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Atypical squamous cells of undetermined significance. Current laboratory practices of participants in the College of American Pathologists Interlaboratory. Comparison Program in Cervicovaginal Cytology.

OBJECTIVE: To evaluate current laboratory practices and rates for atypical squamous cells of undetermined significance (ASCUS), a category of epithelial cell abnormality in the Bethesda System. DESIGN: Questionnaire surveys were mailed in December 1993 and March 1994. SETTING: Cytopathology laboratory participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology (PAP). RESULTS: Most responding laboratories (82.5%) limited the use of "atypia" terminology to abnormalities of undetermined significance. Nearly half of the laboratories employed only the term ASCUS for squamous epithelial changes in this category. The median rate of ASCUS in 1993 was 2.8%, with 10% of laboratories reporting rates greater than 9.0%. The median squamous intraepithelial lesion rate was 2.0%, with a median ASCUS-squamous intraepithelial lesion ratio of 1.3. The majority of laboratories qualified a portion of ASCUS cases and issued recommendations for follow-up when appropriate. Fifty-six percent of laboratories surveyed included patients diagnosed with ASCUS in follow-up programs. Laboratories estimated that about 20% (median response) of patients with ASCUS smears had a squamous intraepithelial lesion or equivalent diagnosis made within a year's follow-up. CONCLUSIONS: The ASCUS category is used by the majority of laboratories as recommended by the Bethesda System, but reporting rates vary. The results of this survey and associated surveys provide laboratories with useful benchmark figures for interlaboratory comparison of ASCUS practices.

Cervix Uteri↗

Expression and function of squamous cell carcinoma antigen.

Squamous cell carcinoma antigen (SCCA) has been used as a promising aid for the management of squamous cell carcinoma of various sites. Recently, SCCA gene has been demonstrated at the 18q21.3 locus, and the exon sequence of SCCA gene shows a close homology with inhibitory-type serpins. Actually, SCCA inhibits human chymotrypsin, papain, calpain 1, or cathepsin L. Since serpins are involved in the intercellular adhesion events, it is likely that SCCA takes some part in the malignant behavious of squamous cancer, e.g. invasion or metastasis. SCCA is also present in the spinous and granular compartments of the mature squamous epithelium. Southern blot analysis of the SCCA gene in several vertebrates reveals that it is present in most of the eutherian species, but not in the metatheria, bird, reptile, amphibian or teleost. Thus, SCCA appears to play important roles in the stratification or differentiation of the integument. The present paper describes the expression and function of SCCA, and discusses its possible role in the biological behavious of malignant and nonmalignant squamous cells.

Amino Acid Sequence↗

Squamous papilloma of the esophagus.

BACKGROUND: Squamous papilloma of the esophagus (SPE) is a rare lesion, with a prevalence of 0.01% to 0.04%. This study was to assess the incidence, symptoms, signs and prognosis of squamous papilloma of the esophagus. METHODS: From October 1981 to October 1994, 124,000 patients at our hospital were examined with panendoscopy; 9 (0.0073%) subjects were histologically proved to have squamous papilloma of the esophagus. RESULTS: They included 4 males and 5 females, aged 60.8 +/- 9.7 years, ranging from 49 to 78 years old. These tumor locations were seven in the lower, one in the middle and one in the upper portion of the esophagus; sizes were not larger than 5 mm. Most of them were single (seven of nine) and sessile (eight of nine). Three of them were followed up with panendoscopy and six of them were followed up through clinical symptoms. The longest follow-up period were 11 years. The mean following time was 2.2 +/- 3.6 years. CONCLUSIONS: All of the patients are alive, and none has malignancy in the SPE. It is suggested that squamous papilloma of the esophagus may have a benign clinical course. Symptoms and signs are thought to be associated with gastroesophageal reflux or peptic ulcer diseases, and not to be related to the squamous cell papilloma itself.

