CLINICIAN'S CORNER

Tongue squamous cell carcinoma in youngnonsmoking and nondrinking patients: 3 clinicalcases of orthodontic interest

Alan Roger Santos-Silva,a Marco Aurelio Carvalho Andrade,b Jacks Jorge,c Oslei Paes Almeida,d

Pablo Agustin Vargas,e and Marcio Ajudarte Lopesf

Piracicaba, S~ao Paulo, Brazil

FromPiraciaAssisbPhDcAssodTituleAssofTitulAll auPotenAddrePO BoalanroSubm0889-Copyrhttp:/

Oral squamous cell carcinoma traditionally affects older men who smoke and drink. A change in this profile hasbeen reported because of an increased incidence in young nonsmoking and nondrinking patients. The purposeof this article was to describe a series of young nonsmoking and nondrinking patients diagnosed with tonguesquamous cell carcinomawho had recently received orthodontic treatment or evaluation. Details regarding diag-nosis, treatment, follow-up, and disease evolution are presented, with a review of the pertinent literature. Ortho-dontists often treat young adults, who have frequent dental appointments and long-term follow-ups. Thus,practitioners should pay special attention to young patients during dental consultations, since the incidence ofmalignant oral lesions in this segment of the population seems to be increasing. (Am J Orthod DentofacialOrthop 2014;145:103-7)

Squamous cell carcinoma (SCC) accounts for morethan 90% of all oral malignancies; it is most com-mon in men in their sixth and seventh decades of

life who have used tobacco and alcohol for longperiods.1-3

In the overall population, themost common anatomicsite for oral SCC is the lower lip, and the intraoral site withthe highest incidence is the lateral border of the tongue,followed by the floor of the mouth, the soft palate, theretromolar area, and the gingiva.3 Early recognition oforal SCC appears to confer a survival advantage and isalso associated with less morbidity and requires lessmutilating surgery. In this context, several potentiallymalignant lesions can progress to oral SCC. The 3 mostoften seen potentially malignant oral lesions are actinic

the Department of Oral Diagnosis, Semiology and Pathology Areas,caba Dental School, University of Campinas, Piracicaba, S~ao Paulo, Brazil.tant professor in oral medicine.student.ciate professor in oral pathology.ar professor in oral pathology.ciate professor in oral pathology.ar professor in oral pathology.thors have completed and submitted the ICMJE Form for Disclosure oftial Conflicts of Interest, and none were reported.ss correspondence to: Alan Roger Santos-Silva, Piracicaba Dental School,x 52, University of Campinas, 13414-903, Piracicaba, SP, Brazil; e-mail,ger@fop.unicamp.br.itted, October 2011; revised and accepted, September 2012.5406/$36.00ight � 2014 by the American Association of Orthodontists./dx.doi.org/10.1016/j.ajodo.2012.09.026

cheilitis, a reddish swelling induced by chronic exposureto sunlight that precedes lower-lip SCC; erythroplakia(red patch), the type of lesion most likely to progress tocarcinoma; and leukoplakia (white patch), which canpresent clinically as nodular leukoplakia, speckled leuko-plakia (erythroleukoplakia), or proliferative verrucousleukoplakia. Oral SCC may also present clinically as leu-koplakia or erythroplakia but is mainly seen as induratedulcers or lumps, granular ulcers with tissue infiltrationand raised exophytic margins, or a nonhealing extractionsocket.3 Thus, clinicians should be aware when any ofthese features persist for more than 2 weeks because itmight be a sign of oral malignancy.

