understanding oral cancer · references choi sw, thomson p. increasing incidence of oral cancer in...
TRANSCRIPT
Understanding
Oral Cancerin the
Mariana Islands
LAWRENCE L. WILLIAMS, JR., MD
ENT SURGEON
“The views presented in this presentation
are the views of the author and not the
views of DoD or the Navy.”
Contents
Global Impact?
What does it look like?
How do we screen for it?
How do we treat it?
What causes it?
Local Challenges?
Global Impact
5th Most Common Cancer in the World
400,000 new cases a year
95% of all oral cancer is Squamous Cell Carcinoma (SCCa)
Majority of the studies from India, Hong Kong, and Taiwan.
Typically involving tongue and buccal mucosa in Southern/SE Asia and Oceana
Greatest Risk Factors:
Age
Tobacco use
Tobacco + Alcohol
Betel Nut
So, what’s the rub?
Globally over the past 50 years there has been a general trend in prognosis improvement with all cancers.
However, Oral Cancer prognosis, while improved still hasn’t matched the overall trend and it hovers around/above 50%
By the time oral cancers are discovered, they are usually Stage III/IV resulting in a poor prognosis.
What does it look like?
“Oral Potentially Malignant Disorders” (OPMD)
Leukoplakia
Erythroplakia
Oral Submucosal Fibrosis (OSF)
Sialometaplasia
Lupus
Lichen Planus
Oral Cavity Cancer
Squamous Cell Carcinoma (SCCa)
Salivary Gland Tumors
How Do We Screen?
Self examination
Dentist office visits
Primary Care Providers
Specialty Clinics (ENT and Oral Surgery)
How Could We Screen Better?
Focus screening techniques on high
risk groups
Focus on tobacco prevention
Broader community involvement
How Do we Treat?
Oral Potentially Malignant Disorders (OPMD)
Observation vs. Biopsy
Biopsy positive cancer (treat according to NCCN and AJCC)
Medical Interventions (Warnakulasuriya et al., 2016)
Vitamins and Antioxidants
Placental extract (homograft stimulating tissue regeneration)
Proteolytic enzymes
Steroid injections
Vasodilators
How Could We Treat Better?
Increase our coverage as providers
Rocha et al, 2017 : Increasing provider coverage (Family Health Strategy Teams) and $$$ → decreased
mortality over 10 yr period
Ensure we are screening better. The earlier we
catch it, the better the prognosis.
Cancer Staging
National Comprehensive Cancer Network (NCCN) Clinical
Practice Guidelines in Oncology – Head and Neck Cancers
(v.1,2019 - 3/6/2019)
American Joint Committee on Cancer (AJCC), pub 2017
AJCC Cancer Staging Manual, 8th Edition
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Surgical Interventions
Glossectomy +/- Neck Dissection
Reconstruction
Free flap
Pectoralis flap
Composite Resection +/- Neck Dissection
Reconstruction
Free Flap
FAMM Flap
Mandibulectomy +/- Neck Dissection
Reconstruction
Free Flap
Pectoralis flap
Local Challenges with Betel Nut and Tobacco
Betel Nut Chewing
Worldwide v. Local Prevalence
Why is it harmful?
Methods of Use
Teens and Tobacco
What is Betel Nut?
Epidemiology
600 million people worldwide prevalence
4th in worldwide use of psychoactive substances(include: nicotine, alcohol and cannabis)
Most common in India, Taiwan and Melanesia
Also common in Micronesia. Majority of the studies take place in Guam, CNMI, Federated States of Micronesia (FSM) and Republic of Palau and Republic of Marshall Islands.
Clear causal link to oral cancer has been established and well documented in the literature
Why is Betel Nut Harmful?
1987 - International Agency for Research on Cancer
(IARC) concluded “betel quid containing tobacco was
carcinogenic to humans.”
2004 – IARC revised their evaluation that betel quid even
“without tobacco” was carcinogenic. In addition,
areca nut (alone) is carcinogenic.