Aged↗

MR differentiation of adamantinous and squamous-papillary craniopharyngiomas.

PURPOSE: To determine MR criteria for differentiating adamantinous from squamous-papillary craniopharyngiomas. METHODS: The MR imaging features of 42 histologically proved craniopharyngiomas (25 adamantinous, 15 squamous-papillary, and two mixed subtypes) were examined with multiplanar T2-weighted and noncontrast and contrast-enhanced T1-weighted imaging. Differences in the mR features of both subtypes were evaluated retrospectively. RESULTS: The adamantinous craniopharyngioma is a mixed solid-cystic or mainly cystic lobulated suprasellar or intrasellar/suprasellar tumor occurring in children and adults, typically with large nonenhancing hyperintense cysts on T1-weighted images. The squamous-papillary craniopharyngioma is a predominantly solid or mixed solid-cystic suprasellar tumor occurring in adults, appearing as a hypointense cyst on noncontrast T1-weighted images. Calcifications and recurrent tumors are more often observed in adamantinous tumors but can be seen in squamous-papillary tumors as well. Statistically significant parameters useful for differentiating the two tumor subtypes are the encasement of vessels, the lobulated shape, and the presence of hyperintense cysts in adamantinous tumors, and the round shape, the presence of hypointense cysts, and the predominantly solid appearance in squamous-papillary tumors. CONCLUSION: Craniopharyngiomas can be divided into two clinically, histologically different subtypes, which suggests a different pathogenesis of these two types of tumor.

Adolescent↗

Loss of a novel mucin-like epithelial glycoprotein in oral and cervical squamous cell carcinomas.

Stratified squamous epithelia of oral and cervical mucosa express high levels of simple mucin-type O-linked carbohydrates, and these are known to undergo structural changes in relation to epithelial differentiation and neoplastic transformation. O-glycans in these epithelia are associated with the cell membrane, but the identity of the carrier molecule(s) remains largely unknown. We report here the identification of a membrane-bound M(r) 200,000-250,000 glycoprotein (gp230) that is expressed in stratified squamous epithelia of the oral cavity. Western blot analysis identified gp230 as a major carrier of simple-mucin type carbohydrate antigens in buccal nonkeratinized mucosal epithelium, suggesting that it may represent a mucin-like molecule. A monoclonal antibody PANH4 defining a protein epitope of gp230 was generated. The PANH4 epitope was localized by immunohistology to suprabasal cell layers of buccal epithelium and was also found in larynx, esophagus, vagina, and exocervix, but not in epidermis. Data showed that gp230 was distinct from MUC1 or CD44. It is interesting that in most cases gp230 was not expressed in squamous cell carcinomas of buccal and cervical mucosa. A few moderately differentiated carcinomas, mainly from cervix, expressed the gp230 epitope. The results suggest that a membrane-bound mucin-like molecule, gp230, is associated with the differentiated phenotype of normal mucosal stratified squamous epithelia and that expression of gp230 generally is lost in severe oral epithelial dysplasia and squamous cell carcinomas of oral and cervical mucosa.

Adult↗

Cross-Platform Methylation-Based Site of Origin Classification for Squamous Cell Carcinomas.

