Verrucous esophageal carcinoma is a unique indolent subtype of squamous cell carcinoma: a systematic review and individual patient regression analysis.

BACKGROUND AND AIMS: Verrucous esophageal carcinoma (VEC) is a rare malignancy that presents a diagnostic challenge. We aim to characterize the clinical and genomic features, tumor behavior, and treatment outcomes of VEC to guide clinical practice. METHODS: We performed a systematic review of the literature and identified additional cases from Massachusetts General Hospital records and The Cancer Genome Atlas (TCGA). We obtained individual VEC patient data and analyzed publicly available clinicogenomic data from TCGA. We performed a regression analysis comparing cases of VEC to esophageal squamous cell carcinoma (ESCC) to identify factors influencing survival. RESULTS: A total of 135 patients were reported in 82 publications, and four unpublished cases from Massachusetts General Hospital (median age 65 years, 69% males, 48% smokers, 33% consumed alcohol). Symptoms were present at diagnosis in 95% of patients, most commonly dysphagia and weight loss. Median symptom onset to diagnosis time was 11.5 months with frequent misdiagnosis as Candida esophagitis. Among VEC cases with pathologic staging, lymph node metastases were rare (5%) compared to ESCC (40%). VEC was genomically characterized by enrichment of SMARCA4 missense mutations and a lack of pathogenic TP53 mutations. Despite its diagnostic elusiveness, in a multivariate regression analysis, VEC was detected at earlier stages (p = < 0.001) compared to ESCC, and advanced stage was the only significant factor affecting survival (p = 0.013). CONCLUSIONS: VEC is a rare, clinically and genomically distinct subtype of ESCC. Recognition and diagnosis of this lesion may allow the pursuit of curative and less morbid treatment strategies.

Clinicopathologic analysis of verrucous hyperplasia, verrucous carcinoma and squamous cell carcinoma as part of the clinicopathologic spectrum of oral proliferative verrucous leukoplakia: A literature review and analysis.

OBJECTIVE: Proliferative verrucous leukoplakia is classified as a potentially malignant disorder because of its high rate of malignant transformation. PVL progresses in a series of clinical stages where the early stage represents multiple, multifocal leukoplakias with a high recurrence rate. The intermediate and late stages are clinically exophytic lesion, diagnosed microscopically as verrucous hyperplasia that often progresses into verrucous carcinoma and/or squamous cell carcinoma. There is no single histologic definition and the diagnosis is retrospective following observed progression of the disorder. The goal of the current study was to conduct a literature review and analysis of PVL in the later stages to gain further knowledge on their clinicopathologic features. DATA SOURCES: Medline's PubMed and Google Scholar were searched for adequately documented cases from 1985 to 2018. References of published articles were searched for additional cases. REVIEW METHODS: Overall, 57 manuscripts were analyzed. 35/57 manuscripts provided adequate data on the clinicopathologic features in the premalignant and malignant stages. RESULTS: Malignant transformation rate was 50% (average of 57 months). Gingiva, palate and buccal mucosa were the most common locations. Clinicopathologic features included; well differentiated carcinoma (78%), perineural invasion (3%), lymph node metastasis (4%); distant metastasis (0%), average duration of illness (65 months), DOD-dead of disease (44%). Moderate dysplasia, severe dysplasia and carcinoma in situ were exceptionally uncommon in the premalignant stages (0.8%). CONCLUSION: Prognostic factors such as perineural invasion, lymph node metastasis and distant metastasis were uncommon occurrences which may have practical implications on treatment. Further studies are needed to substantiate our findings.

A population-based analysis of verrucous carcinoma of the oral cavity.

