Diagnostic yield of sentinel lymph node biopsy in oral squamous cell carcinoma T1/T2-N0: systematic review and meta-analysis

Me a-Analysis Head and Neck Oncology Diagnos ic yield o sen inel lymph node biopsy in o al squamous cell ca cinoma T1/T2-N0: sys ema ic e iew and me a-analysis M. Mallo Maga in˜os, M. Sua ´ ez Aju ia, X. Ma ichala Mendı ´a, O ´. A ´l a ez-Calde o ´n Iglesias, C.M. Chamo o Pe onacci, A. Ga cı ´a Ga cı ´a, M. Pe ´ ez Saya ´ns: Diagnos ic yield o sen inel lymph node biopsy in o al squamous cell ca cinoma T1/T2-N0: sys ema ic e iew and me a-analysis. In . J. O al Maxillo ac. Su g. 2021; 50: 1271– 1279. ã 2021 The Au ho s. Published by Else ie Inc. on behal o In e na ional Associa ion o O al and Maxillo acial Su geons. This is an open access a icle unde he CC BY-NC-ND license (h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/). M. Mallo Maga in ˜os 1,a , M. Sua ´ ez Aju ia 2,a , X. Ma ichala Mendı ´a 3 , O ´. A ´l a ez-Calde o ´n Iglesias 4,5 , C. M. Chamo o Pe onacci 1,6 , A. Ga cı ´a Ga cı ´a 1,6 , M. Pe ´ ez Saya ´ns 1,6 1 O al Medicine, O al Su ge y and Implan ology Uni , Facul y o Medicine and Den is y, Uni e sidade de San iago de Compos ela, San iago de Compos ela, Spain; 2 O al Medicine Uni , Eu opean Uni e si y o Mad id, Mad id, Spain; 3 Depa men o Nu sing I, Facul y o Medicine and Nu sing, Uni e si y o he Basque Coun y, Basque Coun y, Spain; 4 Depa men o Heal h Sciences, School o Nu sing and Podia y, Uni e si y o Co un ˜a, A Co un ˜a, Spain; 5 O o hinola yngology Se ice o Uni e si y Hospi al o Ou ense, Spain; 6 Ins i u o de In es igacio ´n Sani a ia de San iago (IDIS), San iago de Compos ela, Spain Abs ac . The objec i e o his s udy was o conduc a sys ema ic e iew and me a- analysis on he e icacy o sen inel lymph node biopsy (SLNB) in T1/T2-N0 o al squamous cell ca cinoma (OSCC). A sys ema ic e iew o he li e a u e on SLNB un il Ma ch 2019 was conduc ed. The e iew was o ganized acco ding o he PRISMA p o ocol, conside ing he ollowing PICO (popula ion, in e en ion, compa ison, ou come) ques ion: Wha is he sensi i i y o sen inel lymph node biopsy in OSCC? ‘P’ was pa ien s wi h head and neck squamous cell ca cinoma T1/ 2-N0; ‘I’ was SLNB; ‘C’ was neck ea ed wi h elec i e neck dissec ion and haema oxylin–eosin his opa hology; ‘O’ was sensi i i y and speci ici y. A me a- analysis and me a- eg ession we e pe o med on he selec ed s udies. The sensi i i y o SLNB was up o 88% (95% con idence in e al (CI) 72–96%) and speci ici y was up o 99% (95% CI 96–100%). The a ea unde he summa y ecei e ope a ing cha ac e is ic cu e was 0.99 (95% CI 0.98–1.00). In he ou s udies whe e immunohis ochemis y was pe o med, bo h he sensi i i y and speci ici y we e highe han in he s udies wi hou immunohis ochemis y: 93% (95% CI 88– 97%) and 98% (95% CI 96–100%), espec i ely. In conclusion, SLNB is an e ec i e echnique o ea ing pa ien s wi h some ypes o s age T1/2-N0 OSCC. Some pa ame e s such as immunohis ochemis y could de e mine he le el o diagnos ic accu acy. Key wo ds: sen inel lymph node biopsy; mou h neoplasms; sensi i i y and speci ici y; su i al analysis; sys ema ic e iew. Accep ed o publica ion 27 Janua y 2021 A ailable online 16 Feb ua y 2021 In . J. O al Maxillo ac. Su g. 2021; 50: 1271–1279 h ps://doi.o g/10.1016/j.ijom.2021.01.020, a ailable online a h ps://www.sciencedi ec .com a Manuel Mallo Maga in ˜os and Ma ı´a Sua´ ez Aju ia pa icipa ed equally in he e- sea ch. 0901-5027/01001271 + 09 ã 2021 The Au ho s. Published by Else ie Inc. on behal o In e na ional Associa ion o O al and Maxillo acial Su geons. This is an open access a icle unde he CC BY-NC-ND license (h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/). The incidence o o al cance (354,864 new cases in 2018) inc eases wi h age, and indi iduals o middle o ad anced age de elop o al cance a a highe equency. O al cance has a high mo ali y a e, and i accoun ed o 177,384 dea hs wo ldwide in 2018 1 . The p ima y si e o head and neck squamous cell ca cinoma (HNSCC) a ies conside ably h oughou he wo ld. O all he di e en ypes o malignan umou s ha occu in he o al ca i y, o al squamous cell ca cinoma (OSCC) is he mos p e alen , accoun ing o 90% o all cases 2 . Lymph node in ol emen and he p es- ence o me as asis emain he clinical e e ences o assessing he p ognosis o o al cance . The TNM Classi ica ion o Malignan Tumou s (a globally ecog- nized s anda d o classi ying he ex en o sp ead o cance ) has unde gone se e al e isions o e he yea s due o clinical and scien i ic ad ances. In he eigh h edi ion o he Wo ld Heal h O ganiza ion (WHO) Classi ica ion o Head and Neck Tumou s 3 , se e al impo an pa ame e s we e upda ed, including umou s associ- a ed wi h human papilloma i us and T modi ica ions, by aking in o accoun he dep h o in asion (DOI). In any case, egional lymph node p og ession emains he mos impo an de e mining ac o ha a ec s he speci ic a e o su i al o his disease, and in he case in which nodes a e a ec ed, he su i al a e is educed by up o 50% 4–6 . The ea men o pa ien s who do no p esen clinical o ob ious adiog aphic e