee, S.; Sachdeva, N.; Sood, A.; Dey, P.; Radotra, B.; Bhansali, A. IL-17 A correlates with disease progression in papillary thyroid carcinoma. Diagn. Pathol. 2023, 18, 93. [Google Scholar] [CrossRef] [PubMed]
  82. Chen, X.; Zhang, S.; Wu, X.; Lei, Y.; Lei, B.; Zhao, Z. Inflammatory cytokines and oral lichen planus: A Mendelian randomization study. Front. Immunol. 2024, 15, 1332317. [Google Scholar] [CrossRef] [PubMed]
  83. Zhang, H.; Shen, G.; Yang, P.; Wu, M.; Li, J.; Li, Z.; Zhao, F.; Liang, H.; Da, M.; Wang, R.; et al. Causality between autoimmune diseases and breast cancer: A two-sample Mendelian randomization study in a European population. Discov. Oncol. 2024, 15, 396. [Google Scholar] [CrossRef] [PubMed]
  84. Ramos-García, P.; González-Moles, M.Á.; Warnakulasuriya, S. Oral cancer development in lichen planus and related conditions-3.0 evidence level: A systematic review of systematic reviews. Oral Dis. 2021, 27, 1919–1935. [Google Scholar] [CrossRef] [PubMed]
  85. Shengyuan, L.; Songpo, Y.; Wen, W.; Wenjing, T.; Haitao, Z.; Binyou, W. Hepatitis C virus and lichen planus: A reciprocal association determined by a meta-analysis. Arch. Dermatol. 2009, 145, 1040–1047. [Google Scholar] [CrossRef]
  86. Knol, M.J.; Le Cessie, S.; Algra, A.; Vandenbroucke, J.P.; Groenwold, R.H. Overestimation of risk ratios by odds ratios in trials and cohort studies: Alternatives to logistic regression. CMAJ 2012, 184, 895–899. [Google Scholar] [CrossRef]
  87. Soto, A.; Cvetkovic-Vega, A. Case-control studies. Rev. Fac. Med. Hum. 2020, 20, 138–143. [Google Scholar]
Jcm 13 07208 g001
Figure 1. Flow chart of the selections of patients included in the present study. Oral lichen planus (OLP).
Figure 1. Flow chart of the selections of patients included in the present study. Oral lichen planus (OLP).
Jcm 13 07208 g001
Table 1. Demographic characteristics of oral lichen planus (OLP) patients and control group; C: cigarette; U: units; *: statistically significant (p < 0.05). #: Pearson’s Chi2 test.
Table 1. Demographic characteristics of oral lichen planus (OLP) patients and control group; C: cigarette; U: units; *: statistically significant (p < 0.05). #: Pearson’s Chi2 test.
Variable OLP (%)Control (%)p Value #
GenderMale157 (26.2)157 (26.2)1
Female443 (73.8)443 (73.8)
AgeMean (SD)59.58 (±12.47)59.58 (±12.47)1
Tobacco useNo444 (74.0)375 (62.5)
Categories
≤10 c30 (5.0)67 (11.2)<0.001 *
>10 c36 (6.0)75 (12.5)<0.001 *
Cigar1 (0.2)2 (0.3)0.482
Former smoker89 (14.8)81 (13.5)0.658
Alcohol drinkerNo476 (79.3)445 (74.2)
Yes124 (20.7)155 (25.8)0.034 *
≤2 u47 (7.8)49 (8.2)0.611
>2 u53 (8.9)43 (7.2)0.511
Weekend24 (4.0)63 (10.4)<0.001 *
Atrophic-erosive formNo232 (38.7)
Yes368 (61.3)
Oral location2288 (48.0)
≥3312 (52.0)
History of cancerNo565 (94.2)584 (97.3)
Yes35 (5.8)16 (2.7)0.008 *
Table 2. Demographic characteristics of oral lichen planus (OLP) patients and control group; C: cigarette; U: units. #: Pearson’s Chi2 test; †: Test de Fisher.
Table 2. Demographic characteristics of oral lichen planus (OLP) patients and control group; C: cigarette; U: units. #: Pearson’s Chi2 test; †: Test de Fisher.
Variable OLP (%)Control (%)p Value
GenderMale6 (66.67)3 (33.33)1 †
Female29 (69.05)13 (30.95)
Age≤6012 (60.0)8 (40.0)0.286 #
>6023 (74.19)8 (25.81)
Tobacco useNo25 (75.76)8 (24.24)0.189 †
Categories
≤10 c1 (50.0)1 (50.0)
>10 c1 (25.0)3 (75.5)
Former smoker8 (66.67)4 (33.33)
Alcohol drinkerNo29 (70.73)12 (29.27)0.912 †
≤2 u2 (66.67)1 (33.33)
>2 u2 (50.0)2 (50.0)
Weekend2 (66.67)1 (33.33)
Table 3. Type of cancers in patients with OLP and the control group with history of cancer. 1. Patient with two types of cancer location. In square brackets, ranges of age. In parentheses, percentages.
Table 3. Type of cancers in patients with OLP and the control group with history of cancer. 1. Patient with two types of cancer location. In square brackets, ranges of age. In parentheses, percentages.
Type of TumorOLP
F/M		CG
F/M		OLP
Mean Age
[Range]		CG
Mean Age
[Range]
Breast11/03/066.4 [57–77]65.3 [55–75]
Skin
Melanoma1/01/07238
Basal carcinoma3/01 1/261.6 [43–81]59.6 [43–70]
Colon1/21/054.3 [35–66]61
Small intestine0/1 67
Thyroid2/0 52 [50–54]
Cervix7 1/02/065.1 [53–71]70.5 [66–75]
Ovary2/0 73.5 [71–76]
Lymphatic1/02/05862 [57–67]
Thymus1/0 46
Stomach0/12/06256.5 [55–58]
Vocal cord0/1 67
Hepatocellular carcinoma1/0 63
Peritoneum1 1/0 62
Bladder 0/1 65
Rectum 1 1/0 66
Nail 1/0 61
Total30 (85.71)/13 (81.25)/
5 (14.29)2 (18.75)
Table 4. Results of the univariate and multivariate analyses. OR: Odds ratio; CI: confidence interval (95%); SD: standard derivation; *: statistically significant (p < 0.05).
Table 4. Results of the univariate and multivariate analyses. OR: Odds ratio; CI: confidence interval (95%); SD: standard derivation; *: statistically significant (p < 0.05).
VariableOLP
n (%)		Control Group n (%)OR Univariate (CI, p Value)OR Multivariate (CI, p Value)
Sex
   Female (%)443 (50.0)443 (50.0)--
   Male (%)157 (50.0)157 (50.0)1.00 (0.77–1.29, p = 1.000)1.10 (0.84–1.44, p = 0.478)
Age
   ≤60292 (50.0)292 (50.0)--
   >60308 (50.0)308 (50.0)1.00 (0.80–1.25, p = 1.000)1.00 (0.77–1.29, p= 0.884)
Tobacco use
   No (%)444 (54.2)375 (45.8)--
   ≤10 c (%)30 (36.9)67 (69.1)0.38 (0.24–0.59, p < 0.001 *)0.42 (0.26–0.67, p < 0.001 *)
   >10 c (%)36 (32.4)75 (67.6)0.41 (0.26–0.61, p < 0.001 *)0.41 (0.26–0.63, p < 0.001 *)
   Cigar (%)1 (33)2 (66.7)0.42 (0.02–4.42, p = 0.482)0.91 (0.64–1.29, p = 0.592)
   Former smoker (%)89 (52.4)81 (47.6)0.93 (0.67–1.29, p = 0.658)0.39 (0.02–4.07, p = 0.439)
Alcohol drinker
   No (%)476 (51.7)445 (48.3)--
   ≤2 u (%)47 (49.0)49 (51.0)0.90 (0.59–1.37, p = 0.611)1.04 (0.67–1.62, p = 0.844)
   >2 u (%)53 (55.2)43 (44.8)1.15 (0.76–1.76, p = 0.511)1.36 (0.87–2.13, p = 0.179)
   Weekend (%)24 (27.6)63 (72.4)0.36 (0.21–0.57, p < 0.001 *)0.44 (0.26–0.73, p = 0.002 *)
History of Cancer
   No (%)565 (49.2)584 (50.8)--
   Yes (%)35 (68.6)16 (31.4)2.26 (1.26–4.24, p = 0.008 *)2.21 (1.21–4.19, p = 0.012 *)
Table 5. Logistic regression models to analyze differences for “history of cancer or not” and the following variables: alcohol drinker, tobacco use, age, sex. AIC: Akaike information criteria; df: degrees of freedom.
Table 5. Logistic regression models to analyze differences for “history of cancer or not” and the following variables: alcohol drinker, tobacco use, age, sex. AIC: Akaike information criteria; df: degrees of freedom.
ModelDfDevianceAIC
<none> 1607.81625.8
History of cancer 11614.61630.6
Alcohol drinker31621.71633.7
Tobacco use41635.91645.9
Age11607.81625.8
<none> 1607.71627.7
History of cancer (yes/no)11614.61632.6
Alcohol drinker31621.51635.5
Tobacco use41635.91647.9
Sex11607.71627.7
Age116.7.71627.7
<none>
History of cancer (yes/no)11614.51634.5
Alcohol drinker31621.21637.2
Tobacco use41635.91649.9
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