Recently, evidence based on research in several coun-tries has shown an important increase in the incidence ofthese tumors among young patients.2,4-8 Despite thisevidence, oral SCC and potentially malignant disordersare still considered uncommon in young patients,although one cannot deny the difficulties involved forgeneral practitioners to be able to correctly interpretthese lesions, which could result in underestimation oftheir prevalence during dental care.4,9-11 Thus, oralSCC is generally only diagnosed in more advancedstages and then requires more aggressive treatment,and the prognosis is also worse. However, there arestill controversies regarding the prognosis of oral SCCin younger people. Some studies report a favorableclinical prognosis,4,7,12 whereas others show a worseprognosis for young people.5,13 Only a few studies

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Fig 1. Oral examination of patient 1 demonstrating excel-

104 Santos-Silva et al

have so far focused on gaining a better understanding oforal cancer in young patients.14-17 Therefore, the aim ofthis article was to describe 3 clinical cases of oral SCCdiagnosed in nonsmoking and nondrinking patientsunder 40 years of age who attended an oral medicinecenter within a short time frame. Interestingly, all thepatients had recent orthodontic treatment orevaluation. In addition, a literature review wasundertaken to provide more information about theemerging issue of oral SCC in young patients.

lent occlusion during the final stage of orthodontic treat-ment. This photo was obtained at the moment ofdiagnosis of tongue SCC.

Fig 2. Erythroleukoplakic lesion on the left lateral borderof the tongue of patient 1.

Fig 3. Histopathologic aspects of the SCC diagnosed inpatient 1. Note the nests and cords of atypical hyperchro-matic and pleomorphic epithelial cells invading deep con-nective tissues and muscle fibers.

CASE REPORTS

Patient 1 was a 21-year-old white woman, anonsmoker and nondrinker in the final stage of ortho-dontic treatment (Fig 1), who came to our clinic at Pira-cicaba Dental School, Piracicaba, S~ao Paulo, Brazil,complaining about a white spot on her tongue. Shereported a mildly uncomfortable sensation associatedwith the lesion, which had evolved over 6 months. Shementioned that she had asked the orthodontic staff aboutthe lesion andwas told that it was not a significant lesion.The intraoral examination showed an erythroleukoplakiaon the left lateral border of the tongue, measuringapproximately 2.03 2.0 cm (Fig 2). An incisional biopsywas performed, and histopathologic analysis showednests and cords of atypical hyperchromatic and pleomor-phic epithelial cells invading deep connective tissue.Atypical mitoses were found in several areas of theanalyzed tissue (Fig 3). Thus, the diagnosis of SCC wasconfirmed, and the patient was referred formedical treat-ment. Additional examinations did not identify anyregional or distant metastases, and the clinical stagingof the patient at diagnosis was a T1N0M0 classification.(T describes the size of the primary tumor, N describesregional lymph nodes that are involved, and M describesdistant metastasis.) Treatment consisted of a left partialglossectomy associatedwith homolateral supraomohyoidneck dissection. A reconstruction was immediately per-formed with microsurgery grafting using a mucocuta-neous flap from her left biceps. The patient is still underfollow-up and has shown no recurrence or metastasis af-ter 48 months.

Patient 2 was a 34-year-old white man, a nonsmokerand nondrinker, who was referred from a physician toour clinic. He had completed orthodontic treatmentwith fixed appliances 4 years earlier, but he was not un-der postorthodontic follow-up. The intraoral examina-tion showed an infiltrative ulcer on the right lateralborder of the tongue, and the main diagnostic hypothe-sis was SCC. The lesion was approximately 4.03 3.0 cmin size and was painful on palpation (Fig 4). The diag-nosis of oral SCC was confirmed through incisional

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biopsy and histopathologic analysis. The patient wasreferred to medical staff, who staged his tumor asT2N0M0. However, he refused the therapeutic proposalof a partial glossectomy with supraomohyoid neckdissection. The patient, of his own accord, went to

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Fig 4. Infiltrative ulcer on the right lateral border of thetongue of patient 2.

Fig 5. Occlusion of patient 3 observed at the moment ofdiagnosis of tongue SCC.

Fig 6. Large ulcer on the left lateral border of the tongueinfiltrating the floor of the mouth of patient 3.