idence o egional me as asis (N0) emains con o e sial. Acco ding o Weiss e al. 7 , a pa ien wi h p ima y HNSCC and an N0 neck s a us should be obse ed i he p obabili y o occul ce ical me as a- sis is less han 20%. I he p obabili y is g ea e han 20%, an elec i e neck dissec- ion (END) is wa an ed. Howe e , pe - o ming an END on N0 pa ien s may no be he op imal p ocedu e o assessmen and diagnosis. The sen inel lymph node (SLN) is de- ined as he ini ial node in a lymph node chain ha is a ec ed by he sp ead o a p ima y umou , which is he e o e he closes umou o i . This means ha when a cance in ol es se e al a ec ed nodes, he i s o hese will be he SLN. When a pa ien p esen s wi h a umou o inde ini e size (Tx) and wi h no appa en clinical o adiog aphic e idence o lympha ic in- ol emen (N0), a sen inel lymph node biopsy (SLNB) will p o ide e y use ul in o ma ion o he inal s age o he u- mou 8 . The ad an ages o pe o ming a SLNB ins ead o an END include a de- c eased mo bidi y a e, a educ ion in bo h he ope a i e ime and he du a ion o he pos ope a i e hospi al s ay, and a mo e cos -e ec i e p ocedu e 9 . Se e al p ocesses a e pe o med in o - de o ob ain SLNB da a. The i s s age is explo a ion o he umou , in which a i- ous echniques a e used o iden i y he SLN. Following his, he lymph node is ex ac ed, and inally a biopsy is pe - o med in o de o ob ain p ecise in o ma- ion 10,11 . The mos commonly used diagnos ic ool is Techne ium 99 (Tc99), due o i s easy de ec ion and low gamma adia ion 12 . This echnique is e y use ul o showing he loca ion o he SLN, as well as o de e mining he ea men a ea i any adiologically a ec ed lymph nodes (Tx-N1) appea . The SLNB has been con- side ed a s anda d p ocess o he diagno- sis o s age T1 o T2 OSCC since 2000; howe e , he i s o al cance s udies in which i s high me as a ic de ec ion capac- i y was p o ed we e no epo ed un il a ew yea s la e 13 . The clinical yield o SLNB has been highly a iable in e ms o sensi i i y and speci ici y in he di e en s udies, cen es, and da es o comple ion 14–17 . Many wo ks published wo ldwide ha e compa ed he g ea e ec i eness o his echnique wi h o he mo e con en ional, ye mo e agg es- si e echniques, such as END. The su i - al a e emains e y low, a less han 50% a e 5 yea s o pa ien s wi h ad anced s age umou s, and his is due p edomi- nan ly o delayed diagnosis and dis an me as asis 18 . Al hough se e al me a-anal- yses ha e been conduc ed in o de o assess SLNB in HNSCC, he p esen s udy ocused solely on o al ca i y umou s. The aim o his s udy was o conduc a sys em- a ic e iew o he e iciency o SLNB in exclusi ely T1/T2-N0 umou s o he o al ca i y and o pe o m a me a-analysis o he s udies mee ing he inclusion c i e ia. Seconda y objec i es we e (1) o desc ibe in de ail he esul s ob ained in he s udies included in he sys ema ic e iew, and (2) o analyse he e icacy and clinical pe o - mance o SLNB using da a such as sensi- i i y and su i al. Me hods P o ocol and eligibili y c i e ia A sys ema ic e iew o a icles published in he li e a u e be ween Janua y 1, 2000 and Ma ch 31, 2019 was conduc ed in he Uni o O al Medicine, O al Su ge y and Implan ology o he Facul y o Medicine and Den is y, Uni e si y o San iago de Compos ela. This sys ema ic e iew was egis e ed in PROSPERO on Augus 7, 2019 ( e e ence CRD42019120157). The e iew was o ganized acco ding o he PRISMA p o ocol 19 , conside ing he ol- lowing PICO (popula ion, in e en ion, compa ison, ou come) ques ion: Wha is he sensi i i y o sen inel lymph node biopsy in OSCC? ‘P’ was pa ien s wi h head and neck squamous cell ca cinoma T1/2-N0; ‘I’ was SLNB; ‘C’ was neck ea ed wi h END and haema oxylin–eosin (H&E) his opa hology; ‘O’ was sensi i i y and speci ici y. Sou ces This s udy used he Rayyan QCRI sys em- a ic e iew suppo pla o m (Qa a Com- pu ing Resea ch Ins i u e (Da a Analy ics), Doha, Qa a ) 20 , which allows o ex ensi e online and collabo a i e bib- liog aphic sea ches. The keywo ds and medical subjec heading (MeSH) e ms used we e: ‘‘Sen inel Lymph Node Biop- sy’’, ‘‘O al Cance ’’, ‘‘O al Tumou ’’, ‘‘Mou h Neoplasms’’ and ‘‘O al Squa- mous Cell Ca cinoma’’. Fo e i ica ion pu poses, he ollowing we e elec onical- ly sea ched: MEDLINE ( h ough PubMed), Embase ( h ough OVID), Web o Science, Scopus, Coch ane Li- b a y, ClinicalT ials.go , he i e WHO egional bibliog aphic da abases (AIM, LILACS, IMEMR, IMSEAR, WPRIM), and he Con e ence P oceedings Ci a ion Index. This p ocess was supplemen ed by manual sea ches o a se ies o pee - e iewed jou nals con aining ela ed con- en . Po en ially ele an a icles known o any o he au ho s we e sea ched, and likewise, e e ence lis s om he e ie ed e iew a icles we e also exhaus i ely checked. S udy selec ion and da a ex ac ion p ocess The sea ch was conduc ed h ough he Rayyan QCRI pla o m by h ee obse e s (MSA, MMM, and OAC); a ou h obse - e (MPS) was consul ed in he case o any disag eemen . The eligibili y c i e ia o he e ie ed s udies we e (1) (a) pa ien s wi h HNSCC (only o al ca i y), (b) pa ien s wi h T1/2-N0, (c) pa ien s man- aged wi h SLNB, (d) pa ien s