Oral Potentially Malignant Disorders and Cancerdental.anamai.moph.go.th/elderly/2558/Project13-14aug15_03.pdf · Oral Potentially Malignant Disorders and Cancer Anak Iamaroon Professor

Oral Potentially Malignant Disorders and Cancer

Anak IamaroonProfessor of Oral Pathology

Faculty of Dentistry,

Chiang Mai University

Chiang Mai

MahajanakaRight perseverance

Penetrating wisdom

Health

Oral Cancer at a Glance

!Head and neck cancer accounts

for 10% of all human cancers

!40% of them occur in the mouth

!Oral cancer is the fifth most

common cancer in men

Oral Cancer at a Glance

!>90% of oral cancer are squamous

cell carcinoma

!75% of cases are diagnosed

between the ages of 50-70 years

!High mortality

High Mortality

IARC, 2011

Risk Factors: Tobacco use

!Main etiological factor

! >30 carcinogens: aromatic hydrocarbons

and nitrosamines

! 90% of patients use tobacco

! Smokers are 6-16 times more likely to

develop oral cancer

www.aksorn.com

Chewing Tobacco

www.cramersportsmed.com

Alcohol Consumption

! Second most important factor

! 75% of patients drink alcohol

! Drinkers have 6 times higher risk

!Combination of tobacco use and alcohol

drinking enhances the risk by 100-fold

Betel Quid Chewing Habit

! Betel nut usage increases oral cancer risk

28-fold

! TAIPEI, Taiwan -- 89 times if coupled with

smoking, and a staggering 123 times for

the person who smokes and drinks

"Betel nut beauty" on the road between Taipei and Hsinchu.

!Oral cancer rates up 280%; betel nut key

driver: study

! TAIPEI -- Taiwan's rate of oral cancer —

one of the island's top 10 causes of death

— has nearly quadrupled in the past 40

years

Other Risks

! UV radiation: Caucasians

Lip: tongue: lung = 1:2.5:33

(Chiang Mai Cancer Registry, 1996)

! Immunosuppression

! Low intake of fresh fruit and vegetable

! Low socio-economic status

! Poor oral hygiene

Emerging Risk:

Human Papillomavirus (HPV)

www.knowcancer.net/wp-content/uploads/2007/08

HPV and Oral CancerGillison et al (2007)

! They examined nearly 46,000 cases of

oral cancer occurring between 1973 and 2004

! They split the cases into 2 groups: those

linked to HPV (over 17,500) and those that were not (over 28,000).

HPV and Oral Cancer

!diagnosed at younger ages than HPV-unrelated ones (mean

ages at diagnosis were 61.0 and 63.8 years respectively)

! Incidence of HPV-related oral cancers rose significantly from 1973

to 2004, particularly among white,

younger men

Malmo Study

!Comparing 132 patients with mouth cancer with a control group of 320 healthy people,

36% of the cancer patients were carriers of HPV

while only 1% of the control group had the virus.

! HPV-related head and neck cancers

differ substantially from HPV-unrelated ones

!Genetic, molecular, epidemiological and

clinical levels

! HPV-related cancers respond better to

treatment and

! have better survival

Ndiaye et al., Lancet Oncology, 2014

Oral cavity: 72 studies, 5478 cases, HPV 24.2%

Prevalence of HPV-related cancer by anatomical site

Prevalence of HPV-related cancer by geographical region

!HPV-related oral cancer

becomes a global burden

particularly in Asian populations

!Significant of HPV infection in

oral cancer in Thai population is under investigation

Take Home Message Clinical Features

!Exophytic/verrucous mass

!Ulcer

!Leukoplakia

!Erythroplakia

Lip Cancer

Floor of the Mouth

Attachment between tongue and floor of the mouth

Tongue Cancer,Examine all surfaces esp. lateral borders.

Clinical features:

erythroplakia

andexophytic mass

20 year-old Thai man with 4 cm painful ulcer on lateral

tongue, ipsilateral cervical lymph nodes involvement,Distant metastasis undetected.

Gingival and Buccal

Cancer,Association with betal quidchewing habit?

Squamous Cell Carcinoma

Squamous Cell Carcinoma

Tooth mobility

anddisplacement

Verrucous Carcinoma

!A variant of SCC.

!Good prognosis

!No invasion

Verrucous Carcinoma

Diagnosis

!Biopsy

(histopathology)

Well-differentiated Moderately Differentiated

Poorly Differentiated

VerrucousCarcinoma

Courtesy of Dr. Surawut Pongsiriwet

Erythro-leukoplakia

56-yr-old male: heavy smoker & alcohol drinker Microinvasive Squamous Cell Carcinoma

Distributions by year of all patients and young people with

oral SCC from 1991-2000. The X axis represents years and the Y axis

represents percentages.(Iamaroon et al., Int J Oral Maxillofac Surg, 2004)

Patients under 45 years

of age

12.8%

Males: females 1.3:1

Iamaroon et!al.,!

2004

Iamaroon et!al.,!

2004Iamaroon et!al.,!2004

Current Situation of

Oral Cancer

in Upper Northern Thailand: 10 year

Analysis

2001-2010

(Journal of Oral Science, 2015, revised)

Objective

To identify

• Rate of occurrence

• Demographic

distribution

• Stage

• Site

• Histologic differentiation

• Risk factor

• Survival rate

OBJECTIVES

Methods

!Hospital-based study: MaharajNakorn Chiang Mai University Hospital

!Cancer registry 2001-2010

!Squamous cell carcinoma of the oral cavity

!Tonsil, salivary glands and oropharynx were excluded

Increased the number of patients

2001-2010

874 cases

1991-2000

587 CASES

Age distribution in

all patients

64.0

MEDIAN

15-97 years old

RATE OF OCCURRENCE

874 CASES

Percentage of patients under 40 years of age

WORLDWIDE

4-6% (LLEWELLYN ET AL., 2001)

1-6% (OLIVER ET AL., 2000)

4.1%

Age Distribution

in Patients under 40

33.5

MEDIAN

Compared with previous study

!About 50% of all cancer

patients chewed betel quid

!About 25% of younger patients

chewed betel quid

!Indicating betel quid chewing

is vanishing habit in Thailand

Survival curve of all patients

Five-year

survival rate

24.4%

SURVIVAL CURVE COMPARISON BETWEEN TWO AGE GROUPS

under 40

Five-year

survival rate

47.2%

over 40

Five-year

survival rate

23.4%

p=0.002

SURVIVAL CURVE COMPARISON BETWEEN MALES AND FEMALES

Female

Five-year

survival rate

29.1%

Male

Five-year

survival rate

21.2%

p=0.017

SURVIVAL CURVE AMONG STAGES

Stage I

Five-year

survival rate

50.8%

Stage IV

Five-year

survival rate

15.7%

Conclusions

!Cancer of the mouth esp. tongue

remains a constant and serious

problem in northern Thailand

!Most patients came in late stages

suggesting systematic screening

program for PMDs and early lesions

!Treatment modalities need to be improved

Potentially Malignant DisordersPMDs

Why do we have to look for PMD?

! Reduce a chance of malignant

transformation

!Minimize risk factors in patients

! Reduce burden of oral cancer in both patients and society

PMDs

!Leukoplakia

!Erythroplakia

!Lichen planus

!Oral submucous fibrosis

!Actinic cheilitis

Oral Leukoplakia (OL)

!Predominantly white plaques of

questionable risk, having excluded

(other) known diseases or disorders

that carry no increased risk of

cancer.

(Warnakulasuriya et al, 2007; Arduino et

al., 2013)

What are non-leukoplakiawhite lesions?

1. Lichen planus

2. Lupus erythematosus

3. Frictional keratosis

4. Chronic cheek chewing

5. Nicotine stomatitis

6. Leukoedema

7. White sponge nevus

8. Candidiasis: pseudomembranous

9. Burns: chemical or thermal

Frictional keratosis

Courtesy of Assoc. Prof. Dr. Surawut Pongsiriwet

Chronic Cheek Chewing


Chronic Lip Chewing


Nicotine Stomatitis


Leukoedema


White Sponge Nevus

Iamaroon A and Pongsiriwet S. Oral white sponge naevus: case report. Dent Update, 2003.

Iamaroon A and Pongsiriwet S.

Oral white sponge naevus: case report. Dent Update, 2003.

Pseudomembranous Candidiasis


Pseudomembranous Candidiasia and Hairy Leukoplakia

Thermal Burn


Prevalence

! 2% of population worldwide (Petti, 2003)

!Overestimated?

! 1% Annual malignant transformation rate,

! Development of oral cancer in 20 per

100,000

populations per year.

! < 0.5 %

(van der Waal, 2008)

Studies in Thailand

! Jainkittivong et al., 2002: a survey on 500

elderly in oral med clinic, CU

! 4.8% OL

! Associated with tobacco use especially in males

In Thailand

! Lapthanasupkul et al. (2007):

! 123 cases (1.7%) of OL in 7,177 biopsy

specimens.

! The most common site: buccal mucosa

(28.5%), followed by alveolar mucosa

(18.7%) and tongue (16.3%).

!Male:female = 1.2:1

!Microscopic study: ! Hyperkeratosis (60.9%)

! Epithelial dysplasia (10.6%),

! Squamous cell carcinoma (4.9%)

Risk factors

! Tobacco use/betel quid chewing

! Patients with OL often are

smokers/betel quid chewers

! Reduction/disappearance of

OL occur when patients cease

tobacco/betel quid use.

Alcohol

!Controversial

! Independent risk factor regardless of beverage type or drinking pattern.

hpv

A public awareness since Michael Douglas announced he had “oral cancer” due to HPV infection

Candidal infection

!Candidal leukoplakia/chronic

hyperplastic candidiasis

Candidal Leukoplakia/Chronic Hyperplastic Candidiasis

Prevalence of HPV

! Normal oral mucosa: 10%

! Nondysplastic OL: 20.2%

! Dysplastic/CIS OL: 26.2%

!OSCC: 46.5%

(Miller & Johnstone, 2001)

Study in Thailand

! Khovidhukit et al., 2008

! 17 cases of OL

! 16 cases of LP

! 32 cases of OSCC

! A case of OSCC was positive for HPV by PCR

Clinical features

! Homogeneous OL: flat, thin, uniform white

color

! Nonhomogeneous OL: white or white-

and-red lesion (“erythroleukoplakia”), that

may be either irregularly flat (speckled) or nodular or verrucous

Homogeneous leukoplakia




Non-homogeneous leukoplakia

Nonhomogeneous leukoplakia


Nonhomogeneous leukoplakia


Nonhomogeneousleukoplakia56-yr-old male: heavy smoker & alcohol

drinker

Microinvasive Squamous Cell Carcinoma

Proliferative Verrucous Leukoplakia (PVL)

Multifocal verrucous leukoplakias,

Resistance to treatment

High rate of malignant transformation

More prevalent among elderly women. With/without a history of tobacco use.

Silverman and Gorsky (1997): Study on 54 PVLs

70.3% malignant transformation

PVL with Verrucous CarcinomaElderly Female

Courtesy of Assoc. Prof. Dr. Surawut Pongsirwet

What percentage of OL transform into cancer?

! Ranging widely from 0.13% to 36.4%

! 1.36%: a systematic review on world

prevalence of OL (Petti and Scully, 2003)

! 15-20% of nonhomogeneous leukoplakia

! 3% of homogeneous leukoplakia

(Holmstrub et al., 2006)

Risk factors of malignant transformation

1. Female gender

2. Long duration of leukoplakia

3. Leukoplakia in non-smokers

4. Location on tongue, floor of the mouth and soft palate

5. Size > 200 mm2 (OR=5.4)

6. Nonhomogeneous leukoplakia (OR=7.0)

7. Presence of dysplasia8. DNA ploidy status

9. Presence of C. albicans(Lee et al, 2000; Holmstrub et al., 2006; van der Waal, 2009)

Dysplasia

! Histologic changes of the epithelial cells

!Mild

!Moderate

! Severe

!Carcinoma in situ

Hyperkeratosis

Mild Dysplasia

Severe Dysplasia

Carcinoma in situ

Nonhomogeneous OL with 11 years follow-up

! 58-yr-old female with unknown risks

! 11 years ago: leukoplakia with mild

dysplasia

! 5 years later: leukoplakia with moderate

dysplasia

! In 2009: wide surgical excision

Recurrence: October 2013

Courtesy of Dr. Darusakorn Maneeratana

risk factors of malignant transformation

1. Female gender

2. Long duration of leukoplakia

3. Leukoplakia in non-smokers

4. Location on tongue, floor of the mouth and soft palate

5. Size > 200 mm2 (OR=5.4)

6. Nonhomogeneous leukoplakia (OR=7.0)

7. Presence of dysplasia8. DNA ploidy status

9. Presence of C. albicans

(Lee et al, 2000; Holmstrub et al., 2006; van der Waal, 2009)

Severe dysplasia/carcinoma in situ

Severe dysplasia/Carcinoma in situ

Treatment plan

! Laser surgery

! Long-term follow-up

Erythroplakia

! A fiery red patch that cannot be

characterized clinically or pathologically as any other definable disease

Prevalence

! 0.02% - 0.2%

Villa et al., 2011

Risk factors

! Smoking

! Alcohol

! HPV

Clinical presentation

! The middle-aged or elderly

! No gender preference

Lateral Tongue

Courtesy of Assoc. Prof. Dr. Surawut PongsirwetCourtesy of Assoc. Prof. Dr. Surawut Pongsirwet

Differential Diagnosis

! Erythematous candidiasis

! Nonspecific mucositis

! Vascular lesions

Erythematous Candidiasis

histology

! Significant dysplasia

!Carcinoma in situ

! Invasive carcinoma

Malignant transformation

! Unclear rate in population

! 45% in hospital based studies

What have we learnt?