OBJECTIVES: To describe the incidence and determinants of survival of patients with verrucous carcinoma (VC) of the oral cavity between the years of 1973 and 2012 using the Surveillance, Epidemiology, and End Results (SEER) database. STUDY DESIGN: Retrospective cohort study using a national database. METHODS: The SEER registry was utilized to calculate survival trends for patients with VC of the oral cavity between 1973 and 2012. Patient data was then analyzed with respect to histopathology, age, sex, race, stage, grade, and treatment modalities (surgery and radiation therapy). Overall survival (OS) and disease-specific survival (DSS) were calculated. RESULTS: A total of 1,481 cases of VC of the oral cavity were identified. The cohort was composed of 50.5% males. The mean age at diagnosis was 69.5 years. The oral tongue was the most common primary site (28.9%), followed by the alveolar ridge (21.4%) and buccal mucosa (19.0%). The vast majority of cases (79.1%) presented with stage I and stage II disease. Nodal disease was present in only 1.6% of cases. The median OS was 94.6 months. Eighty-seven percent of cases underwent surgery, and 11.5% received both surgery and radiation therapy. Overall survival at 2, 5, and 10 years was 83%, 64%, and 42%, respectively. On multivariate analysis, advanced age (P < 0.001) and stage (P < 0.001) were associated with worse OS, whereas surgery improved OS (P = 0.047). CONCLUSION: We provide the first population-based analysis of prognostic factors affecting survival outcomes in patients with oral cavity VC. Verrucous carcinoma of the oral cavity is associated with a generally favorable prognosis. Age, stage, nodal status, and surgical therapy are independent predictors of OS. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:393-397, 2018.

Adjuvant radiotherapy is not supported in patients with verrucous carcinoma of the oral cavity.

OBJECTIVE: To analyze the impact of adjuvant radiation therapy (RT) on overall survival (OS) and disease-specific survival (DSS) in patients with verrucous carcinoma (VC) as compared to squamous cell carcinoma (SCC) of the oral cavity. STUDY DESIGN: Cross-sectional population analysis. METHODS: Cases of nonmetastatic VC/SCC of the oral cavity were extracted from the Surveillance, Epidemiology, and End Results (SEER) database (1988-2013). Kaplan-Meier survivals, stratified according to T stage, were compared between VC and SCC for treatment with or without adjuvant RT. RESULTS: A total of 18,819 VC/SCC cases were identified. There were 581 (3.1%) VC (mean age 69.6 years, 48.9% female) versus 18,238 (97.0%) SCC (mean age, 65.3, 37.1% female) patients. Verrucous carcinoma patients receiving surgery alone (N = 539) demonstrated a trend toward improved OS versus VC patients receiving surgery and RT (N = 40) (117.0 vs. 71.4 months, respectively, P = 0.119). There was a statistically significant improvement in DSS in VC patients receiving surgery alone (217.2 vs. 110.9 months, P = 0.05). Verrucous carcinoma patients treated with adjuvant RT demonstrated a trend toward a worse OS (71.4 vs. 93.0 months, P = 0.992) and DSS (110.9 vs. 162.3 months, P = 0.275) compared to SCC treated with adjuvant RT, suggesting a different biology and radiosensitivity between VC and SCC. CONCLUSION: Verrucous carcinoma treated with adjuvant RT had a worse OS and DSS compared to both VC treated with surgery alone and SCC treated with surgery and adjuvant RT. Consideration should be given to surgical re-section rather than adjuvant RT in patients with positive margins or local recurrence. LEVEL OF EVIDENCE: 2C. Laryngoscope, 127:1334-1338, 2017.

Laryngeal Verrucous Carcinoma.

Objective Laryngeal verrucous carcinoma (LVC) is a rare, locally invasive neoplasm comprising 1% to 3.4% of laryngeal carcinomas. Management strategies are a topic of ongoing conversation, and no definitive treatment protocol based on T stage and presentation exists. This review examines characteristics, treatment modalities, and patient outcomes of LVC. Data Sources PubMed, MEDLINE, EMBASE, and Web of Science. Methods Databases were searched through October 29, 2015, for literature detailing individual patient cases of LVC. Variables analyzed included patient demographics, tumor characteristics, tumor size, treatment, and outcomes. Results Thirty-seven articles with 369 cases were included. LVC was found more commonly in males (13.8:1), at an average age of 58.7 years, and located in the glottis (74.0%). Most patients had local disease at presentation (94.9%). The most common presenting symptom was hoarseness (92.3%). The most common primary treatment was surgery alone (72.3%), with local excision as the most common technique (56.8%). In patients with data available on both surgical modality and T stage, most patients who presented as T1 and were managed surgically underwent local excision (79.2%). Surgical treatment alone led to high rates of disease-free survival at follow-up (86.8%). A large number of patients presenting with T1 disease were disease free at follow-up (88.6%). Overall survival was 80.3%. Conclusion LVC is most often managed surgically. The extent of surgical resection may be guided by T stage, with smaller tumors resected via local excision and larger tumors via partial or total laryngectomy. Regardless of T stage or therapy, LVC has a good posttreatment prognosis.