wi h a ol- low-up pe iod o longe han 12 mon hs; (2) a icles published a e 2000; (3) da a on alse-nega i es, sensi i i y, speci ici y, and su i al. The exclusion c i e ia we e s udies including T3 umou s, case epo s, le e s, abs ac s, sys ema ic e iews, and ex s in languages o he han English. In he i s ound, he i le and 1272 Mallo Maga in˜os e al. abs ac o he e ie ed a icles we e ead and any s udies ha me he inclusion c i e ia o did no p o ide su icien da a in o de o a clea decision o be made ega ding hei inclusion we e subsequen - ly examined in ull ex . In he second ound, all o he s udies ha we e consid- e ed eligible unde wen ull- ex sc eening and a inal decision was made ega ding hei inclusion in he s udy. Da a we e ex ac ed usinga s anda dized, pilo - es ed o m. This o m included he ollowing i ems: i le (o iginal i le o he e iewed publica ion); au ho s ( hose who pa icipa ed in he publica ion); yea (yea in which he a icle was published); sample (numbe o indi iduals who had aken pa since he beginning o he s udy); Tx (num- be o pa ien s wi h T1 o T2, excluding lesions wi h in si u ca cinoma); di e en ia- ion (deg ee o his opa hological di e en- ia ion: (a) well-di e en ia ed, (b) mode a ely di e en ia ed, o (c) undi e - en ia ed); su gical ma gins (posi i e ma - gins on umou excision); neck le els (loca ion in he neck o node(s)); emo ed lymph nodes (LN) (numbe o nodes ha we e emo ed in all o he sample); posi i e lymph nodes (LN+); nega i e lymph nodes (LN); ollow-up ime (a e age numbe o mon hs ha he s udy pa ien s we e ol- lowed-up o ); alse-nega i es (FN) (pa ien s who we e diagnosed wi h nega i e nodal in ol emen bu who subsequen ly had in ol emen in a leas one lymph node); posi i e p edic i e alue (PPV) ( he p obabili y o ha ing nodal in ol e- men when he SLNB was posi i e); ue- nega i es (TN) (pa ien s who we e diag- nosed wi h nega i e nodal in ol emen and who had no in ol emen ); nega i e p edic- i e alue (NPV) ( he p obabili y ha sub- jec s wi h nega i e nodal in ol emen uly do no ha e he disease); mac ome as asis ( he numbe o nodes wi h a leas one me as asis >2 mm); mic ome as asis; iso- la ed umou cells; sensi i i y (p obabili y wi h which he SLNB is able o iden i y pa ien s wi h some LN+); speci ici y (p ob- abili y wi h which he SLNB iden i ies neg- a i e pa ien s om he sample o heal hy pa ien s); dea h (pa ien s who died be o e he end o he s udy); a e age su i al (pa ien s who we e s ill ali e a he end o he s udy); disease-speci ic su i al in LN+ pa ien s (DSSN+) (p opo ion o LN+ pa ien s who we e s ill ali e a he end o hes udy); disease-speci ic su i al in LN pa ien s (DSSN) (p opo ion o LN pa ien s who we e s ill ali e a he end o he s udy); elapse (pa ien s wi h ecu - ences in he p ima y umou si e o in some node); disease- ee su i al in SLN+ pa ien s (DFSN+) (p opo ion o pa ien s wi hou any sign o disease wi h posi i e SLNB esul s); disease- ee su i al in SLN pa ien s (DFSN) (p opo ion o pa ien s wi hou signs o disease who we e LN in he SLNB). Risk o bias assessmen , da a syn hesis, and analysis The me hodological quali y o he included s udies and he possibili y o bias we e assessed using he Newcas le–O awa scale (NOS) o coho s udies 21 and he QUA- DAS-2 ool, which is a ool o assess he quali y o diagnos ic p ecision s udies 22 . The au ho s o he NOS ecommend e alu- a ing he quali y o he s udy acco ding o h ee ca ego ies: selec ion ( ou ques ions, maximum possible sco e 4 s a s), compa a- bili y (one ques ion, maximum possible sco e 2 s a s),and ou come( h eeques ions, maximum possible sco e 3 s a s), gi ing a low quali y alue (1–3 s a s), medium qual- i y alue (4–6 s a s), o high quali y alue (7–9 s a s). This analysis was conduc ed independen ly by wo esea che s (MSA and OAC), and in he case o any disag ee- men , a hi d esea che (MPS) ac ed as he media o . The QUADAS-2 ool was used o Diagnos ic yield o SLNB in OSCC T1/T2-N0 1273 Fig. 1. Flow cha o he sys ema ic e iew. assess he s udies selec ed o me a-analy- sis. This ool consis s o ou domains: (1) pa ien selec ion, (2) index es , (3) e e - ence es , and (4) low and iming. Each domain is e alua ed in e ms o i s isk o bias, and he i s h ee domains a e also e alua ed in e ms o hei applicabili y. All o he a iables we e collec ed in a da abase and we e analysed wi h IBM SPSS S a is ics o Windows e sion 24.0 (IBM Co p., A monk, NY, USA). The a iables we e desc ibed using he equency, pe cen age, mean, and s anda d de ia ion. Fo he a icles ha we e in- cluded in he sys ema ic e iew, he a e - age da a, minimum alue, maximum alue, s anda d de ia ion, and he o al numbe o a icles in which he in o ma- ion was p o ided we e calcula ed. De i ed logi es ima es o sensi i i y, speci ici y, and espec i e a iances we e used o cons uc a hie a chical summa y ecei e ope a ing cha ac e is ic (SROC) cu e. The da a ex ac ion o he me a- analysis was pe o med by wo esea ch- e s (XMM and MPS). The ex ac ed da a included he au ho and yea o publica- ion, and 2  2 ables o ue-posi i es (TP), ue-nega i es (TN), alse-posi i es (FP), and alse-nega i es (FN) in