Evidence in human studies with betel quid +/- tobacco
Evidence in animal studies with areca nut (alone)
Less evidence in any study with betel leaf and slaked lime
Significance
Customs variation in betel nut preparation and consumption within Micronesia and how this variation differs among ethnic communities.
In 2014, “Areca (betel) Nut Chewers’ Health Project” was a crossectional study, n=300, >18yo, Guam and Saipan
Identify patterns from chewing behaviors with a validated questionnaire
2 tier oral screening performed by an Oral Hygienist and Dentist
Results amplified the findings in a 2011 pilot study
2 chewing patterns
2 Styles of Betel Nut Chewing(in the Marianas)
Class 1 Chewers “Chamorro Style”
Ripe areca nut (without quid)
Longer chew
Less often, less nuts
Swallow nut
Class 2 Chewers “Yapese Style”
Unripe areca nut (with quid)
Shorter chew
More often, more nuts
No swallow
Style and Risk
What does this tell us?
Consider focused screening on “Yapese style” chewers.
Mobile Dental Units
Increased training of PCP’s
How though?
How do we target our screening effectively?
How do we maintain compliance and effective followupafter screening?
How do we get patients to stop?
Betel Nut
Cessation Trial
Clinical Trial : NCT02942745
Recruiting since 10/2016 and ends 8/2019 ->18yo Guam or Saipan
2 arms
Experimental: Intensive 5 session intervention program over 22 days and then at 6 months
Placebo: Betel nut cessation booklet
Outcome measures
#self-report quit (after 22 days and then again at 6 months)
Biomarkers in saliva (after 22 days and then again at 6 months)
Betel Nut Prevalence in Guam
What’s the prevalence on Guam?
Worldwide its 10-20%
(Paulino et al, 2017) Aim : pull data from Betel Nut Chewers Pilot Study from (Paulino et al., 2014) and look for trends using national surveillance data in Guam.
Chamorro prevalence decreased from 2011 to 2015
(16.6% - 13%)
However Non-Chamorros doubled (6.6% - 12.5%)
Prevalence – rest of Micronesia…
Betel Nut Prevalence in
Micronesia (excluding the
Marianas) - 2017
N = 1200
First study to report
prevalence across FSM,
Palau, Marshall Islands
42% !!!
Bu-ee!
Bua!
Pugua!
Pu!
Pue!
What’s It called?
Behaviors
Cross-sectional study in Guam (n=30) using a validated survey:“Betel Nut Dependence Scale”
16 questions which were grouped:
Reasons Started
Reasons to Chew
Cultural Importance
Social Importance
Social Acceptance
Reasons to Quit
Methods to Quit
vs.
Addiction with Children
Cross-sectional studies (n=420) among high schoolers in Saipan (1st
Study) compared to Pohnpei and Yap (2nd Study) - 2015
39.1% Saipan chewed
38% Pohnpei chewed
90% + Tobacco
91% Yapese chewed
64% + Tobacco
Dose Response Relationship
Vaping
Vaping may be a gateway to tobacco use especially in new or young users.
Strong association of prior e-cigarette use with cigarette initiation
x8.5 higher than no exposure in low-risk youths
x2 higher than prior other tobacco product use!
Interesting Case
74 year old male aspirated a
betel nut 2 months prior.
Hospitalized for pneumonia
and treated with IV abx.
Setup
Summary
Oral Cancer Prognosis still lags the average among all cancers
Improved screening from all providers
Betel nut prevalence tied to strong cultural/family traditions and through tobacco use
References
Choi SW, Thomson P. Increasing incidence of oral cancer in Hong Kong-Who, where…and why?. J Oral Pathol Med. 2019 May 9;. doi: 10.1111/jop.12868. [Epub ahead of print] PubMed PMID: 31070810.
Tsou HH, Ko HT, Chen CT, Wang TW, Lee CH, Liu TY, Wang HT. Betel quid containing safrole enhances metabolic activation of tobacco specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Environ Pollut. 2019 Apr 30;251:13-21. doi: 10.1016/j.envpol.2019.04.080. [Epub ahead of print] PubMed PMID: 31071628.