Susceptibility to oral cancers with CD95 and CD95L promoter SNPs may vary with the site and gender.

We investigated risk association of oral cancers (tongue and buccal mucosa cancers) with FAS (-1377G > A and FAS -670 A > G) and FASL (-844 T > C) SNPs, in males and females. A case-control study of 535 oral cancer and 525 control subjects was performed. SNPs were detected in the genomic DNA isolated from peripheral blood using PCR-RFLP. We report FASL -844 T > C SNPs increased risk for buccal mucosa cancer in females but not in males. On the other hand, FAS genotypes did not alter the risk of the cancers in both females and males. However, co-occurrence of FAS -1377 GA and -670 GG, FAS -1377 AA and -670 GG genotypes, and combined genotypes of FAS and FASL (FAS -1377 AA + FAS -670 GG + FASL -844 CC) alter male susceptibility towards tongue cancer. In females, combined genotypes of FAS (-1377GA and -670 AA) were found to be a risk factor of buccal mucosa cancer (OR = 3.27, CI = 1.28-8.36; P ≤ 0.01). FASL variants (GA and AA) increased tongue cancer risk in females who were tobacco users compared to non-tobacco users. In conclusion, SNPs of the FAS and FASL might alter risk of tongue and buccal mucosa cancers differentially, in a gender-dependent manner.

Exclusive radiotherapy for stage T1-T2N0M0 lanryngeal cancer: retrospective study of 59 patients at CFB and CHU de Caen.

OBJECTIVE: Study of patients with stage T1N0M0 or T2N0M0 glottic cancer treated by exclusive radiotherapy and comparison of the survival and functional results of this series with those of the literature. METHOD: Retrospective study of stage T1N0M0 or T2N0M0 glottic cancers diagnosed between 1st January 2000 and 31st December 2010 and treated by exclusive radiotherapy. Evaluation of survival, recurrence and larynx preservation rates. STUDY CENTRES: CLCC François-Baclesse and CHU de Caen. PATIENTS: Fifty-nine patients (53 men and sixwomen) treated for glottic cancer (57 squamous cell carcinomas, two verrucous carcinomas) comprising 51 T1N0M0 and eight T2N0M0 tumours. Treatment with exclusive radiotherapy (mean dose of 70 Grays limited to the thyroid cartilage for 57 patients, with lymph node irradiation for two patients). RESULTS: In this series, five (9.8%) patients with stage T1N0M0 glottic cancer and three patients (37.5%) with stage T2N0M0 glottic cancer relapsed, corresponding to a global recurrence rate of 13.6%. Three of the eight recurrences involved lymph nodes exclusively (N), two patients relapsed exclusively at the primary tumour site (T) and three patients presented local and lymph node recurrence (T and N). Treatment consisted of salvage total laryngectomy with bilateral cervical lymph node dissection in three cases, bilateral cervical lymph node dissection and sensitized radiotherapy in two cases, exclusive chemotherapy in one case, cervical lymph node dissection and cervical radiotherapy in one case. The last patient with recurrence died prior to salvage therapy. The larynx preservation rate was 94.9%. CONCLUSION: In comparison with the literature, treatment of stage T1-T2N0M0 glottic cancer by exclusive radiotherapy gives very good results, with a larynx preservation rate of 95%.

The prognostic importance of midline involvement in oral tongue cancer.

OBJECTIVES: To examine the importance of midline involvement and other clinicopathologic factors in predicting the rate of contralateral lymph node metastasis and survival in oral tongue squamous cell carcinoma. METHODS: We used Surveillance, Epidemiology, and End Results data to identify a cohort of 5430 patients with laterally rising tumors. Clinicopathologic factors examined as potentially predictive of contralateral lymph node metastasis included extension to midline, T classification, anatomic site, grade, histologic subtype, race, age, and sex. Survival analysis included the above factors plus lymph node status. RESULTS: T1 tumors and lateral T2 and T3 tumors had rates of contralateral lymph node metastasis ranging from 0.7% to 0.9% on presentation. T4 lesions and midline crossing T2 and T3 lesions had corresponding rates of 8.3% to 13.0%. Primary extension across the midline was associated with a mean survival about half that of strictly lateral tumors and its significance was maintained in multivariate analysis. CONCLUSIONS: Patients with T1 disease or T2-3 disease that does not cross midline are in a different prognostic class from patients with T2-3 disease that crosses midline or T4 tumors. These results give the strongest evidence to date that involvement of the midline is a powerful predictor for decreased survival in oral tongue squamous cell carcinoma.