o de o calcula e he sensi i i y and speci ici y. In he me a-analysis, he da a we e an- alysed wi h he MIDAS module (Me a- Analy ical In eg a ion o Diagnos ic Ac- cu acy S udies) using S a a 16 so wa e (S a aCo p, College S a ion, TX, USA). To assess he he e ogenei y among s ud- ies, he Q-s a is ic and I 2 alue we e cal- cula ed. A P- alue o <0.10 and I 2 >50% indica ed conside able he e ogenei y be- ween s udies, and he andom-e ec s model was conduc ed; o he wise, he ixed-e ec s model was used. The da a we e u he analysed using a me a- eg es- sion analysis using s udy co a ia es, s a - i ying he esul s by SLN pa hology me hod (immunohis ochemis y (IHC) o no , sec ional se ies o no ), ype o e e - ence es (neck dissec ion o ollow-up), and s udy design (p ospec i e o e o- spec i e) in iew o he g ea e e ec o di e en s udy cha ac e is ics on he diag- nos ic e icacy o SLNB, and o explo e he sou ces o be ween-s udy he e ogene- i y. All bila e al di e ences wi h a P- alue o 0.05 we e conside ed as signi ican . Resul s A low diag am o he a icle selec ion p ocess is gi en in Fig. 1. A o al o 411 a icles we e iden i ied in he i s sea ch. A e he i s e iew, which was pe - o med by h ee e alua o s, 346 a icles 1274 Mallo Maga in˜os e al. Fig. 2. Resul s o QUADAS-2: isk o bias and conce ns ega ding applicabili y. (84.2%) we e excluded, and 54 included a icles (13.1%) and 11 dispu ed a icles (2.7%) we e ob ained. A e eading he ull ex s, nine o he ini ially accep ed a icles and se en o he dispu ed a icles we e disca ded, esul ing in a inal o al o 42 included a icles (10.2%) 14–17,23–60 . In he quali y assessmen o included a icles acco ding o he NOS scale, one (2.4%) was a ed as low quali y, 21 (50%) as medium quali y, and 20 (47.6%) as high quali y (Supplemen a y Ma e ial Table S1). The quali y assessmen o he a icles included in he me a-analysis (n = 7) acco ding o he QUADAS-2 ool is shown in Fig. 2. The g aph in Fig. 2 shows ha all o he included s udies we e o mode a ely high quali y. The isk o bias wi h ega ds o pa ien selec ion was high in h ee (42.9%) o he s udies, mos ly due o hei e ospec i e na u e, wi hou a consecu i e o andom sample en olmen o pa ien s. The isk o bias ega ding he index es was unclea in wo (28.6%) s udies, high in one (14.3%) s udy, and low in ou (57.1%) s udies. In con as , he e e ence s anda d was unclea in h ee (42.9%) o he s udies. Fo isk o bias in low and iming, i e (71.4%) o he s ud- ies we e conside ed o be o unclea isk. The e was less conce n ega ding he ap- plicabili y o he s udies. The e we e no conce ns abou applicabili y ega ding pa- ien selec ion and he e e ence es in se en (100%) o he s udies, while only wo (28.6%) s udies showed a high isk because o he index es . Tables S2 and S3 in he Supplemen a y Ma e ial epo all o he s udy a iables in he a icles ha we e selec ed o sys- ema ic e iew. A o al o se en s udies wi h 457 pa ien s we e included in he me a-analy- sis 16,26,27,33,34,37,47 . The eligibili y o he a icles was de e mined by he da a p o- ided in each a icle. In o de o an a icle o be included, i had o epo a leas h ee o he ou indexes: ue-posi i es, ue- nega i es, alse-nega i es, and alse-posi- i es, as well as he sensi i i y and speci- ici y alues. The pooled sensi i i y o SLNB was 88% (95% con idence in e al (CI) 72– 96%) and he pooled speci ici y was 99% (95% CI 96–100%) (Fig. 3). The a ea unde he SROC cu e (AUC) was 0.99 (95% CI 0.98–1.00) (Fig. 4). The PPV was 0.98 (95% CI 0.97–0.99) and he NPV was 0.88 (95% CI 0.87–0.89) (Fig. 5). Sensi- Diagnos ic yield o SLNB in OSCC T1/T2-N0 1275 Fig. 3. Fo es plo s o pooled sensi i i y and speci ici y. Fig. 4. Summa y ecei e ope a ing cha ac e is ic (SROC) cu e. i i y was he only pa ame e ha showed an I 2 >50%, he e o e sugges ing consid- e able he e ogenei y. By pe o ming a lea e-one-ou me a-analysis, i was ob- se ed ha by elimina ing he wo k o Al-Dam e al. 16 , he he e ogenei y o he me a-analysis o sensi i i y d opped o 0.49 (95% CI 0.01–0.96), gi ing a sensi- i i y alue o 91% (95% CI 79–96%). The me a- eg ession analysis showed ha he IHC co a ia e was he mos im- po an sou ce o he e ogenei y. A sub- g oup analysis was pe o med o assess di e ences in diagnos ic accu acy using he IHC co a ia e. In he ou s udies whe e IHC was pe o med, bo h he sen- si i i y and speci ici y we e high: 93% (95% CI 88–97%) and 98% (95% CI 96–100%), espec i ely. Howe e , in he h ee s udies whe e IHC was no pe - o med, he sensi i i y was low, al hough he speci ici y was high: 65% (95% CI 47– 84%) and 100% (95% CI 100–100%), espec i ely. The o he co a ia es did no show s a is ically signi ican di e - ences (Table 1). Discussion The SLNB is a key ac o in he pa ien ’s p ognosis. On he one hand, pe o ming a lymph node dissec ion in o de o emo e all o he lympha ic chains in he neck is no necessa y, he e o e educing pa ien mo bidi y 61 , and on he o he hand, as a ela i ely new echnique, he SLNB p o- duces e y e ec i e esul s in ce ain cance s such as b eas cance and melano- ma 62 . This echnique was ex apola ed o use in o al cance ; howe e i p oduced