!Many studies shown surgical approach

did not prevent all premalignant lesions

from malignant development.

! 12% of surgically treated cases developed

cancers

!Without surgical intervention, 4% of cases

developed cancers (Holmstrub et al., 2006).

!New treatment modalities?

What are lying in the future?

!Chemoprevention of Head and

Neck Cancer with Celecoxib and

Erlotinib: Results of a Phase Ib and

Pharmacokinetic Study (Saba et al.,

2013)

! Erlotinib: EGFR inhibitor

!Celecoxib: Cox2 inhibitor

Oral Lichen Planus (OLP)

! !" #$%&'$()*+,-.*/012345#67859:;-1&2<,=(#(middle-aged) 9$>%5#678)7=%,&?!345#6789:@=(@A !" #$8%&<B 65 +%=678!; -&.1 C=90A!DE,F9#;=.*/34GA84;%&.*/)?A(>% &>/% 0>%2F280

$%=<=0,(>%<@ C#!DE,F9#;=%>/#.*/%,H34GA8(>% 9=>%2 $@0I* !,2 F<B

3A,#!,2!$%&'$(0120*2$BH,&D1-5#<12JKB)00,D$

Clinical features

!Andreasen (1968) GA8HE,F#2 OLP !" # 6 L#@A!$; ,=F9 (reticular)

!D?;0D1# (papular)

!F6;#I8 , (plaque-like)

!I; %<*4 (atrophic)

!D?;0#E C, (bullous)

!M<%2 (erosive)

!G< (#F3<#1)5#L;%=!,2L#@A.*/34GA84;%&.*/)?A(>%L#@A$; ,=F9 NO/=$; ,=F9#* C0*L>/% $*&2 P3,B-;, )8#D,+;,&-@2FQ0

(Wickham’s striae)

Lichen planus

Desquamative Gingivitis

!"#$%&'()* +,'-./.&,' 1) R,-B &>/%4?9#, NO/=012HB$;-02142,$9#,D1-+%=

L1 C#)G!#1) N<<S9$>%.*/ $*&2-;, %BF(#'TN@)(acanthosis) F<B $ D$@AHS.*/0*<12JKB(<8,&U1# <>/%& (saw-toothed rete ridges)

2) 2,$ )>/%0+%= 4N1< N<<SF44<@2 (%FU" 2L1#(liquefaction degeneration)

3) 2,$F.$2NO0+%=<@0'UGNDS (lymphocytes)'A& P3,BL#@A.* N<<S (T cell) .*/0*<12JKB !" #FM4 (band-like) .*/4$@ -K5D8D;%L1 C# #> C% &>/%4?6@-

Band-like infiltrate of

T lymphocytes and macrophages

Basal cell degeneration(apoptosis)

Malignant Transformation

!OLP 2142,$ !<*/&#F!<=G! !" #0B $"=#1 C# !" #!$B A"#.*/0*2,$M2 M*&=21#0, !" # -<,#,#!H,22,$.4.-#-$$K2$$034-;,!%1D$,2,$ !<*/&#F!<=G! !" #0B $"=D;%!*

+%= OLP %&7;$B9-;,=$8%&<B 0.04 MO= 1.74


!Holmstrup et al. (1988) D@AD,0 611 (# !" #$B&B -<, P<*/& 7.5 !* 34-;,$%&'$(#* C0*2,$ !<*/&#F!<=G! !" #0B $"=$8%&<B 1.5

!F)A=-;, OLP .E,598678!; -&0*(-,0 )*/&=D;%2,$ !" #0B $"=L;%=!,2)7=0,22-;,!$BL,2$!2D@MO= 50 .;,


! Epstein et al. (2003) VO2J,5#678!; -& 173

(# 'A&&OA 2KWS2,$-@#@HP1&'$( OLP

F<B Lichenoid lesions .*/598'A& WHO

%&;,= ($; =($1A 34-;,$%&'$(5#678!; -& 3

(# (@A !" #$8%&<B 1.7 0*2,$ !<*/&#F!<=G! !" #0B $"=L;%=!,2


!"# $ OLP !"#$%&'%()*+,-./%&0!1.-.2 !'3-4251#678) !"#9: )/%;</3 !"#=/)*

- 8&)>:+-.2 !-?4+3-08&)-'8)*$%&@A+<B!:5C)54)0(47 !"##D5*/:+>'%()*+,1#64D;E0D!@4+0@:),+4*:)'3-425 (carcinogens) 1#6'+**>:+ !"#)8&!

Thank you

Documents

Oral Potentially Malignant Disorders and Cancerdental.anamai.moph.go.th/elderly/2558/Project13-14aug15_03.pdf · Oral Potentially Malignant Disorders and Cancer Anak Iamaroon Professor