Islam S, Muthumala M, Matsuoka H, Uehara O, Kuramitsu Y, Chiba I, Abiko Y. How Each Component of Betel Quid Is Involved in Oral Carcinogenesis: Mutual Interactions and Synergistic Effects with Other Carcinogens-a Review Article. Curr Oncol Rep. 2019 Apr 26;21(6):53. doi: 10.1007/s11912-019-0800-8. Review. PubMed PMID: 31028548.
Jain A, Taneja S. Oral Submucous Fibrosis in Pediatric Patients: A Systematic Review and Protocol for Management. Int J Surg Oncol. 2019;2019:3497136. doi: 10.1155/2019/3497136. eCollection 2019. Review. PubMed PMID: 31057961; PubMed Central PMCID: PMC6463605.
Shi LL, Bradford E, Depalo DE, Chen AY. Betel Quid Use and Oral Cancer in a High-Risk Refugee Community in the USA: The Effectiveness of an Awareness Initiative. J Cancer Educ. 2019 Apr;34(2):309-314. doi: 10.1007/s13187-017-1303-7. PubMed PMID: 29164494.
Franke AA, Biggs L, Yew JY, Lai JF. Areca alkaloids measured from buccal cells using DART-MS serve as accurate biomarkers for areca nut chewing. Drug Test Anal. 2019 Mar 7;. doi: 10.1002/dta.2585. [Epub ahead of print] PubMed PMID: 30845375.
Deshpande S, Radke U, Karemore T, Mohril R, Rawlani S, Ingole P. A Novel Mobile App for Oral Cancer Awareness amongst General Population: Development, Implementation, and Evaluation. J Contemp Dent Pract. 2019 Feb 1;20(2):190-196. PubMed PMID: 31058634.
Chan MH, Wang F, Mang WK, Tse LA. Sex Differences in Time Trends on Incidence Rates of Oropharyngeal and Oral Cavity Cancers in Hong Kong. Ann Otol Rhinol Laryngol.2018 Dec;127(12):895-902. doi: 10.1177/0003489418802287. Epub 2018 Sep 29. PubMed PMID: 30269509.
References
Williams L, Tmanova L, Mydlarz WK, Page B, Richmon JD, Quon H, Schmitt NC.Radiation-Associated Sarcoma of the Neck: Case Series and Systematic
Review. Ann Otol Rhinol Laryngol. 2018 Oct;127(10):735-740. doi: 10.1177/0003489418789966. Epub 2018 Jul 26. Review. PubMed PMID: 30047787.
Lee CY, Wu CF, Chen CM, Chang YY. Qualitative study for betel quid cessation among oral cancer patients. PLoS One. 2018;13(7):e0199503. doi:
10.1371/journal.pone.0199503. eCollection 2018. PubMed PMID: 30016322; PubMed Central PMCID: PMC6049897.
Warnakulasuriya S. Clinical features and presentation of oral potentially malignant disorders. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018
Jun;125(6):582-590. doi: 10.1016/j.oooo.2018.03.011. Epub 2018 Apr 4. Review. PubMed PMID: 29673799.
Faouzi M, Neupane RP, Yang J, Williams P, Penner R. Areca nut extracts mobilize calcium and release pro-inflammatory cytokines from various immune
cells. Sci Rep.2018 Jan 18;8(1):1075. doi: 10.1038/s41598-017-18996-2. PubMed PMID: 29348572; PubMed Central PMCID: PMC5773534.
Rocha TAH, Thomaz EBAF, da Silva NC, de Sousa Queiroz RC, de Souza MR, Barbosa ACQ, Thumé E, Rocha JVM, Alvares V, de Almeida DG, Vissoci JRN,
Staton CA, Facchini LA. Oral primary care: an analysis of its impact on the incidence and mortality rates of oral cancer. BMC Cancer. 2017 Oct
30;17(1):706. doi: 10.1186/s12885-017-3700-z. PubMed PMID: 29084516; PubMed Central PMCID: PMC5661925.