Squamous cell carcinomas (SCCs) are one of the most common cancer types and can arise at nearly any anatomic site. Because SCCs are one of the most common metastases, do not have reliable site-specific morphologic or genomic features, and have considerable morphologic and immunohistochemical overlap with urothelial carcinomas, distinguishing between primary and metastatic squamous-appearing tumors can be challenging. This distinction can be critical to clinical management. We present Squamous cell carcinoma Methylation for Origin Site (SquaMOS), a methylation-based classifier to predict site of origin of squamous-appearing carcinomas. Trained on publicly available array-based methylation data from 1062 primary SCCs (from lung, head and neck, cervix, and esophagus) and urothelial carcinomas, SquaMOS predicted site of origin in primary tumors with 96.1% accuracy in an internal test set (n = 458) and 97.4% accuracy in an external test set from 3 institutions (n = 78). On metastatic tumors (n = 51), SquaMOS predictions were 96.1% accurate. SquaMOS was directly applicable to shallow Nanopore sequencing data (CpG probe site coverage, 0.25-2.88×) with an accuracy of 91.7% (n = 36; 100% accurate for high-confidence predictions). When tested on SCCs outside the training set types (n = 15, including 3 metastases to lung), no cases were misclassified as of lung origin, supporting accuracy of lung vs nonlung origin classification for diverse SCC types. Overall, we demonstrate highly accurate performance of the SquaMOS classifier on primary and metastatic tumors from multiple data sources, robust to suboptimal tumor purity. We illustrate transferability of our array-based classifier to low-depth Nanopore sequencing data, a potentially rapid means of site of origin determination in a clinical setting.

Humans↗

Special concern about squamous cell carcinoma of the scalp in organ transplant recipients.

BACKGROUND: Several risk factors are generally accepted to portend more aggressive behavior of cutaneous squamous cell carcinoma. These include tumor size, tumor depth, histologic subtype, location on the lip or ear, tumor arising in scar, recurrent tumor, and tumor demonstrating perineural invasion. Organ transplant recipients can have significant morbidity and mortality from squamous cell carcinoma. OBSERVATIONS: Four organ transplant recipients developed metastatic disease from squamous cell carcinoma of the scalp. CONCLUSIONS: Squamous cell carcinoma of the scalp in organ transplant recipients should be considered a high-risk tumor because of its anatomic location. Margin-controlled tumor extirpation, sentinel lymph node biopsy, and adjuvant radiation therapy should all be considered in the organ transplant recipient population.

Adult↗

Malignant tumors of the eyelid: a population-based study of non-basal cell and non-squamous cell malignant neoplasms.

OBJECTIVE: To determine the relative frequencies, average annual incidences, and patient characteristics of non-basal cell and non-squamous cell malignant neoplasms of the eyelid in a defined geographic population. DESIGN AND SETTING: A retrospective study using the Florida Cancer Data System to identify malignant tumors of the eyelid, except for basal cell and squamous cell carcinomas, from 1981 through 1994. Cases were limited to persons who resided within Florida. MAIN OUTCOME MEASURE: Incidence of histologically confirmed malignant eyelid tumors. RESULTS: Two hundred six primary malignant eyelid tumors were identified. The 3 most common, in order of frequency, were melanoma, sebaceous carcinoma, and lymphoma. The median age at diagnosis for all patients was 73 years. Only 3 of the 206 malignant neoplasms occurred in blacks. The annual incidence of eyelid melanoma and sebaceous carcinoma in whites older than 20 years was 0.6 and 0.5 per million, respectively. Kaposi sarcoma was the most common type of mesenchymal tumor. Eleven different histologic types of lymphoma were found in the eyelid. Only 2 of 27 lymphomas had T-cell lineage. CONCLUSIONS: Malignant tumors of the eyelid other than basal cell and squamous cell carcinoma are uncommon and usually occur in elderly white persons. Primary eyelid tumors of any type are rare in blacks. The risk of a non-basal cell and non-squamous cell malignant neoplasm of the eyelid in Florida is 6.4 times greater for whites than for blacks (95% confidence interval [CI], 2.1-20.2). A variety of B-cell lymphomas can be manifested as primary eyelid tumors.

Adenocarcinoma, Sebaceous↗

Simple predictors of survival in head and neck squamous cell carcinoma.