di e en esul s, as shown in he a icles ha we e included in his sys ema ic e- iew. Wi h ega d o sensi i i y, he diagnos- ic capaci y o he SLNB in sick pa ien s will be app ecia ed, i.e. a e y sensi i e es will be e y e ec i e. In his me a- analysis, he a e age sensi i i y eached 88%, howe e i a ied om 50% o 100%, he e o e yielding mixed esul s. The s udies by He nando e al. 14 and Al- Dam e al. 16 bo h ob ained a sensi i i y o 50% in a sample o 73 and 20 pa ien s, espec i ely, and hese da a sugges ha he SLNB should no be p oposed as a ou ine echnique. On he o he hand, se - e al a icles epo ed a sensi i i y o 100% o SLNB, including Ch is ensen e al. 15 and Bu cia e al. 17 , wi h a sample o 51 and 50 pa ien s, espec i ely, ob aining no alse-nega i es. On he o he hand, Schil- ling e al. 40 ob ained a sensi i i y o 86% wi h a conside able sample size o 415 pa ien s, demons a ing esul s e y close o hose a ained in his e iew. The a e age su i al should be he key ac o when deciding whe he o use END o SLNB in pa ien s wi h T1/T2-N0 umou s. P e ious esul s ha e been di- e se depending on he ype o su i al s udied. The e o e, in his e iew, da a on a e age su i al, DSSN+, DSSN, DFSN +, and DFSN we e a iable, especially when conside ing ha in cases o LN+ pa ien s he esul was lowe . The lowes su i al a e was eco ded in he wo k o Moya-Plana e al. 30 , who epo ed an a - e age su i al o 77.3% in a o al sample o 229 pa ien s. This is in con as o o he a icles, which epo ed su i al eaching 100%, such as he s udies by S oeckli e al. 32 and Heu eling e al. 59 . Te ada e al. 57 epo ed a DSSN+ o jus 57.1%, a esul di e ing conside ably om he mean DSSN o 96.60%. He nando e al. 14 ob ained a DSSN o 86%, and despi e being he a icle wi h he lowes DSSN pe cen age, hey demons a ed ha when a pa ien is diagnosed by means o SLNB and he esul s a e nega i e, he pa ien ’s p ognosis imp o es conside - ably. The DFSN+ da a di e ed om he da a ob ained by B oglie e al. 48 in which only 73% o subjec s wi h posi i e SLNB esul s we e disease- ee, a om he 92% achie ed in he s udy by Schilling e al. 40 . Fo he DFSN, he esul s a ied om Flach e al. (72.0%) 39 , bu we e lowe han he 97.2% ob ained by Ionna e al. 55 . App oxima ely 20–30% o p ima y OSCCs ha e some occul nodal me as a- sis, which can be iden i ied by SLNB o END. Nodal dissec ion is a much mo e agg essi e echnique; howe e , i is e y e ec i e in con olling me as asis in N1 pa ien s, al hough i has a g ea e impac on pa ien s in compa ison wi h mo e con- se a i e echniques such as SLNB. Nodal dissec ion o en leads o he o e ea men o pa ien s, esul ing in pos ope a i e con- sequences, wi h he mos equen being dec eased unc ionali y a he shoulde le el, lymphedema, and pos ope a i e sca s 9 . As has al eady been demons a ed, 1276 Mallo Maga in˜os e al. Fig. 5. P obabili y modi ying plo . Table 1. Me a- eg ession analysis o he di e en iden i ied co a ia es. Pa ame e Ca ego y S udies, n Sensi i i y (95% CI) P- alue Speci ici y (95% CI) P- alue S udy design Re ospec i e 2 86% (62–100%) 0.94 98% (95–100%) 0.23 P ospec i e 5 91% (78–100%) 100% (98–100%) IHC/se ial sec ion Yes 4 93% (88–97%) 0.19 98% (96–100%) <0.001 No 3 65% (47–84%) 100% (100–100%) Re e ence es Follow-up 2 92% (81–100%) 0.41 98% (96–100%) 0.88 END 5 86% (70–100%) 99% (97–100%) CI, con idence in e al; IHC, immunohis ochemis y; END, elec i e neck dissec ion. SLNB p oduces mo e han accep able clinical esul s, wi h a educ ion in he a o emen ioned consequences. He nando e al. 14 compa ed he di e en complica- ions ha occu ollowing bo h SLNB p ocedu es and nodal dissec ion o he neck. Thei esul s showed g ea e pain, less shoulde mobili y, g ea e sca ing, and mo e neck haemo hages when he la e was pe o med. In he s udy by Go e s e al. 63 , quali y o li e was e alu- a ed in di e en g oups: unde su eil- lance, SLNB, sup aomohyoid neck dissec ion, and modi ied adical dissec- ion. The quali y o li e o pa ien s who unde wen he SLNB p ocedu e was highe , and likewise hey expe ienced less discom o han hose who unde wen dis- sec ion, especially modi ied adical dis- sec ion. The e a e a numbe o ac o s ha de- e mine he a iabili y in he diagnos ic pe o mance alues o SLNB: wo k cen- e, ype o umou sample (head and neck cance o only OSCC om he o al ca i- y), ollow-up pe iod, da e o publica ion o he s udy, and he pe o mance o se ial SLN cu s wi h o wi hou IHC. Acco ding o Liu e al. 64 , he subg oup analysis based on IHC indica ed ha H&E s aining com- bined wi h IHC was signi ican ly mo e sensi i e han he esul s ob ained when H&E s aining was pe o med on i s own, wi h a sensi i i y o 88% (95% CI 86– 90%) e sus 77% (95% CI 68–85%). Fu - he mo e, he ea ly publica ion subg oup (2000 o 2008) had a be e combined sensi i i y han he la e publica ion sub- g oup (2009 o 2016): 92% (95% CI 87– 95%) e sus 86% (95% CI 83–88%). The p esen s udy con i med simila esul s, ob aining be e esul s in he IHC sub- g oup. In conclusion, SLNB has eme ged as a ela i ely no el echnique o de e mining nodal in ol emen in ce ain cance s such as o al cance . Wi h he in o ma ion p o- ided by his e iew, sen inel node biopsy appea s o be an e ec i e echnique o ea ing pa ien s wi h OSCC in s age T1/2- N0. SLNB eached a sensi i i y o 88% and a speci ici y o 99% in he me a- analysis. Some pa ame e s such as IHC could de e mine he le el o diagnos ic accu acy. Compe ing in e es s The e a e no compe ing in e es s. Funding This esea ch did no ecei e any unding. E hical app o al This a icle is exemp om app o al by he e hics commi ee. Pa ien consen No applicable. S a emen o con i m All he au ho s ha e iewed and ag eed o he submission Appendix A. Supplemen a y da a Supplemen a y ma e ial ela ed o his a icle can be ound, in he online e sion, a doi:h ps://doi.o g/10.1016/j.ijom.2021. 