Surgical outcome in patients with oral verrucous carcinoma: long-term follow-up in an endemic betel quid chewing area.

BACKGROUND/AIMS: To evaluate the clinical features and prognosis of patients with oral verrucous carcinoma (OVC) in an endemic betel quid chewing area. METHODS: A retrospective review was conducted in 39 patients with OVC treated surgically from 1991 to 2002. RESULTS: Thirty-seven patients (94.9%) were male. The median age at diagnosis was 53.8 years. All patients had been exposed to betel quid, cigarette smoking, and/or alcohol. The most common site of tumor origin was the buccal mucosa (64.1%). The tumor control rate was 97.4% after the first surgical procedure. Second/multiple primary tumors (SPTs/MPTs) were found in 21 patients. There were 13 deaths during the follow-up period, with SPTs/MPTs being the most common cause. The cancer-specific survival rate was 89.1% at 5 years, but continued to decrease thereafter. CONCLUSION: Surgery was effective for controlling OVC. However, long-term follow-up was necessary because of the high incidence of SPTs/MPTs and its impact on patient survival.

Truths and myths about radiotherapy for verrucous carcinoma of larynx.

PURPOSE: The role of primary radiotherapy (RT) for laryngeal verrucous carcinoma (LVC) is controversial because of concerns about anaplastic transformation, an increased incidence of metastases, and poorer local control after RT. To address these concerns, we report our experience. METHODS AND MATERIALS: All patients with pathologically diagnosed LVC treated with primary RT at our institution between 1961 and 2004 were reviewed. The local control, overall survival, and disease-specific survival rate were established. The outcome after salvage treatment and the incidence of metastases and anaplastic transformation were determined. RESULTS: Of 62 LVC patients with a minimal follow-up of 2 years, 20 local and 1 nodal recurrence were identified. Salvage surgery was undertaken in 18 of the 21 patients, and disease control was achieved in 17; the eighteenth patient died of a complication after surgery. Ultimate laryngeal preservation was achieved in 50 patients (81%), including 42 after initial RT and an additional 8 after salvage surgery. Distant failure and anaplastic transformation were not observed. Second cancers after RT were identified in 4 patients, only 1 of which was a head-and-neck cancer detected 11 years later. Of the 39 deceased patients, only 3 died of LVC. The local control, overall survival, and disease-specific survival rate at 5 years was 66% (95% confidence interval, 52-77%), 87% (95% confidence interval, 75-93%), and 97% (95% confidence interval, 87-99%), respectively. CONCLUSION: The results of our study have shown that the initial control of LVC with RT is less reliable compared with reports from surgical series; however, local recurrence was almost always salvaged successfully, resulting in disease-specific survival rates equivalent to those of surgical series. Neither anaplastic transformation nor unusual metastasis development was observed in this series.

Radioterapia y el carcinoma verrucoso de laringe: [revisión] / Radiotherapy and verrucous carcinoma of the larynx: [revision]

El carcinoma más común en las vías aéreo-digestivas superiores (VADS) es el carcinoma de células escamosas (>90%). Es difícil precisar la prevalencia de las denominadas variantes del carcinoma de células escamosas (CCE). El diagnóstico diferencial es necesario dadas sus diferencias no sólo en el manejo sino también en su pronóstico. El carcinoma verrucoso es una de las variantes del carcinoma de células escamosas bien diferenciado no metastizante, caracterizado por ser una neoplasia de un crecimiento lento, de patrón exofítico verrucoso. El rol de la radioterapia (RDT) en el tratamiento del carcinoma verrucoso es motivo de discusión por su posible transformación en carcinoma anaplásico. A través de la siguiente revisión bibliográfica se busca aclarar dicha controversia.