OBJECTIVE: To develop a simple prognostic survival rule from easily obtained characteristics of patients undergoing potentially curative resection of head and neck squamous cell carcinoma using classification and regression trees. DESIGN: Inception cohort. SETTING: Tertiary care center. PATIENTS: Consecutive patients undergoing resection lasting at least 2 hours, from July 1993 through June 1997. MAIN OUTCOME MEASURE: Survival, age, TNM tumor stage, functional class, systolic and diastolic blood pressure, body mass index, and serum albumin concentration were evaluated as predictors. RESULTS: Four hundred six patients were followed up for 5 to 1446 days (median, 391 days), during which time 172 deaths occurred. Median survival was 687 days. Patients with TNM stage I, II, or III squamous cell carcinoma had a mean survival of 1068 days. Patients with TNM stage IV or recurrent disease were further stratified. Those with a serum albumin concentration less than 3.85 g/dL had a median survival of 404 days (95% confidence interval, 286-532 days), and those with an serum albumin concentration of 3.85 g/dL or above had a median survival of 625 days (95% confidence interval, 536-1032 days). A similar survival was found using age younger than 66.5 years as a predictor instead of serum albumin concentration less than 3.85 g/dL. CONCLUSIONS: At our institution, patients with stage I, II, or III squamous cell carcinoma had a mean survival of approximately 3 years. Those with stage IV or recurrent squamous cell carcinoma could be stratified by either serum albumin concentration or by age into 2 groups with a median survival of 1 or 2 years.

Adult↗

Impact of retropharyngeal lymph node metastasis in head and neck squamous cell carcinoma.

BACKGROUND: The impact of metastasis to the retropharyngeal lymph node (RPLN) group is poorly understood because of the difficult access of the retropharyngeal space. Previous studies concluding to the negative impact of RPLN metastasis rely heavily on radiographic assessment, which introduces the possibility of diagnostic error. OBJECTIVE: To better define the prognostic significance of metastatic retropharyngeal adenopathy in patients with non-nasopharyngeal squamous cell carcinoma of the head and neck. STUDY DESIGN: A retrospective cohort study of patients with non-nasopharyngeal squamous cell carcinoma of the head and neck who underwent resection of the RPLN group and were followed up for an average of 24 months. SETTING: Tertiary care academic medical center. PATIENTS: The 51 patients included in the study had been treated for advanced-stage squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and/or supraglottic larynx via a surgical approach to the primary tumor that afforded access to the RPLN group. All patients underwent dissection and pathologic interpretation of the RPLNs, most patients received postoperative radiotherapy, and 43 patients met survival analysis criteria. MAIN OUTCOME MEASURES: Local and regional recurrence rates, the development of distant metastasis, and disease-free and overall survival. RESULTS: Metastasis to the RPLN group was confirmed pathologically in 14 (27.5%) patients. There was no statistically significant difference between patients with and without RPLN metastasis in rates of local recurrence (24.8% vs 28.4%), regional recurrence (17.5% vs 19.6%), distant metastasis (17.0% vs 11.2%), disease-free survival (40.5% vs 30.5%), and overall survival (40.6% vs 38.5%). CONCLUSION: Metastasis to the RPLN group does not impact disease control or survival in patients with advanced non-nasopharyngeal squamous cell carcinoma of the head and neck treated with multimodality therapy.

Adult↗

Phase 2 bioadjuvant study of interferon alfa-2a, isotretinoin, and vitamin E in locally advanced squamous cell carcinoma of the head and neck: long-term follow-up.