García-Pola, M.; Rodríguez-Fonseca, L.; Llorente-Álvarez, C.; Llorente-Pendás, S. History of Breast Cancer in Patients with Oral Lichen Planus: A Case–Control Study. J. Clin. Med. 2024, 13, 7208. https://doi.org/10.3390/jcm13237208

AMA Style

García-Pola M, Rodríguez-Fonseca L, Llorente-Álvarez C, Llorente-Pendás S. History of Breast Cancer in Patients with Oral Lichen Planus: A Case–Control Study. Journal of Clinical Medicine. 2024; 13(23):7208. https://doi.org/10.3390/jcm13237208

Chicago/Turabian Style

García-Pola, María, Lucía Rodríguez-Fonseca, Claudia Llorente-Álvarez, and Santiago Llorente-Pendás. 2024. "History of Breast Cancer in Patients with Oral Lichen Planus: A Case–Control Study" Journal of Clinical Medicine 13, no. 23: 7208. https://doi.org/10.3390/jcm13237208

APA Style

García-Pola, M., Rodríguez-Fonseca, L., Llorente-Álvarez, C., & Llorente-Pendás, S. (2024). History of Breast Cancer in Patients with Oral Lichen Planus: A Case–Control Study. Journal of Clinical Medicine, 13(23), 7208. https://doi.org/10.3390/jcm13237208

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop