Correlation between koilocytes and human papillomavirus detection by PCR in oral and oropharynx squamous cell carcinoma biopsies

The purpose of this study was to compare the histopathological analysis with polymerase chain reaction (PCR) methods to predict the presence of human papillomavirus (HPV) infection in oral squamous cell carcinoma biopsies. Eighty-three paraffin-embedded tissue specimens from patients with oropharynx and mouth floor squamous cell carcinoma were submitted to histopathological analysis under light microscopy, specifically for the determination of the presence of koilocytes. Subsequently, DNA was purified from the same paraffin-embedded specimens and submitted to PCR. Fisher's exact test showed no statistically significant correlation between the two methods. The results suggest that the presence of koilocytes is unreliable for the detection of HPV presence in oral and oropharynx squamous cell carcinoma.

Squamous cell carcinoma in lichen planopilaris.

BACKGROUND Lichen planopilaris (LPP) is a rare variant of cutaneous lichen planus that preferentially involves hair follicles. OBSERVATION We describe the case of an 87-year-old woman with cicatricial alopecia due to lichen planopilaris. The diagnosis was based on clinical evaluation, histopathology and trichoscopy. Squamous cell carcinoma developed within the hairless area after 18 years of evolution. CONCLUSION It is necessary to consider the association between lichen planopilaris and squamous cell carcinoma and to ensure a close follow-up of LPP patients, especially when there is a long history of the disease or new a lesion develops, which does not correspond clinically or in trichoscopy to lichen planopilaris.

Prognostic value of arginase-II expression and regulatory T-cell infiltration in head and neck squamous cell carcinoma.

Tumor-infiltrating lymphocytes are present in a variety of tumors and play a central role in antitumor immune responses. Nevertheless, most cancers progress probably because tumors are only weakly immunogenic and develop multiple immunosuppressive mechanisms. In the present study, on head and neck squamous cell carcinoma, we found high intraepithelial infiltration of regulatory FOXP3(+) T cells, and relatively high levels of BDCA2(+) and FOXP3(+) cells in stromal (peripheral) regions of the tumors. Tumor-infiltrating (intraepithelial) FOXP3(+) T cells were significantly more frequent in patients with oropharynx and oral cavity squamous cell carcinoma and in patients without lymph node metastasis. Furthermore, arginase-II (ARG2) was expressed by 60%, inducible nitric oxide synthetase by 9%, cyclooxygenase-2 by 43%, and B-cell lymphoma 2 (BCL2) by 26% of tumors. Interestingly, the absence of ARG2 expression, enhanced stromal infiltration of CD11c(+) myeloid dendritic cells, and high numbers of FOXP3(+) T cells were each significantly associated with prolonged overall survival, and the latter two parameters were also confirmed by multivariate analysis. For disease-free survival, multivariate analysis revealed significant negative correlations with BCL2 and ARG2 expression by tumor cells. These findings shed new light on mechanisms of cancer progression, and provide rationales for therapeutic inhibition of immunosuppressive mechanisms in head and neck squamous cell carcinoma.

A positive FGFR3/FOXN1 feedback loop underlies benign skin keratosis versus squamous cell carcinoma formation in humans.

Seborrheic keratoses (SKs) are common, benign epithelial tumors of the skin that do not, or very rarely, progress into malignancy, for reasons that are not understood. We investigated this by gene expression profiling of human SKs and cutaneous squamous cell carcinomas (SCCs) and found that several genes previously connected with keratinocyte tumor development were similarly modulated in SKs and SCCs, whereas the expression of others differed by only a few fold. In contrast, the tyrosine kinase receptor FGF receptor-3 (FGFR3) and the transcription factor forkhead box N1 (FOXN1) were highly expressed in SKs, and close to undetectable in SCCs. We also showed that increased FGFR3 activity was sufficient to induce FOXN1 expression, counteract the inhibitory effect of EGFR signaling on FOXN1 expression and differentiation, and induce differentiation in a FOXN1-dependent manner. Knockdown of FOXN1 expression in primary human keratinocytes cooperated with oncogenic RAS in the induction of SCC-like tumors, whereas increased FOXN1 expression triggered the SCC cells to shift to a benign SK-like tumor phenotype, which included increased FGFR3 expression. Thus,we have uncovered a positive regulatory loop between FGFR3 and FOXN1 that underlies a benign versus malignant skin tumor phenotype.

Multifocalité du carcinome épidermoïde sur les voies digestive supérieure et respiratoire distale : technicité du diagnostic endoscopique [Multiple squamous cell carcinoma of the upper digestive and lower respiratory tracts : methodology of endoscopic screening]

L'étude porte sur 951 porteurs d'un cancer primaire bucco-pharyngo-laryngé, et révèle un taux de multifocalité du carcinome épidermoïde sur les voies digestive supérieure (bouche-pharynx-oesophage) et aérienne distale (larynx-trachée-bronches) s'élevant à 14,5 %. Les secondes localisations peuvent être simultanées (6,4 %) ou successives (8,1 %) à la découverte du premier cancer: dès la deuxième année du follow-up leur incidence dépasse celle des récidives. Elles se localisent tant au niveau ORL (8,5 %) qu'oesophagien (3 %) ou bronchique (3 %). Le cancer du voile présente un taux de multifocalité particulièrement élevé (51 %). Les auteurs décrivent un type d'endoscopie de dépistage (bucco-pharyngo-oesophago-laryngo-trachéobronchoscopie) dont la fiabilité repose sur une technicité spécifique d'une part, et sur la connaissance des caractéristiques propres aux secondes localisations d'autre part. Ce dépistage systématique permet de détecter les tumeurs secondaires à un stade le plus souvent précoce et encore asymptomatique.

A prospective study of salivary gland function in patients undergoing radiotherapy for squamous cell carcinoma of the oropharynx

Résumé: Le traitement du cancer avancé de la tête et du cou nécessite souvent une approche multidisciplinaire associant la chirurgie, la radiothérapie et la chimiothérapie. Chacun de ces traitements présente des avantages, des limites et des inconvénients. En raison de la localisation de la tumeur primaire et/ou des métastases ganglionnaires, les glandes salivaires majeures sont fréquemment touchées par les traitements oncologiques. La salive joue un rôle déterminant dans la cavité buccale car elle lubrifie les tissus et facilite à la fois la déglutition et l'élocution. Son contenu en électrolytes et en protéines, dont certaines possèdent un effet antibactérien, protège les dents de la déminéralisation par l'acidité. Une fonction normale, liée autant à la quantité qu'à la qualité de la salive, reste indispensable pour le maintien d'une bonne santé buccale. L'objectif de cette étude prospective a été de déterminer, dans un groupe homogène de patients, l'influence d'un traitement de radiothérapie sur divers paramètres salivaires comme la sécrétion, le pH et l'effet tampon, avant, pendant et jusqu'à un an après la fin du traitement. L'étude a aussi examiné le comportement de ces paramètres salivaires après une intervention chirurgicale seule au niveau de la tête et du cou, avec ou sans exérèse d'une glande sous- maxillaire. L'étude s'est basée sur 54 patients (45 hommes et 9 femmes) atteints d'un carcinome épidermoïde avancé avec une localisation oro-pharyngée confirmée (n = 50) ou soupçonnée (n = 4), adressés et investigués dans le Centre Hospitalier Universitaire Vaudois de Lausanne, Suisse. Tous ces patients furent traités par radiothérapie seule ou en combinaison avec une chirurgie et/ou une chimiothérapie. Trente-neuf des 54 patients parvinrent à la fin de cette étude qui s'est étendue jusqu'à 12 mois au-delà de la radiothérapie. La chirurgie de la tête et cou, en particulier après ablation de la glande sous-maxillaire, a révélé un effet négatif sur la sécrétion salivaire. Elle n'influence en revanche ni le pH, ni l'effet tampon de la salive. Cependant, l'effet sur la sécrétion salivaire lié à la chirurgie est progressivement masqué par l'effet de la radiothérapie et n'est plus identifiable après 3-6 mois. Dès le début de la radiothérapie, la sécrétion salivaire chût très manifestement pour diminuer progressivement jusqu'à 1/3 de sa capacité à la fin du traitement actinique. Une année après la fin de cette radiothérapie, la dysfonction salivaire est caractérisée par une diminution moyenne de la sécrétion salivaire, de 93 % (p < 0,0001) pour la salive au repos et de 95 % (p < 0.0001) pour la salive stimulée, par rapport aux valeurs pré-thérapeutiques. Le pH salivaire ainsi que l'effet tampon furent également influencés par le traitement actinique. L'effet tampon a présenté une diminution à 67 % à une année post-traitement en comparaison de sa valeur pré-thérapeutique. Le pH de la salive stimulée présente une légère, mais significative, diminution par rapport à sa valeur antérieure à la radiothérapie. En conclusion, la chirurgie des cancers de l'oropharynx précédant une radiothérapie a une influence négative sur la sécrétion salivaire sans aggraver l'hyposialie consécutive aux radiations ionisantes. Cette étude confirme qu'un traitement oncologique comprenant une irradiation totale des glandes salivaires majeures chez des patients atteints d'un carcinome épidermoïde avancé de la région oro-pharyngée, induit une perte sévère et à long terme de la sécrétion salivaire avec une altération du pH et de l'effet tampon Abstract: Objective. We sought to investigate the impact of head and neck cancer treatment on salivary function. Study design. The study was conducted on 54 patients with advanced squamous cell carcinoma with confirmed (n =50) or suspected (n = 4) primary oropharyngeal localization who were treated with radiation alone or in combination with surgery or chemotherapy, or both. The following groups were considered in the evaluation: 1, the entire pool of patients; 2, those undergoing surgery and those not undergoing surgery before radiation; 3, those undergoing resection and those not undergoing resection of the submandibular gland. The flow rates, pH, and buffering capacity were determined before, during, and up to 12 months after the completion of radiation. Results. Head and neck surgery, particularly when submandibular gland resection was performed, had a negative impact on salivary flow rates but did not influence pH or buffering capacity. Nonetheless, the effect of surgery on salivary flow rates decreased progressively and disappeared at 3 to 6 months after radiotherapy. More than two thirds of the salivary output was lost during radiation treatment. All patients were experiencing salivary dysfunction at 1 year after completion of radiotherapy, with average decreases of 93% (P < .0001) and 95% (P < .0001) for whole resting salivary flow and whole stimulated salivary flow, respectively, compared with the preradiotherapy values. The buffering capacity decreased to 67% of its preradiotherapy value, and whole stimulated saliva became acidic. Conclusions. The result of this study confirms that cancer treatment involving full-dose radiotherapy (RTH) to all major salivary glands for locally advanced squamous cell carcinoma of the oropharynx induces severe hyposalivation with alteration of salivary pH and buffering capacity. Head and neck surgery has a negative impact on salivary flow rates, especially when the submandibular gland is removed. However, surgery before irradiation is not a factor aggravating hyposalivation when postoperative radiotherapy includes all the major salivary glands.

Antibody-indocyanin conjugates for immunophotodetection of human squamous cell carcinoma in nude mice.

We have recently shown that immunophotodetection of human colon carcinomas in nude mice and in patients is possible by using anti-carcinoembryonic antigen monoclonal antibodies (MAb) coupled to fluorescein. The most common clinical application of photodiagnosis has been for the detection of squamous cell carcinomas (SCC) in the upper respiratory tract, but the free dyes used have a poor tumor selectivity. We selected the known MAb E48 directed against SCC and coupled it to a fluorescent dye: indopentamethinecyanin (indocyanin). This dye has an advantage over fluorescein in that it emits a more penetrating fluorescent red signal at 667 nm after excitation with a laser ray of 640 nm. In vitro, an conjugate with an indocyanin:MAb molar ratio of 2, and an additional trace labeling with 125I, showed more than 80% of binding to cells from the SCC line A431. In vivo, when injected i.v. into nude mice bearing xenografts of the same carcinoma line, the MAb E48-(indocyanin)2 conjugate was almost as efficient as the unconjugated MAb E48 in terms of specific tumor localization: 15% of the injected dose per g of tumor at 24 h after injection and a tumor:overall normal tissue ratio of 6-8. There was no selective tumor localization of an irrelevant IgG1-(indocyanin)2 conjugate. Immunophotodetection of the s.c. SCC xenografts on mice given injections of 100 micrograms of MAb E48-(indocyanin), conjugate (representing 1 microgram of indocyanin) was performed at 24 h. Upon laser irradiation, clearly detectable red fluorescence from the indocyanin-MAb conjugate was observed specifically in the SCC xenografts across the mouse skin. In comparison, injection of 100 micrograms of a MAb E48 coupled to 2 micrograms of fluorescein gave a specific green fluorescence signal in the tumor xenografts, which was detectable, however, only after removing the mouse skin. Injection i.v. of a 15 times higher amount of free indocyanin (15 micrograms) gave a diffuse red fluorescence signal all over the mouse body with no definite increase in intensity in the tumor, indicating a lack of tumor selectivity of the free dye. The results demonstrate the possibility of broadening and improving the efficiency of tumor immunophotodiagnosis by coupling to a MAb directed against SCC, a fluorescent dye absorbing and emitting at higher wavelength than fluorescein, and thus having deeper tissue penetration and lower tissue autofluorescence. Such a demonstration opens the way to a new form of clinical immunophotodiagnosis and possibly to the development of a more specific approach to phototherapy of early bronchial carcinomas.

Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial.

BACKGROUND: We aimed to compare panitumumab, a fully human monoclonal antibody against EGFR, plus radiotherapy with chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck. METHODS: In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 22 sites in eight countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (≥10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (two cycles of cisplatin 100 mg/m(2) during radiotherapy) or to radiotherapy plus panitumumab (three cycles of panitumumab 9 mg/kg every 3 weeks administered with radiotherapy) using a stratified randomisation with a block size of five. All patients received 70-72 Gy to gross tumour and 54 Gy to areas of subclinical disease with accelerated fractionation radiotherapy. The primary endpoint was local-regional control at 2 years, analysed in all randomly assigned patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This study is registered with ClinicalTrials.gov, number NCT00547157. FINDINGS: Between Nov 30, 2007, and Nov 16, 2009, 152 patients were enrolled, and 151 received treatment (61 in the chemoradiotherapy group and 90 in the radiotherapy plus panitumumab group). Local-regional control at 2 years was 61% (95% CI 47-72) in the chemoradiotherapy group and 51% (40-62) in the radiotherapy plus panitumumab group. The most frequent grade 3-4 adverse events were mucosal inflammation (25 [40%] of 62 patients in the chemoradiotherapy group vs 37 [42%] of 89 patients in the radiotherapy plus panitumumab group), dysphagia (20 [32%] vs 36 [40%]), and radiation skin injury (seven [11%] vs 21 [24%]). Serious adverse events were reported in 25 (40%) of 62 patients in the chemoradiotherapy group and in 30 (34%) of 89 patients in the radiotherapy plus panitumumab group. INTERPRETATION: Panitumumab cannot replace cisplatin in the combined treatment with radiotherapy for unresected stage III-IVb squamous-cell carcinoma of the head and neck, and the role of EGFR inhibition in locally advanced squamous-cell carcinoma of the head and neck needs to be reassessed. FUNDING: Amgen.

Radiothérapie externe accélérée postopératoire des carcinomes épidermoïdes localement évolués de la sphère ORL: étude prospective de phase II [Prospective study of accelerated postoperative radiation therapy in patients with squamous-cell carcinoma of the head and neck]

PURPOSE: To assess the feasibility and efficacy of accelerated postoperative radiation therapy (RT) in patients with squamous-cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Between December 1997 and July 2001, 68 patients (male to female ratio: 52/16; median age: 60-years (range: 43-81) with pT1-pT4 and/or pN0-pN3 SCCHN (24 oropharynx, 19 oral cavity, 13 hypopharynx, 5 larynx, 3 unknown primary, 2 maxillary sinus, and 2 salivary gland) were included in this prospective study. Postoperative RT was indicated because extracapsular infiltration (ECI) was observed in 20 (29%), positive surgical margins (PSM) in 20 (29%) or both in 23 patients (34%). Treatment consisted of external beam RT 66 Gy in 5 weeks and 3 days. Median follow-up was 15 months. RESULTS: According to CTC 2.0, acute morbidity was acceptable: grade 3 mucositis was observed in 15 (22%) patients, grade 3 dysphagia in 19 (28%) patients, grade 3 skin erythema in 21 (31%) patients with a median weight loss of 3.1 kg (range: 0-16). No grade 4 toxicity was observed. Median time to relapse was 13 months; we observed only three (4%) local and four (6%) regional relapses, whereas eight (12%) patients developed distant metastases without any evidence of locoregional recurrence. The 2 years overall-, disease-free survival, and actuarial locoregional control rates were 85, 73 and 83% respectively. CONCLUSION: The reduction of the overall treatment time using postoperative accelerated RT with weekly concomitant boost (six fractions per week) is feasible with local control rates comparable to that of published data. Acute RT-related morbidity is acceptable.

A phase 2 randomized trial of radiotherapy (RT) plus panitumumab compared to chemoradiotherapy in patients with unresected, locally advanced squamous cell carcinoma of the head and neck (SCCHN): interim pooled safety analysis

Background: Panitumumab (pmab), a fully human monoclonal antibody against the epidermal growth factor receptor (EGFR), is indicated as monotherapy for treatment of metastatic colorectal cancer. This ongoing study is designed to assess the efficacy and safety of pmab in combination with radiotherapy (PRT) compared to chemoradiotherapy (CRT) as initial treatment of unresected, locally advanced SCCHN (ClinicalTrials.gov Identifier: NCT00547157). Methods: This is a phase 2, open-label, randomized, multicenter study. Eligible patients (pts) were randomized 2:3 to receive cisplatin 100 mg/m2 on days 1 and 22 of RT or pmab 9.0 mg/kg on days 1, 22, and 43. Accelerated RT (70 to 72 Gy − delivered over 6 to 6.5 weeks) was planned for all pts and was delivered either by intensity-modulated radiation therapy (IMRT) modality or by three-dimensional conformal (3D-CRT) modality. The primary endpoint is local-regional control (LRC) rate at 2 years. Key secondary endpoints include PFS, OS, and safety. An external, independent data monitoring committee conducts planned safety and efficacy reviews during the course of the trial. Results: Pooled data from this planned interim safety analysis includes the first 52 of the 150 planned pts; 44 (84.6%) are male; median (range) age is 57 (33−77) years; ECOG PS 0: 65%, PS 1: 35%; 20 (39%) pts received IMRT, and 32 (61%) pts received 3D-CRT. Fifty (96%) pts completed RT, and 50 pts received RT per protocol without a major deviation. The median (range) total RT dose administered was 72 (64−74) Gy. The most common grade _ 3 adverse events graded using the CTCAE version 3.0 are shown (Table). Conclusions: After the interim safety analysis, CONCERT-2 continues per protocol. Study enrollment is estimated to be completed by October 2009.

Pattern and clinical significance of cancer-testis gene expression in head and neck squamous cell carcinoma

Les cancer-testis antigènes appartiennent à la famille des antigènes tumoraux spécifiques. Ils ont montré un pouvoir immunogène chez les patients porteurs de différents cancers. En effet, ils stimulent sélectivement les lymphocytes cytotoxiques, et leur expression spécifique dans les tissus tumoraux en fait une cible idéale pour une vaccination antitumorale. Le but de cette étude est d'identifier l'expression de certains de ces antigènes, d'analyser leur valeur pronostique et de déterminer la meilleure cible antigénique pour permettre une immunothérapie spécifique dans les carcinomes épidermoïdes des voies aérodigestives supérieures. Le profil et le taux d'expression de 12 cancer-testis antigènes (MAGE-A1, MAGE-A3, MAGE-A4, MAGEA10, MAGE-C2, NY-ESO-1, LAGE-1, SSX-2, SSX-4, BAGE, GAGE-1/2, GAGE-3/4) et de 3 autres antigènes tumoraux spécifiques (PRAME, HERV-K-MEL, NA-17A) ont été évalués par RT-PCR sur 57 échantillons de cancers ORL primaires. Les paramètres tumoraux et cliniques ont été prospectivement collectés afin de corréler ces données avec le résultat de nos investigations immunobiologiques. Quatre-vingt-huit pour cent des tumeurs expriment au moins 1 antigène. Une co-expression de 3 gènes ou plus est détectée chez 59% des patients. MAGE-A4 (60%), MAGE-A3 (51%), PRAME (49%) et HERV-K-MEL (42%) sont les gènes le plus fréquemment exprimés. Ils sont totalement absents des muqueuses saines avoisinantes. La présence de MAGE-A et NY-ESO-1 à la surface des cellules a été vérifiée par immunohistochimie. Nos analyses statistiques ont permis d'identifier une diminution de la survie liée au cancer chez les patients porteurs d'une tumeur exprimant de multiples cancer-testis antigènes et notamment MAGE-A4 dont l'expression indépendante d'autres éléments cliniques s'associe statistiquement à un taux de survie diminué. Nos résultats ont permis d'identifier un rôle pronostique de l'expression des gènes associés aux tumeurs dont l'expression est apparemment liée à un phénotype de malignité plus élevé. Cette constatation, corroborée par l'identification parallèle d'un infiltrat lymphocytaire spécifique confirme l'utilité potentielle de certains cancer-testis antigènes comme cible pour une immunothérapie ciblée dans les carcinomes des voies aérodigestives supérieures

Squamous cell carcinoma of the larynx with subglottic extension: is larynx preservation possible?. Plattenepithelkarzinom des Larynx mit subglottischer Ausdehnung: ist ein Larynxerhalt möglich ?

PURPOSE: Squamous cell carcinoma of larynx with subglottic extension (sSCC) is a rare location described to carry a poor prognosis. The aim of this study was to analyze outcomes and feasibility of larynx preservation in sSCC patients. PATIENTS AND METHODS: Between 1996 and 2012, 197 patients with sSCC were treated at our institution and included in the analysis. Stage III-IV tumors accounted for 76 %. Patients received surgery (62 %), radiotherapy (RT) (18 %), or induction chemotherapy (CT) (20 %) as front-line therapy. RESULTS: The 5-year actuarial overall survival (OS), locoregional control (LRC), and distant control rate were 59 % (95 % CI 51-68), 83 % (95 % CI 77-89), and 88 % (95 % CI 83-93), respectively, with a median follow-up of 54.4 months. There was no difference in OS and LRC according to front-line treatments or between primary subglottic cancer and glottosupraglottic cancers with subglottic extension. In the multivariate analysis, age > 60 years and positive N stage were the only predictors for OS (HR 2, 95 % CI 1.2-3.6; HR1.9, 95 % CI 1-3.5, respectively). A lower LRC was observed for T3 patients receiving a larynx preservation protocol as compared with those receiving a front-line surgery (HR 14.1, 95 % CI 2.5-136.7; p = 0.02); however, no difference of ultimate LRC was observed according to the first therapy when including T3 patients who underwent salvage laryngectomy (p = 0.6). In patients receiving a larynx preservation protocol, the 5-year larynx-preservation rate was 55 % (95 % CI 43-68), with 36 % in T3 patients. The 5-year larynx preservation rate was 81 % (95 % CI 65-96) and 35 % (95 % CI 20-51) for patients who received RT or induction CT as a front-line treatment, respectively. CONCLUSION: Outcomes of sSCC are comparable with other laryngeal cancers when managed with modern therapeutic options. Larynx-preservation protocols could be a suitable option in T1-T2 (RT or chemo-RT) and selected T3 sSCC patients (induction CT).

Correlation between subjective evaluation of symptoms and objective findings in early recurrent head and neck squamous cell carcinoma.

IMPORTANCE: This study addresses the value of patients' reported symptoms as markers of tumor recurrence after definitive therapy for head and neck squamous cell carcinoma. OBJECTIVE: To evaluate the correlation between patients' symptoms and objective findings in the diagnosis of local and/or regional recurrences of head and neck squamous cell carcinomas in the first 2 years of follow-up. DESIGN: Retrospective single-institution study of a prospectively collected database. SETTING: Regional hospital. PARTICIPANTS: We reviewed the clinical records of patients treated for oral cavity, oropharyngeal, laryngeal, and hypopharyngeal carcinomas between January 1, 2008, and December 31, 2009, with a minimum follow-up of 2 years. MAIN OUTCOMES AND MEASURES: Correlation between symptoms and oncologic status (recurrence vs remission) in the posttreatment period. RESULTS: Of the 101 patients included, 30 had recurrences. Pain, odynophagia, and dysphonia were independently correlated with recurrence (odds ratios, 16.07, 11.20, and 5.90, respectively; P < .001). New-onset symptoms had the best correlation with recurrences. Correlation was better between 6 to 12 and 18 to 21 months after therapy and in patients initially treated unimodally (P < .05). Primary stage and tumor site had no effect. CONCLUSIONS AND RELEVANCE: The correlation between symptoms and oncologic status is low during substantial periods within the first 2 years of follow-up. New-onset symptoms, especially pain, odynophagia, or dysphonia, better correlate with tumor recurrence, especially in patients treated unimodally.