OBJECTIVE: To evaluate the long-term effects of the combination of isotretinoin, interferon alfa-2a, and vitamin E in locally advanced squamous cell carcinoma of the head and neck. DESIGN: Phase 2 prospective study. SETTING: Tertiary care academic medical centers. PATIENTS: Forty-five patients entered this study. All patients had stage III or IV squamous cell carcinoma of the head and neck and had been treated with surgical resection, radiation, or both. All patients were then treated with bioadjuvant chemopreventive treatment for 12 months. We previously reported a 24-month median follow-up of this phase 2 trial of the combination of isotretinoin, interferon alfa-2a, and vitamin E as bioadjuvant therapy after definitive local therapy. In that study, all 45 patients completed treatment, but 1 patient was excluded from analysis of recurrence and development of second primary tumors. Main Outcome Measure Longer-term (49.4-month median) follow-up. RESULTS: Among the 45 patients treated under the protocol, only 7 patients (16%) had died. Nine (20%) of 45 patients experienced progressive disease. Only 1 second primary tumor (acute promyelocytic leukemia) occurred during follow-up, and no aerodigestive second primary tumors occurred among the 45 patients. The 5-year progression-free survival and overall survival percentages were 80% (95% confidence interval, 65.1%-89.1%) and 81.3% (95% confidence interval, 63.7%-90.9%), respectively. These results are significantly better than the historical 5-year overall survival for advanced squamous cell carcinoma of the head and neck (approximately 40%). CONCLUSION: The bioadjuvant combination is highly effective in preventing recurrence and second primary tumors, and its role as standard therapy in advanced squamous cell carcinoma of the head and neck is being investigated in a randomized phase 3 study.

Antineoplastic Agents↗

Chemosensitivity and DNA ploidy in head and neck squamous cell carcinomas.

The succinate dehydrogenase activity and cellular DNA content of human head and neck squamous cell carcinomas were examined, and the chemosensitivity and ploidy status were compared with histologic differentiation. The average decrease of enzyme activity in the poorly differentiated squamous cell carcinomas was significantly greater than that of well- and moderately differentiated squamous cell carcinomas. Statistically significant differences were also noted with relation to the original site of the primary tumor. The chemosensitivity of a tumor with DNA aneuploidy tended to be lower among the well- and moderately differentiated squamous cell carcinomas and higher among the poorly differentiated type. We conclude from this study that simultaneous analysis of the chemosensitivity and DNA ploidy will aid not only in selecting effective antitumor drugs but also in predicting changes in cellular characteristics during the course of disease.

Antineoplastic Agents↗

Inhibition of growth of a murine squamous cell carcinoma by a cyclooxygenase inhibitor increases leukotriene B4 production.

OBJECTIVE: To determine the role of metabolites of arachidonic acid in the growth of squamous cell carcinomas of the head and neck. DESIGN: Investigation of the effect of a cyclooxygenase inhibitor, piroxicam, on the growth of squamous cell carcinoma in a murine model. INTERVENTION: C3H/HeJ mice bearing squamous cell carcinoma (SCCVII) were treated with piroxicam (0.08 mg/d, orally) for 30 days beginning 1 day before tumor inoculation. MAIN OUTCOME MEASURES: Decrease in tumor volumes and tumor growth rates. RESULTS: Significant inhibition of tumor growth (P = .002) and final tumor weight (P = .0007) was noted in the group receiving piroxicam therapy. Prostaglandin E2 levels in the tumor tissue were unrelated to treatment or tumor size. Increased levels of leukotriene B4 were observed in the piroxicam-treated group (P = .03), and larger tumors were associated with decreased leukotriene B4 levels (P = .0001). CONCLUSIONS: Cyclooxygenase inhibitors may be effective in the treatment of some squamous cell carcinomas. The therapeutic effect of cyclooxygenase inhibitors may result from shunting into the lipoxygenase pathway of arachidonic acid metabolism.

Animals↗

Interleukins 2 and 12 activate natural killer cytolytic responses of peripheral blood mononuclear cells from patients with head and neck squamous cell carcinoma.