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another physician, who performed a “conservative sur-gery” with an intraoral approach and without cervicaldissection. The histopathologic examination of the sur-gical sample detected compromised surgical margins,which led the patient to postoperative radiotherapy.However, he also refused adjuvant radiotherapy. The pa-tient died 10 months after the diagnosis from localpersistence of the disease and cervical metastasis.

Patient 3 was a 29-year-old white woman, anonsmoker and nondrinker, who came to our clinic com-plaining of “a wound on the tongue” that she hadobserved after an initial orthodontic evaluation, approx-imately 40 days before coming to our clinic (Fig 5). Thelesion was associated with a mildly uncomfortablesensation. The intraoral examination identified a 5.0 34.0-cm ulcer on the left lateral border of the tongue,with infiltration to the floor of the mouth and impreciselimits (Fig 6). An incisional biopsy was performed, andhistopathologic analysis detected an intense prolifera-tion of atypical epithelial tissue, atypical dyskeratosis,and mitoses associated with necrotic areas, confirmingthe clinical impression of SCC. She was referred for treat-ment with medical staff, who staged her tumor asT3N2M0 and performed a left hemiglossectomy associ-ated with bilateral supraomohyoid dissection and post-operative radiotherapy (total dose of 6.100 cGy). Thepatient had pulmonary metastasis 12 months after treat-ment and cervical metastasis 16 months after diagnosis.She is currently being treated by palliative chemotherapyin an attempt to control the disease.

DISCUSSION

There are several variations in the literature regardingthe criteria for defining a young patient with oral SCC.Apparently,most of the published studies have establishedthe age limit as 40 years.1,4 However, many studieshave considered age 45 years as the limit.2,5,7,14,18,19

Interestingly, the analyses that considered patients

American Journal of Orthodontics and Dentofacial Orthoped

under the age of 45 years found risk factors, sexprevalence, and clinical stages similar to those describedfor oral SCC in elderly patients.14,19 This findingsuggests that the ideal age for considering a patient asyoung for oral SCC is 40 years.

From 1960 to 1990, the incidence of tongue SCC inyoung Scandinavian adults, ages 20 to 39 years, increasedby 5-fold among men and 6-fold among women, dimin-ishing the ratio between the sexes, whereas for elderly pa-tients the values doubled inboth sexes.4 Similarly, patientsup to 35 years of age, from different French medical cen-ters, showed a male-to-female ratio of 1.88:1; the normalratio for elderly patients in France is 10:1. More recently,Patel et al,8 when studying trends in oral SCC from 1975to 2007 in the United States, showed that the prevalenceof tongue SCC is increasing among young white people18 to 44 years of age, particularly among women. Thus,according to these authors, young white women mightbe a new, emerging head and neck cancer-patient popu-lation. Interestingly, themean age at diagnosis of our caseseries was 28 years (range, 21-34 years); although small,our sample clearly shows some characteristics describedabove for the clinical profiling of young patients withoral SCC.

Apparently, there are no individualized treatmentprotocols for young patients with oral SCC; thus, the

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therapeutic approaches follow the models used forelderly patients (surgery, radiotherapy, and, occasion-ally, chemotherapy) and are based on the samecriteria.13,16,20,21 Remarkably, recent results havesuggested that the lack of a specific treatmentprotocol could be associated with a negative impact onthe prognosis and survival of young patients with oralSCC.13 The same authors suggested that physicianscould be influenced by these patients' young age duringsurgical planning; this would cause incomplete tumorresections in an attempt to preserve functioning. As anadditional challenge, the small numbers of oral SCC inthe young population limits medical experience.13

It is suggested that several factors could be related, toa greater or lesser degree, to the clinical behavior of oralSCC in young patients. Among them are a possibleenhanced genetic susceptibility to tumors, increasedgenomic instability, human papillomavirus (HPV) infec-tion, and inadequate therapeutic approaches (conserva-tive surgical procedures).2,4,7,13,17