Squamous cell carcinoma is the most common upper aerodigestive tract (UAT) carcinoma (>90%). Precising the prevalence of the so-called varieties of squamous cell carcinoma has proved difficult. Differential diagnosis is necessary, on account of the differences between varieties both in management and prognosis. One of such varieties, verrucous carcinoma of the larynx, is a well-defined, no-metastatic tumor, characterized as a slow-growth neoplasm, of verrucous exophyitic pattern. Since laryngeal verrucous cancer may transform into anaplastic carcinoma, the role of radiotherapy in its treatment has been discussed. The aim of the present literature review was to shed light on this controversy.

Verrucous oral carcinoma: clinical findings and treatment outcomes in 74 patients in Northwest Italy.

AIM: Oral squamous cell carcinoma (OSCC) is an extremely invasive tumour of stratified squamous epithelium that spreads throughout degradation of the basement membrane (BM) and extracellular matrix (ECM). Oral verrucous carcinoma (VC) is a rare low-grade variant of OSCC. VC has a different clinical behaviour from classical OSCC and the optimal treatment is controversial. This report analyses the clinical features and outcomes in patients undergoing treatment for oral VC. METHODS: A group of 74 Northern Italian patients were studied; for each patient, agreement of histological diagnosis, age and gender, risk factors, tumor site, T classification, treatment, outcome and survival rate were examined and analysed statistically. RESULTS: The survival rate was 93.65% at 5 years and 83.44% at 10 years. Retrospective analysis showed no risk of cervical lymph node metastasis and surgical treatment results were good. CONCLUSION: Our survival rates showed a good prognosis, with no risk of cervical lymph node metastases, suggesting that most cases can be controlled by surgery alone.

Human papillomavirus and penile cancers in Rio de Janeiro, Brazil: HPV typing and clinical features.

OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) DNA in penile cancers in Rio de Janeiro, Brazil. MATERIALS AND METHODS: We studied, prospectively, 80 consecutive cases of patients with penile cancers who underwent surgical treatment at three different Hospitals in Rio de Janeiro between March 1995 and June 2000. Of these patients, 72 were diagnosed with invasive squamous cell carcinoma and 8 patients with verrucous carcinoma. The following parameters were observed: presence or absence of HPV DNA viral type, histological subtypes, clinical stage and overall survival. RESULTS: HPV DNA was detected in 75% of patients with invasive carcinomas and in 50% of patients with verrucous carcinomas. High risk HPVs were detected in 15 of 54 (27.8%) patients with HPV positive invasive tumors and in 1 of 4 (25%) patients with HPV positive verrucous tumors. HPV 16 was the most frequent type observed. No correlation was observed between HPV status and histological subtype (p = 0.51) as well as HPV status and stage stratification (p = 0.88). HPV status was also not significantly associated with the presence of regional metastases (p = 0.89). The overall survival was related to the presence of lymph node metastases (p < 0.0001). CONCLUSIONS: HPV infection may have contributed to malignant transformation in a large proportion of our penile cancer cases but only inguinal metastasis was a prognostic factor for survival in these patients with penile carcinoma.

Human papillomavirus and penile cancers in Rio de Janeiro, Brazil: HPV typing and clinical features

OBJECTIVE: To determine the prevalence of human papillomavirus (HPV) DNA in penile cancers in Rio de Janeiro, Brazil. MATERIALS AND METHODS: We studied, prospectively, 80 consecutive cases of patients with penile cancers who underwent surgical treatment at three different Hospitals in Rio de Janeiro between March 1995 and June 2000. Of these patients, 72 were diagnosed with invasive squamous cell carcinoma and 8 patients with verrucous carcinoma. The following parameters were observed: presence or absence of HPV DNA viral type, histological subtypes, clinical stage and overall survival. RESULTS: HPV DNA was detected in 75 percent of patients with invasive carcinomas and in 50 percent of patients with verrucous carcinomas. High risk HPVs were detected in 15 of 54 (27.8 percent) patients with HPV positive invasive tumors and in 1 of 4 (25 percent) patients with HPV positive verrucous tumors. HPV 16 was the most frequent type observed. No correlation was observed between HPV status and histological subtype (p = 0.51) as well as HPV status and stage stratification (p = 0.88). HPV status was also not significantly associated with the presence of regional metastases (p = 0.89). The overall survival was related to the presence of lymph node metastases (p < 0.0001). CONCLUSIONS: HPV infection may have contributed to malignant transformation in a large proportion of our penile cancer cases but only inguinal metastasis was a prognostic factor for survival in these patients with penile carcinoma.