OBJECTIVES: To examine the capacity of interleukin-2 (IL-2) and interleukin-12 (IL-12) to modulate the cytolytic activity of peripheral blood mononuclear cells against squamous cell carcinoma, and to determine whether peripheral blood mononuclear cells from healthy donors respond differently to IL-12 than do peripheral blood mononuclear cells from patients with head and neck squamous cell carcinoma. DESIGN: Case-comparison study of a consecutive sample of patients with head and neck squamous cell carcinoma who were scheduled to undergo surgical excision. PARTICIPANTS: The study included 10 patients with stage III or IV carcinoma matched with 10 volunteer blood donors. INTERVENTION: Isolated peripheral blood mononuclear cells from patients and volunteers were treated with IL-2, 10 U/mL and 100 U/mL; IL-12, 1 U/mL or 10 U/mL; or a combination of IL-2 and IL-12. RESULTS: The combination of IL-2 and IL-12 consistently produced the greatest activation cytolysis than either cytokine alone at all concentrations tested. This increased activity against a squamous cell carcinoma cell line was seen in lymphocytes from volunteers and patients. CONCLUSION: Our findings suggest a new treatment regimen for the patient with head and neck cancer that uses immunomodulation with a combination of cytokines.

Aged↗

Evaluation of prevertebral muscle invasion by squamous cell carcinoma. Can computed tomography replace open neck exploration?

OBJECTIVE: To compare computed tomography (CT) with open neck exploration in determining prevertebral invasion by squamous cell carcinoma of the oropharynx or hypopharynx. DESIGN: Retrospective analysis using the findings at open neck exploration and results of histopathologic studies as the criterion standards. SETTING: Tertiary care referral center. PATIENTS: Twenty-nine of 40 patients with advanced squamous cell carcinoma of the oropharynx or hypopharynx treated between January 1, 1986, and December 31, 1994, were selected for analysis based on CT findings of posterolateral extension of the primary tumor placing the prevertebral muscle (PVM) at risk. All study patients had no previous therapy and underwent neck exploration to determine resectability. RESULTS: Overall accuracy of CT in predicting PVM status was 55.2%. The sensitivity of preoperative CT for PVM invasion was 50%; the specificity was 61%. Using an estimate of 21% for the prevalence of PVM invasion, the predictive value of a positive CT scan was 0.254 and the predictive value of a negative CT scan was 0.821. Open neck exploration correctly predicted PVM status in all cases. CONCLUSIONS: Open neck exploration is superior to CT to evaluate possible PVM invasion by squamous cell carcinoma of the oropharynx or hypopharynx. The predictive value of a negative CT scan for PVM invasion is high, so it may be useful in treatment planning. Patients with advanced squamous cell carcinoma of the oropharynx or hypopharynx at risk for PVM invasion who are otherwise surgical candidates should be considered for open neck exploration to determine resectability most accurately.

Adult↗

HSV-tk gene therapy in head and neck squamous cell carcinoma. Enhancement by the local and distant bystander effect.

OBJECTIVES: To determine whether the bystander effect demonstrated in vitro for ganciclovir-mediated killing of a herpes simplex virus thymidine kinase (HSV-tk) gene-infected human squamous cell carcinoma is operative in vivo in a nude mouse model. DESIGN: Prospective study in a murine model. INTERVENTION: Human head and neck squamous cell carcinoma tumors were grown as xenografts on the flanks of 20 nude mice. The tumors in the left flank were then infected with the HSV-tk gene. Then, after 48 hours, the animals were treated with intraperitoneal ganciclovir twice daily. Assessment of the tumors on both flanks was performed over a 31-day period. MAIN OUTCOME MEASURES: Resolution of tumors infected with HSV-tk gene in animals treated with ganciclovir; resolution of tumors uninfected with HSV-tk gene on the contralateral flank in animals treated with ganciclovir. RESULTS: Following HSV-tk gene therapy in nude mice, complete resolution of HSV-tk-gene-infected human head and neck squamous cell carcinoma tumors was observed following ganciclovir treatment. Uninfected tumors were also noted to regress, but not completely resolve, in response to intraperitoneal ganciclovir (distant bystander effect). CONCLUSIONS: This study confirms that the local and distant bystander effects exist in this murine model, enhancing the possibility of its role for treatment of human squamous cell carcinoma of the head and neck.

3T3 Cells↗

Absence of p53 mutations in squamous carcinomas of the tongue in nonsmoking and nondrinking patients younger than 40 years.