Paulino YC, Hurwitz EL, Ogo JC, Paulino TC, Yamanaka AB, Novotny R, Wilkens LR, Miller MJ, Palafox NA. Epidemiology of areca (betel) nut use in the
mariana islands: Findings from the University of Guam/University of Hawai`i cancer center partnership program. Cancer Epidemiol. 2017 Oct;50(Pt B):241-
246. doi: 10.1016/j.canep.2017.08.006. PubMed PMID: 29120831; PubMed Central PMCID: PMC5747254.
Paulino YC, Ettienne R, Novotny R, Wilkens LR, Shomour M, Sigrah C, Remengesau SD, Johnson EL, Alfred JM, Gilmatam DF. Areca (betel) nut chewing
practices of adults and health behaviors of their children in the Freely Associated States, Micronesia: Findings from the Children's Healthy Living (CHL)
Program. Cancer Epidemiol. 2017 Oct;50(Pt B):234-240. doi: 10.1016/j.canep.2017.07.009. PubMed PMID: 29120830.
Ghantous Y, Abu Elnaaj I. [GLOBAL INCIDENCE AND RISK FACTORS OF ORAL CANCER].Harefuah. 2017 Oct;156(10):645-649. Review. PubMed PMID:
29072384.
Murphy KL, Liu M, Herzog TA. Confirmatory factor analysis and structural equation modeling of socio-cultural constructs among chamorro and non-
chamorro micronesian betel nut chewers. Ethn Health. 2017 Jul 5;:1-12. doi: 10.1080/13557858.2017.1346177. [Epub ahead of print] PubMed PMID:
28678534; PubMed Central PMCID: PMC6013408.
References
Chuang SL, Su WW, Chen SL, Yen AM, Wang CP, Fann JC, Chiu SY, Lee YC, Chiu HM, Chang DC, Jou YY, Wu CY, Chen HH, Chen MK, Chiou ST. Population-based screening
program for reducing oral cancer mortality in 2,334,299 Taiwanese cigarette smokers and/or betel quid chewers. Cancer. 2017 May 1;123(9):1597-1609. doi:
10.1002/cncr.30517. Epub 2017 Jan 5. PubMed PMID: 28055109.
Paré A, Joly A. [Oral cancer: Risk factors and management]. Presse Med. 2017 Mar;46(3):320-330. doi: 10.1016/j.lpm.2017.01.004. Epub 2017 Feb 21. PubMed PMID:
28233703.
Hernandez BY, Zhu X, Goodman MT, Gatewood R, Mendiola P, Quinata K, Paulino YC.Betel nut chewing, oral premalignant lesions, and the oral microbiome. PLoS
One.2017;12(2):e0172196. doi: 10.1371/journal.pone.0172196. eCollection 2017. PubMed PMID: 28225785; PubMed Central PMCID: PMC5321455.
Singhvi A, Joshi A, Bagul N, Bhatia S, Singh G, Gupta R. The Insight for Initiation and Maintenance of Areca nut chewing Habit and its Effects on Oral Health Status among
School Age Population in Western Rajasthan, India. J Clin Diagn Res. 2016 Nov;10(11):ZC15-ZC18. doi: 10.7860/JCDR/2016/21010.8789. Epub 2016 Nov 1. PubMed PMID:
28050496; PubMed Central PMCID: PMC5198449.
Warnakulasuriya S, Kerr AR. Oral submucous fibrosis: a review of the current management and possible directions for novel therapies. Oral Surg Oral Med Oral Pathol Oral
Radiol. 2016 Aug;122(2):232-41. doi: 10.1016/j.oooo.2016.02.020. Epub 2016 Apr 19. Review. PubMed PMID: 27422422.
Kumar M, Nanavati R, Modi TG, Dobariya C. Oral cancer: Etiology and risk factors: A review. J Cancer Res Ther. 2016 Apr-Jun;12(2):458-63. doi: 10.4103/0973-
1482.186696. Review. PubMed PMID: 27461593.
Milgrom P, Tut OK, Gallen M, Mancl L, Spillane N, Chi DL, Ramsay DS. Symptoms with betel nut and betel nut with tobacco among Micronesian youth. Addict Behav. 2016
Feb;53:120-4. doi: 10.1016/j.addbeh.2015.10.011. Epub 2015 Oct 8. PubMed PMID: 26476008.