Mohs micrographic surgery for penile cancer: management and long-term followup.

PURPOSE: Mohs micrographic surgery is efficacious for the primary treatment and local recurrence control of nongenital and cutaneous squamous and basal cell cancers. The efficacy of this procedure for squamous cell carcinoma of the penis was reviewed. MATERIALS AND METHODS: We retrospectively reviewed the charts of all patients treated with Mohs micrographic surgery for penile cancer at our institution from 1988 to 2006. RESULTS: We identified 33 patients who underwent a total of 41 Mohs procedures. Average +/- SD lesion size was 509 +/- 699 mm(2). An average of 2.6 +/- 1.4 stages were done using Mohs micrographic surgery. Five procedures were terminated with positive margins, including 3 due to urethral involvement and 2 due to defect size. Of the tumors 26 were stage Tis, 4 were T1, 7 were T2 and 4 were T3. A total of 13 defects were reconstructed by primary repair or granulation, 4 were reconstructed by skin grafts and 25 were reconstructed by tissue flaps and urethroplasty. Followup data were available on 25 patients at a mean of 58 +/- 63 months. Eight patients (32%) had recurrence, which was managed by repeat Mohs micrographic surgery in 7 and by penectomy in 1. There were 2 cases of tumor progression, including 1 from T1 to T3 disease (meatal involvement) and 1 from T1 to inguinal lymph node involvement. Two patients died, of whom 1 had no evidence of penile cancer and 1 had metastatic disease. CONCLUSIONS: Mohs micrographic surgery for low stage penile cancer results in a relatively high local recurrence rate. However, with repeat procedures and vigilant followup cancer specific and overall survival rates are excellent and progression rates are low.

Prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan.

BACKGROUND: In Taiwan, a distinct ethnic group variation in incidence and mortality rates has been suggested for most carcinomas. Our aim is to identify the role of prognostic factors associated with the survival of oral and pharyngeal carcinoma in Taiwan. METHODS: Taiwan Cancer Registry records of 9039 subjects diagnosed with oral and pharyngeal carcinoma were analyzed. The population was divided into three ethnic groups by residence, which were Taiwanese aborigines, Hakka and Hokkien communities. Five-year survival rates were estimated by Kaplan-Meier methods. Ethnic curves differed significantly by log-rank test; therefore separate models for Taiwanese aborigines, Hakka and Hokkien were carried out. The Cox multivariate proportional hazards model was used to examine the role of prognostic factors on ethnic survival. RESULTS: The five-year survival rates of oral and pharyngeal carcinoma were significantly poorer for Hokkien community (53.9%) and Taiwanese aborigines community (58.1%) compared with Hakka community (60.5%). The adjusted hazard ratio of Taiwanese aborigines versus Hakka was 1.07 (95%CI, 0.86-1.33) for oral and pharyngeal carcinoma mortality, and 1.16 (95%CI, 1.01-1.33) for Hokkien versus Hakka. Males had significantly poor prognosis than females. Subjects with tongue and/or mouth carcinoma presented the worst prognosis, whereas lip carcinoma had the best prognosis. Subjects with verrucous carcinoma had better survival than squamous cell carcinoma. Prognosis was the worst in elderly subjects, and subjects who underwent surgery had the highest survival rate. CONCLUSION: Our study presented that predictive variables in oral and pharyngeal carcinoma survival have been: ethnic groups, period of diagnosis, gender, diagnostic age, anatomic site, morphologic type, and therapy.

CO(2) laser surgery in the treatment of glottic cancer.