BACKGROUND: Although carcinoma of the tongue usually occurs in patients older than 60 years, up to 4% of these tumors may occur in patients younger than 40 years. Many of the younger patients with this tumor have had no exposure or brief exposure to tobacco smoke or alcohol consumption, to which oral carcinoma is usually attributed. The molecular mechanism responsible for carcinogenesis in this group of patients is not known. OBJECTIVE: To assess the role of p53 gene mutation in oral carcinogenesis in a group of patients younger than 40 years with squamous carcinoma of the tongue. DESIGN: Squamous carcinoma cells were isolated from paraffin blocks by microdissection. DNA extracted from these cells was tested for the presence of p53 mutations by polymerase chain reaction and single-stranded conformational polymorphism analysis. Mutations identified by this procedure were directly sequenced. Sections of the tumors were also stained using an immunoperoxidase immunohistochemical technique for expression of p53 protein. SUBJECTS: Eleven patients were selected on the basis of 2 criteria: presence of squamous cell carcinoma and age younger than 40 years. Six of the 11 patients had no history of measurable tobacco or alcohol exposure. RESULTS: Two mutations were detected among 11 tumors by single-stranded conformational polymorphism analysis, one in exon 4 and a second in exon 7. The former mutation consisted of G:C to C:G (guanine:cytosine to cytosine:guanine) transition in codon 72 (CGC to CCC), which would have resulted in the substitution of a proline residue for arginine. With the immunoperoxidase immunohistochemical technique for p53 protein, strong, diffuse nuclear staining was observed only in this tumor. The second mutation was a G:C to A:T (guanine:cytosine to adenine:thymine) transition in codon 248 (CGG to CGA), which would have resulted in no amino acid change since both mutant and wildtype codon sequences encode arginine. Weaker and more variable anti-p53 immunostaining was noted in this and 4 other tumors. Five tumors were negative for p53 protein by the immunoperoxidase immunohistochemical technique. CONCLUSIONS: Our results suggest that p53 gene mutations are less frequent in squamous carcinomas occurring in nonsmoking young patients who do not drink alcohol than in young smokers or in the general population. Paucity of p53 mutations may be explained by the absence of exposure to tobacco smoke or alcohol. These data leave unanswered the question of the molecular mechanism responsible for oral carcinogenesis in this group of patients and suggest that this group may be a suitable population in which to study genetic susceptibility to aerodigestive carcinoma isolated from the confounding factors of tobacco and alcohol exposure.

Adult↗

Human papillomavirus in head and neck squamous cell carcinomas in nonsmokers.

OBJECTIVE: To establish relationships between smoking status and human papillomavirus in head and neck squamous cell carcinomas. DESIGN: Human papillomavirus was detected in paraffin-embedded samples using E6-directed consensus primers and type-specific oligonucleotide probes. Patients were classified as smokers and nonsmokers. Alcohol use was also recorded. Data were analyzed by means of the Fisher exact test. Sequence analysis of exons 5 to 8 of the p53 gene was performed in tumor samples from nonsmokers. SETTING: Academic medical center in Paris, France. PATIENTS: One hundred eighty-seven consecutive patients with head and neck squamous cell carcinoma. RESULTS: The overall prevalence of human papillomaviral infection was 10.7%. Human papillomavirus occurred more frequently (P = .02) in oropharyngeal squamous cell carcinoma (18.6%) than in other locations (6.1%). There were 10 nonsmokers (5%). The 50% incidence of human papillomavirus in nonsmokers (95% confidence interval, 19%-81%) differed significantly from the 8.5% incidence in smokers (95% confidence interval, 5%-14%; P = .003). No occupational risk factor was recorded in nonsmokers. None of these patients had p53 gene mutations in cancer cells. CONCLUSION: These findings suggest that human papillomavirus may play a role in head and neck squamous cell carcinomas in nonsmokers.

Adult↗