01.020. Re e ences 1. B ay F, Fe lay J, Soe joma a am I, Siegel RL, To e LA, Jemal A. Global cance s a is ics 2018: GLOBOCAN es ima es o incidence and mo ali y wo ldwide o 36 cance s in 185 coun ies. CA Cance J Clin 2018;68:394–424. 2. Muppa apu M, Shan i RM. E alua ion and s aging o o al cance . Den Clin No h Am 2018;62:47–58. 3. Huang SH, O’Sulli an B. O e iew o he 8 h edi ion TNM Classi ica ion o Head and Neck Cance . Cu T ea Op ions Oncol 2017;18:40. 4. Sopik V, Sun P, Na od SA. P edic o s o ime o dea h a e dis an ecu ence in b eas cance pa ien s. B eas Cance Res T ea 2019;173:465–74. 5. Suen JY, Goep e H. S anda diza ion o neck dissec ion nomencla u e. Head Neck Su g 1987;10:75–7. 6. Som PM, Cu in HD, Mancuso AA. An imaging-based classi ica ion o he ce ical nodes designed as an adjunc o ecen clini- cally based nodal classi ica ions. A ch O o- la yngol Head Neck Su g 1999;125:388–96. 7. Weiss MH, Ha ison LB, Isaacs RS. Use o decision analysis in planning a managemen s a egy o he s age N0 neck. A ch O ola - yngol Head Neck Su g 1994;120:699–702. 8. Meh a V, Na han CA. Wha is he ole o sen inel lymph node biopsy in ea ly-s age o al ca i y ca cinoma? La yngoscope 2016;126:9– 10. 9. Mu e K, Hube GF, Haile SR, S oeckli SJ. Compa ison o mo bidi y be ween sen inel node biopsy and elec i e neck dissec ion o ea men o he N0 neck in pa ien s wi h o al squamous cell ca cinoma. Head Neck 2011;33:1260–4. 10. Moncayo VM, Alaz aki AL, Alaz aki NP, Aa s old JN. Sen inel lymph node biopsy p ocedu es. Semin Nucl Med 2017;47:595– 617. 11. Guo J, Yang H, Wang S, Cao Y, Liu M, Xie F, Liu P, Zhou B, Tong F, Cheng L, Liu H, Wang S. Compa ison o sen inel lymph node biopsy guided by indocyanine g een, blue dye, and hei combina ion in b eas cance pa ien s: a p ospec i e coho s udy. Wo ld J Su g Oncol 2017;15:196–7. 12. Su asi DS, O’Malley J, Bhambh ani P. 99mTc-Tilmanocep : a no el molecula agen o lympha ic mapping and sen inel lymph node localiza ion. J Nucl Med Tech- nol 2015;43:87–91. 13. Sha ma D, Koshy G, G o e S, Sha ma B. Sen inel lymph node biopsy: a new ap- p oach in he managemen o head and neck cance s. Sul an Qaboos Uni Med J 2017;17:e3–10. 14. He nando J, Villa eal P, A ´l a ez-Ma cos F, Ga cı ´a-Consueg a L, Gallego L, Junque a L. Sen inel node biopsy e sus elec i e neck dissec ion. Which is mo e cos -e ec i e? A p ospec i e obse a ional s udy. J C anio- maxillo ac Su g 2016;44:550–6. 15. Ch is ensen A, Bilde A, The kildsen MH, Mo ensen J, Cha abi B, Ki kegaa d J, Spech L, on Buchwald C. The p e alence o occul me as ases in nonsen inel lymph nodes a e s ep-se ial sec ioning and immu- nohis ochemis y in cN0 o al squamous cell ca cinoma. La yngoscope 2011;121:294–8. 16. Al-Dam A, P ech C, Ba be A, Kohlmeie C, Hanken H, Wikne J, Scho ¨n G, Heiland M, Assa AT. Sensi i i y and speci ici y o sen- inel lymph node biopsy in pa ien s wi h o al squamous cell ca cinomas using indocya- nine g een luo escence imaging. J C anio- maxillo ac Su g 2018;46:1379–84. 17. Bu cia V, Cos es V, Faillie JL, Ga dine Q, de Ve bizie D, Ca ie C, Jouzdani E, C ampe e L, Gue ie B, Ga el R. Neck es aging wi h sen inel node biopsy in T1–T2N0 o al and o opha yngeal cance : why and how? O ola - yngol Head Neck Su g 2010;142:592–7.e1. 18. Ding D, S okes W, Eguchi M, Ha a ah M, Sumne W, Amini A, Godda d J, Some se H, B adley C, McDe mo J, Raben D, Ka am SD. Associa ion be ween lymph node a io and ecu ence and su i al ou comes in pa ien s wi h o al ca i y cance . JAMA O o- la yngol Head Neck Su g 2019;145:53–61. 19. Libe a i A, Al man DG, Te zla J, Mul ow C, Gø zsche PC, Ioannidis JP, Cla ke M, De e eaux PJ, Kleijnen J, Mohe D. The PRISMA s a emen o epo ing sys ema ic e iews and me a-analyses o s udies ha e alua e heal hca e in e en ions: explana- ion and elabo a ion. BMJ 2009;339:b2700. 20. Ouzzani M, Hammady H, Fedo owicz Z, Elmaga mid A. Rayyan—a web and mobile app o sys ema ic e iews. Sys Re 2016;5:210. 21. Wells G, Shea B, O’Connell DL, Pe e son J, Welch V, Losos M, Tugwell P. The Newcas le–O awa Scale (NOS) o asses- sing he quali y o non andomised s udies in Diagnos ic yield o SLNB in OSCC T1/T2-N0 1277 me a-analyses. O awa Hospi al Resea ch Ins i u e; 2014. 22. Ciapponi A. QUADAS-2: ins umen o pa a la e aluacio ´n de la calidad de es udios de p ecisio ´n diagno ´s ica. [QUADAS-2: an in- s umen o he e alua ion o he quali y o diagnos ic p ecision s udies]. EVIDENCIA – Ac ualizaciœn P A ˜c ica Ambula o ia 2015;18:22–6. 