Murphy KL, Herzog TA. Sociocultural Factors that Affect Chewing Behaviors among Betel Nut Chewers and Ex-Chewers on Guam. Hawaii J Med Public Health. 2015
Dec;74(12):406-11. PubMed PMID: 26668772; PubMed Central PMCID: PMC4675366.
Tareg AR, Modeste NN, Lee JW, Santos HD. Health Beliefs About Tobacco With Betel Nut Use Among Adults in Yap, Micronesia. Int Q Community Health
Educ.2015;35(3):245-57. doi: 10.1177/0272684X15581344. PubMed PMID: 26099155.
Paulino YC, Hurwitz EL, Warnakulasuriya S, Gatewood RR, Pierson KD, Tenorio LF, Novotny R, Palafox NA, Wilkens LR, Badowski G. Screening for oral potentially malignant
disorders among areca (betel) nut chewers in Guam and Saipan. BMC Oral Health. 2014 Dec 11;14:151. doi: 10.1186/1472-6831-14-151. PubMed PMID: 25495475; PubMed
Central PMCID: PMC4292829.
References
Milgrom P, Tut OK, Gilmatam J, Gallen M, Chi DL. Areca use among adolescents in Yap and Pohnpei, the Federated States of Micronesia. Harm Reduct J. 2013 Oct 17;10:26. doi: 10.1186/1477-7517-10-26. PubMed PMID: 24134714; PubMed Central PMCID: PMC3854772.
Paulino YC, Novotny R, Miller MJ, Murphy SP. Areca (Betel) Nut Chewing Practices in Micronesian Populations. Hawaii J Public Health. 2011 Mar;3(1):19-29. PubMed PMID: 25678943; PubMed Central PMCID: PMC4322768.
Chen YJ, Chang JT, Liao CT, Wang HM, Yen TC, Chiu CC, Lu YC, Li HF, Cheng AJ. Head and neck cancer in the betel quid chewing area: recent advances in molecular carcinogenesis. Cancer Sci. 2008 Aug;99(8):1507-14. doi: 10.1111/j.1349-7006.2008.00863.x. Review. PubMed PMID: 18754860.
Lin YS, Jen YM, Wang BB, Lee JC, Kang BH. Epidemiology of oral cavity cancer in taiwan with emphasis on the role of betel nut chewing. ORL J Otorhinolaryngol Relat Spec. 2005;67(4):230-6. doi: 10.1159/000089214. Epub 2005 Oct 25. PubMed PMID: 16254455.
Biolchini F, Pollastri G, Figurelli S, Chiarini L. Carcinogen metabolism, DNA damage repair and oral head and neck squamocellular carcinoma (HNSCC). A review. Minerva Stomatol. 2005 Jul-Aug;54(7-8):405-14. Review. PubMed PMID: 16210999.
Stich HF, Rosin MP, Brunnemann KD. Oral lesions, genotoxicity and nitrosamines in betel quid chewers with no obvious increase in oral cancer risk. Cancer Lett. 1986 Apr;31(1):15-25. PubMed PMID: 3697952.
Nair J, Ohshima H, Friesen M, Croisy A, Bhide SV, Bartsch H. Tobacco-specific and betel nut-specific N-nitroso compounds: occurrence in saliva and urine of betel quid chewers and formation in vitro by nitrosation of betel quid. Carcinogenesis. 1985 Feb;6(2):295-303. doi: 10.1093/carcin/6.2.295. PubMed PMID: 3971493.
Wenke G, Brunnemann KD, Hoffmann D, Bhide SV. A study of betel quid carcinogenesis. IV. Analysis of the saliva of betel chewers: a preliminary report. J Cancer Res Clin Oncol. 1984;108(1):110-3. PubMed PMID: 6746701.
Thank you!
Lawrence L. Williams, Jr., MD
LCDR, MC, USN
ENT Surgeon
Department Head
Otolaryngology - Head and Neck Surgery
Naval Hospital Guam
671-344-9793
“The views presented in this presentation are the
views of the author and not the views of DoD or
the Navy.”