HPV infection with high-risk types 16 and 18 hasbeen widely reported as a prominent mechanism behindthe development of SCC of the oropharynx. However, therole of HPV in the development of oral SCC is still a mat-ter of debate, especially in young patients.22

It is difficult to determine whether young adults withoral SCC represent a spectrum or are a distinct group ofhead and neck cancer patients. Apparently, it seemsmore likely that they are both, falling into 3 majorgroups: (1) those in the 40- to 45-year age group whoreport a high level of risk-factor exposure (tobacco andalcohol) might simply be a continuation of the spectrumseen in older patients; (2) men with oropharyngeal can-cer, including many nonsmokers, some of whom are 45years old, but most are somewhat older, who are anemerging group related to a high risk for HPV infection;and (3) a third distinct group of 40-year-old patients,usually female nonsmokers, with oral cancer.22 It hasbeen suggested that HPV must be a factor in the lattergroup, but some studies indicate otherwise.22-24 So far,the principal findings in molecular studies of youngpatients with oral SCC are that the tumors developingin these patients are markedly different at a geneticlevel, with some studies reporting that high risk forHPV infection might play an important role in carcino-genesis in this group.22

Reports suggest that tumors with HPV positivityshow improved survival rates, although consensus hasyet to be achieved. Further studies to establish the realrisk of HPV in the development and clinical behaviorof oral SCC in young patients are needed.25

Most importantly, the moment of diagnosis is of ma-jor importance for a good prognosis, but oral SCC in

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young patients seems to be frequently diagnosed in itsadvanced stages, which greatly compromise treatment,quality of life, and survival rates.14

The histories of the patients described here illustrateour points in this discussion. Patient 1 was undergoinglong-term orthodontic treatment when, independently,her lesion was identified. As an aggravating circum-stance, even though she considered it an uncommonoral alteration, the lesion was underestimated by her or-thodontic staff. Furthermore, she was not referred for aspecialized evaluation. This finding exposes theapparent limitations of many dental clinicians who, dur-ing their consultations, do not perform systematic oralexaminations on their patients. This evidently impairsthe identification of oral lesions, especially lesionslocated on less-visible anatomic regions, such as thelateral border of the tongue. Nevertheless, the fact thatthe patient persisted in looking for help and was thusdiagnosed at an early stage of the disease probably ex-plains her favorable outcome. Unfortunately, this wasnot the case with patient 3, who was diagnosed at anadvanced stage of the disease. Patient 2, despite hisfavorable stage of disease at the diagnosis (T2N0M0),died because of the persistence of the disease, whichwas incompletely treated. This clinical situation suggeststhat psychosocial factors can motivate young patients torefuse the treatment, negatively influencing the clinicalevolution of the disease and, as a consequence, theprognosis.

Analysis of the cases presented in this article, in lightof the relevant literature, suggests that oral SCC inyoung patients is an important issue in contemporarydental practice and that it might represent a distinctclinical entity because of its apparent increase innonsmoking and nondrinking women.2,4,5,8,13,17 Mostimportantly, systematic oral examinations are a simple,inexpensive, and potentially important tool forpromoting oral and general health.

Recent case reports have strengthened the importanceof systematic oral examinations in patients undergoingorthodontic treatment, especially because orthodontistsare considered to be well-placed dental specialists torecognize oral lesions at their initial stages of develop-ment, since their treatments require frequent dental ap-pointments and long-term follow-ups.11,26-29

CONCLUSIONS

The establishment of full oral examinations, includingthe entire oral mucosa, as routine in orthodontia couldsignificantly contribute to the early diagnosis of oral can-cer.11,29 Overall, more attention should be paid to youngpatients during dental consultations, since the incidence

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Santos-Silva et al 107

of malignant oral lesions in this segment of thepopulation seems to be increasing.

ACKNOWLEDGMENTS

We thank Renato Nicol�as Hopp for his professionalassistance during the patients' dental appointments.

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