BACKGROUND: The aim of the study was to assess the effectiveness of CO(2) laser endoscopic surgery in the treatment of glottic carcinoma limited to the true vocal cords or involving the adjacent regions. METHODS: Seven hundred nineteen patients (687 men and 32 women; mean age, 60.4 years; range, 33-86 years) with glottic carcinoma (432 T1N0M0, 236 T2N0M0, 51 T3N0M0) underwent CO(2) laser surgery (mean follow-up, 5 years; range, 2-17 years). Statistical comparison was carried out with Wilcoxon test, considering p < .05 the minimum significance value. RESULTS: Overall actuarial survival, adjusted actuarial survival, and percentage of patients with no evidence of disease at 5 years were 85%, 97%, and 85%, respectively, in patients with T1a disease; 84%, 96%, and 83% in those with T1b disease; 77%, 86%, and 61% in those with T2 unilateral tumors; 77%, 88%, and 55% in those with T2 bilateral tumors; and 64%, 72%, and 60% in those with T3 disease. The statistical analysis showed the following: significant differences in the comparison of T1 versus T2 and T2 versus T3 tumors (p < .01), with the exception of no evidence of disease in the comparison of T2 versus T3 (p > .05); and no significant differences in the comparison of unilateral and bilateral tumors (p > .05). Actuarial local control, actuarial nodal control, and actuarial distant metastasis control at 5 years were 85%, 98%, and 99%, respectively, in patients with T1 disease; and 66%, 82%, and 91% in patients with T2 disease; and 66%, 83%, and 95% in patients with T3 disease. The laryngeal preservation rate was 97.3% in the T1 group, 82.5% in the T2 group, and 80.5% in T3 group. CONCLUSIONS: CO(2) laser endoscopic surgery is effective in the treatment of glottic carcinoma not infiltrating the cartilaginous skeleton; the results achieved are competitive with those of open conservative operations, if we take into account the possibilities afforded by salvage surgery and the rate of laryngeal preservation achieved in the study patients.

Verrucous carcinoma of the skin: long-term follow-up results following surgical therapy.

BACKGROUND: Owing to the benign appearance and slow growth of verrucous carcinoma of the skin, its diagnosis and therapeutic management still pose problems. OBJECTIVE: This study was undertaken to point out clinical and histopathologic features of verrucous carcinoma of the skin and to provide diagnostic and therapeutic guidelines on the basis of the long-term results from 20 patients. METHODS: A retrospective study of the long-term results of 20 patients treated surgically for verrucous carcinoma of the skin is presented. In 16 cases, a wide resection with histopathologic examination of the margins was possible. Two tumors were shaved; 1 case required below-knee amputation and 1 patient refused primary amputation. In April 1999, 9 of the 10 surviving patients underwent physical examination, ultrasonography of the regional lymph nodes and the abdomen, and chest X-ray. The protocols of autopsies or postmortem examinations of the deceased patients were consulted. RESULTS: The deceased patients achieved an average tumor-free survival period of 86.1 months; eight of the surviving patients had an average tumor-free follow-up of 127.4 months. Two patients suffered recurrences. CONCLUSION: Curative treatment can be achieved by timely and complete resection of verrucous carcinoma of the skin, even in advanced cases.

National survey of head and neck verrucous carcinoma: patterns of presentation, care, and outcome.

BACKGROUND: Verrucous carcinoma is distinguished by controversy regarding appropriate diagnosis and treatment. This study provides a contemporary survey of demographics, patterns of care, and outcome for this disease in the United States. METHODS: The National Cancer Data Base had 2350 cases of verrucous carcinoma of the head and neck diagnosed between 1985 and 1996. Statistical procedures included chi-square analyses, Student t tests, and relative survival. RESULTS: Tumors originated most frequently in the oral cavity (55.9%) and larynx (35.2%). Although most patients were male (60.0%), oral cavity tumors were more common among older females. The most prevalent treatment was surgery alone (69.7%), followed by surgery combined with irradiation (11.0%) and irradiation alone (10.3%). For oral cavity tumors, surgery alone was more common among early (85.8%) than advanced cases (56.9%); a larger proportion of advanced disease received radiation alone or surgery and irradiation combined. Most laryngeal tumors were treated with surgery (60.3% for early and 55.6% for advanced disease), but a higher proportion received radiation alone or surgery combined with radiation compared with oral cavity cases. Five-year relative survival was 77.9%. For localized disease, survival after surgery was 88.9% compared with 57.6% after irradiation. CONCLUSIONS: Demographic differences implicate different mechanisms of carcinogenesis for verrucous carcinoma arising in the oral cavity and the larynx. Although selection bias may account for the differences observed, patients receiving initial treatment with surgery had better survival than those treated with irradiation, especially for cases originating in the oral cavity.

Impact of phenotype on treatment and prognosis of laryngeal malignancies.

An overview of the impact of the phenotype on treatment and prognosis of different laryngeal malignancies is presented.