23. Hi aki A, Fukuma D, Naga a M, Shi aishi S, Kawaha a K, Ma suoka Y, Nakagawa Y, Yoshida R, Tanaka T, Yoshi ake Y, Shinoha a M, Yamashi a Y, Nakayama H. Sen inel lymph node biopsy educes he incidence o seconda y neck me as asis in pa ien s wi h o al squamous cell ca cinoma. Mol Clin Oncol 2016;5:57–60. 24. Alku eishi LW, Ross GL, Shoaib T, Sou a DS, Robe son AG, Thompson R, Hun e KD, So ensen JA, Thomsen J, K ogdahl A, Al a ez J, Ba bie L, San ama ia J, Poli T, Sesenna E, Ko a ´cs AF, G u ¨nwald F, Ba zan L, Sul a o S, Albe i F. Sen inel node biopsy in head and neck squamous cell cance : 5- yea ollow-up o a Eu opean mul icen e ial. Ann Su g Oncol 2010;17:2459–64. 25. Gallegos-He na ´ndez JF, He na ´ndez-He na ´n- dez DM, Flo es-Dı ´az R, Sie a-San ies eban I, Picha do-Rome o P, A ias-Ceballos H, Minau o-Mun ˜oz G, Al a ado-Cab e o I. The numbe o sen inel nodes iden i ied as p ognos ic ac o in o al epide moid cance . O al Oncol 2005;41:947–52. 26. Abdul-Razak M, Chung H, Wong E, Palme C, Veness M, Fa low D, Coleman H, Mo gan G. Sen inel lymph node biopsy o ea ly o al cance s: Wes mead Hospi al expe ience. ANZ J Su g 2017;87:65–9. 27. Pezie T, Nixon IJ, Gu ney B, Schilling C, Hussain K, Lyons AJ, Oakley R, Simo R, Jeannon JP, McGu k M. Sen inel lymph node biopsy o T1/T2 o al ca i y squamous cell ca cinoma—a p ospec i e case se ies. Ann Su g Oncol 2012;19:3528–33. 28. an de Linden N, Flach GB, de B ee R, Uyl- de G oo CA. Cos -u ili y o sen inel lymph node biopsy in cT1–T2N0 o al cance . O al Oncol 2016;53:20–6. 29. Holden AM, Sha ma D, Schilling C, Gna- nasega an G, Odell EW, Sassoon I, McGu k M. Biopsy o he sen inel lymph node in o al squamous cell ca cinoma: analysis o e o in 100 consecu i e cases. B J O al Max- illo ac Su g 2018;56:615–20. 30. Moya-PlanaA, Aupe ´ in A,Gue lainJ, Go phe P, Casi aghi O, Mamelle G, Melkane A, Lum- b oso J, Jano F, Temam S. Sen inel node biopsy in ea ly o al squamous cell ca cino- mas: long- e m ollow-up and nodal ailu e analysis. O al Oncol 2018;82:187–94. 31. Boe e K, Schepman KP, Schuu ing E, Roo- denbu g JLN, Halmos GB, an Dijk BAC, Boo sma RAC, de Vissche JGAM, B ouwe s AH, an de Veg B, Wi jes MJH. High sensi i i y and nega i e p edic- i e alue o sen inel lymph node biopsy in a e ospec i e ea ly s age o al ca i y cance coho in he No he n Ne he lands. Clin O ola yngol 2018. Ma 25. 32. S oeckli SJ, Huebne T, Hube GF, B oglie MA. Technique o eliable sen inel node biopsy in squamous cell ca cinomas o he loo o mou h. Head Neck 2016;38:1367–72. 33. Riese CGU, Ka s ad JA, Sch amm A, Gu ¨le - yu ¨z S, D essel G, Lo enz KJ, Klemenz B, Saile A, Sei z S, Wilde F. Validi y o sen i- nel node biopsy in ea ly o al and o opha yn- geal ca cinoma. J C aniomaxillo ac Su g 2018;46:1748–52. 34. Sagheb K, Sagheb K, Rahimi-Nedja R, Taylo K, Al-Nawas B, Wal e C. Sen inel lymph node biopsy in T1/T2 squamous cell ca cinomas o he ongue: a p ospec i e s udy. Oncol Le 2016;11:600–4. 35. Meh a V, Na han C. Wha is he ole o sen inel lymph node biopsy in ea ly-s age o al ca i y ca cinoma? La yngoscope 2016;126:9–10. 36. Chung MK, Lee GJ, Choi N, Cho J, Jeong H, Baek C. Compa a i e s udy o sen inel lymph node biopsy in clinically N0 o al ongue squamous cell ca cinoma: long- e m oncologic ou comes be ween alida ion and applica ion phases. O al Oncol 2015;51:914–20. 37. Pede sen NJ, Jensen DH, Hedba ¨ck N, F endø M, Kiss K, Lelkai is G, Mo ensen J, Ch is- ensen A, Spech L, on Buchwald C. S ag- ing o ea ly lymph node me as ases wi h he sen inel lymph node echnique and p edic- i e ac o s in T1/T2 o al ca i y cance : a e ospec i e single-cen e s udy. Head Neck 2016;38(Suppl 1):1033. 38. Ramamu hy R, Ko ayasamy Seeni asa- gam R, Shanmugam S, Palani elu K. A p ospec i e s udy on sen inel lymph node biopsy in ea ly o al cance s using me hy- lene blue dye alone. Indian J Su g Oncol 2014;5:178–83. 39. Flach GB, Bloemena E, Klop WM, an Es RJ, Schepman KP, Hoeks a OS, Cas elijns JA, Leemans CR, de B ee R. Sen inel lymph node biopsy in clinically N0 T1–T2 s aged o al cance : he Du ch mul icen e ial. O al Oncol 2014;50:1020–4. 40. Schilling C, S oeckli SJ, Hae le SK, B oglie MA, Hube GF, So ensen JA, Bakhold V, K ogdahl A, on Buchwald C, Bilde A, Seb- besen LR, Odell E, Gu ney B, O’Dohe y M, de B ee R, Bloemena E, Flach GB, Villa eal PM, F esno Fo celledo MF, Junque a Gu ie ´ - ez LM, Ame ´zaga JA, Ba bie L, San ama ı ´a- Zuazua J, Mo ei a A, Jacome M, Vigili MG, Rahimi S, Ta aglione G, Lawson G, Nolle- aux MC, G andi C, Donne D, B agan ini E, Dequan e D, Lo hai e P, Poli T, Silini EM, Sesenna E, Doli e G, Mas onicola R, Le oux A, Sassoon I, Sloan P, McGu k M. Sen inel Eu opean Node T ial (SENT): 3-yea esul s o sen inel node biopsy in o al cance . Eu J Cance 2015;51:2777–84. 41. Saba e ´-Llobe a A, Benı ´ ez-Segu a A, Ma ı ´ A, A anz C, Baje ´n MT, Maymo ´-Ga ido S, Ma ı ´n-Comı ´n J. Lymphoscin ig aphy in o al squamous cell ca cinoma sen inel node biopsy and i s ole in he su gical planning. Clin Nucl Med 2014;39:142. 42. Saman S. Sen inel node biopsy as an al e - na i e o elec i e neck dissec ion o s aging o ea ly o al ca cinoma. Head Neck 2014;36:241–6. 43. Den Toom IJ, Heu eling DA, Flach GB, an Wee S, Ka agozoglu KH, an Schie A, Bloemena E, Leemans CR, de B ee R. Sen- inel node biopsy o ea ly-s age o al ca i y cance : he VU Uni e si y Medical Cen e expe ience. Head Neck 2015;37:573–8. 44. Bell RB, Ma kiewicz MR, Die ks EJ, G e- goi e CE, Rade A. Thin se ial s ep sec ion- ing o sen inel lymph node biopsy specimen may no be necessa y o accu a ely s age he neck in o al squamous cell ca cinoma. J O al Maxillo ac Su g 2013;71:1268–77. 45. Dequan e D, Shahla M, Paulus P, Lo hai e P. Long e m esul s o sen inel lymph node biopsy in ea ly o al squamous cell ca cino- ma. Onco Ta ge s The 2013;6:799–802. 46. Rigual N, Lo ee T, F us ino J, Jayap akash V, Cohan D, Sulli an M, Ku iakose MA. Sen- inel node biopsy in lieu o neck dissec ion o s aging o al cance . JAMA O ola yngol Head Neck Su g 2013;139:779–82. 47. Cha u edi P, Da a S, A ya S, Ranga ajan V, Kane SV, Nai D, Nai S, Chauka DA, Pai PS, Pan aidya G, Deshmukh AD, Ag awal A, D’C uz AK. P ospec i e s udy o ul a- sound-guided ine-needle aspi a ion cy olo- gy and sen inel node biopsy in he s aging o clinically nega i e T1 and T2 o al cance . Head Neck 2015;37:1504–8. 48. B oglie MA, Hae le SK, Hube GF, Haile SR, S oeckli SJ. Occul me as ases de ec ed by sen inel node biopsy in pa ien s wi h ea ly o al and o opha yngeal squamous cell ca ci- nomas: impac on su i al. Head Neck 2013;35:660–6. 49. Melkane AE, Mamelle G, Wycisk G, Temam S, Jano F, Casi aghi O, Lumb oso J. Sen inel node biopsy in ea ly o al squamous cell ca cinomas: a 10-yea expe ience. La yngo- scope 2012;122:1782–8. 50. Yamauchi K, Fujioka Y, Kohno N. Sen inel node na iga ion su ge y e sus obse a ion as a managemen s a egy o ea ly ongue ca cinoma. Head Neck 2012;34:568–72. 51. B oglieMA, Haile SR, S oeckliSJ. Long- e m expe ience in sen inel node biopsy o ea ly o al and o opha yngeal squamous cell ca ci- noma. Ann Su g Oncol 2011;18:2732–8. 52. Chone CT, Ani eli MB, Magalha ˜es RS, F ei- as LL, Al emani A, Ramos CD, E chebehe e E, C espo AN. Impac o immunohis ochem- is y in sen inel lymph node biopsy in head and neck cance . Eu A ch O o hinola yngol 2013;270:313–7. 53. Ci an os FJ, Zi sch RP, Schulle DE, Ag a- wal A, Smi h RB, Nason R, Pe uzelli G, Gou in CG, Wong RJ, Fe is RL, El Nagga A, Ridge JA, Paniello RC, Owza K, McCall L, Chepeha DB, Ya b ough WG, Mye s JN. 1278 Mallo Maga in˜os e al. Sen inel lymph node biopsy accu a ely s ages he egional lymph nodes o T1–T2 o al squamous cell ca cinomas: esul s o a p ospec i e mul i-ins i u ional ial. J Clin Oncol 2010;28:1395–400. 54. Thomsen JB, Sø ensen JA, G upe P, K og- dahl A. Sen inel lymph node biopsy in o al cance : alida ion o echnique and clinical implica ions o added oblique plana lym- phoscin ig aphy and/o omog aphy. Ac a Radiol 2005;46:569–75. 55. Ionna F, Chiesa F, Longo F, Manola M, Villano S, Calab ese L, Las o ia S, Mozzillo N. P ognos ic alue o sen inel node in o al cance . Tumo i 2002;88:18. 56. S oeckli SJ, S eine H, P al z M, Schmid S. Is he e a ole o posi on emission omog- aphy wi h 18F- luo odeoxyglucose in he ini ial s aging o nodal nega i e o al and o opha yngeal squamous cell ca cinoma. Head Neck 2002;24:345–9. 57. Te ada A, Hasegawa Y, Ya abe Y, Hanai N, Ozawa T, Hi akawa H, Ma uo T, Kawaki a D, Mikami S, Suzuki A, Miyazaki T, Nakashima T. Follow-up a e in aope a i e sen inel node biopsy o N0 neck o al cance pa ien s. Eu A ch O o hinola yngol 2011;268:429–35. 58. Rigual N, Douglas W, Lamonica D, Wise- man S, Cheney R, Hicks J W, Lo ee T. Sen inel lymph node biopsy: a a ional ap- p oach o s aging T2N0 o al cance . La yn- goscope 2005;115:2217–20. 59. Heu eling DA, an Wee S, Ka agozoglu KH, de B ee R. E alua ion o he use o eehand SPECT o sen inel node biopsy in ea ly s age o al ca cinoma. O al Oncol 2015;51:287–90. 60. Thomsen JB, Sø ensen JA, G upe P, Ka s o J, K ogdahl A. S aging N0 o al cance : lymphoscin ig aphy and con en ional imag- ing. Ac a Radiol 2005;46:492–6. 61. C ame JD, S idha an S, Fe is RL, Du u i U, Saman S. Sen inel lymph node biopsy e sus elec i e neck dissec ion o s age I o II o al ca i y cance . La yngoscope 2019;129:162–9. 62. Vidal-Sica S, Vilal a Solsona A, Alonso Va gas MI. Sen inel node in melanoma and b eas cance . Cu en conside a ions.Re Esp Med Nucl Imagen Mol 2015;34:30–44. 63. Go e s TM, Sch eude WH, Klop WM, G u e s JP, Ro e s MM, Me kx MA, Takes RP. Quali y o li e a e di e en p ocedu es o egional con ol in o al cance pa ien s: c oss-sec ional su ey. Clin O ola yngol 2016;41:228–33. 64. Liu M, Wang SJ, Yang X, Peng H. Diagnos- ic e icacy o sen inel lymph node biopsy in ea ly o al squamous cell ca cinoma: a me a- analysis o 66 s udies. PLoS One 2017;12. e0170322. Add ess: Ma io Pe ´ ez Saya ´ns Ins i u o de In es igacio ´n Sani a ia de San iago (IDIS) En e ı ´os s/n San iago de Compos ela CP 15782 Spain Tel: +34 626233504. Fax: +34 986295424 E-mail: [email p o ec ed] Diagnos ic yield o SLNB in OSCC T1/T2-N0 1279