***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Oropharyngeal squamous-cell carcinomas caused by human papillomavirus ( HPV ) are associated with favorable survival , but the independent prognostic significance of tumor HPV status remains unknown . METHODS We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a r and omized trial comparing accelerated-fractionation radiotherapy ( with acceleration by means of concomitant boost radiotherapy ) with st and ard-fractionation radiotherapy , each combined with cisplatin therapy  , in patients with squamous-cell carcinoma of the head and neck . Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer . RESULTS The median follow-up period was 4.8 years . The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving st and ard-fractionation radiotherapy ( 70.3 % vs. 64.3 % ; P=0.18 ; hazard ratio for death with accelerated-fractionation radiotherapy , 0.90 ; 95 % confidence interval [ CI ] , 0.72 to 1.13 ) , as were the rates of high- grade acute and late toxic events . A total of 63.8 % of patients with oropharyngeal cancer ( 206 of 323 ) had HPV-positive tumors ; these patients had better 3-year rates of overall survival ( 82.4 % , vs. 57.1 % among patients with HPV-negative tumors ; P<0.001 by the log-rank test ) and , after adjustment for age , race , tumor and nodal stage , tobacco exposure , and treatment assignment , had a 58 % reduction in the risk of death ( hazard ratio , 0.42 ; 95 % CI , 0.27 to 0.66 ) . The risk of death significantly increased with each additional pack-year of tobacco smoking . Using recursive-partitioning analysis , we classified our patients as having a low , intermediate , or high risk of death on the basis of four factors : HPV status , pack-years of tobacco smoking , tumor stage , and nodal stage . CONCLUSIONS Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer . ( Clinical Trials.gov number , NCT00047008 . PURPOSE The phase III Iressa Survival Evaluation in Lung Cancer ( ISEL ) trial compared gefitinib with placebo in 1,692 patients with refractory advanced non-small-cell lung cancer . We analyzed ISEL tumor biopsy sample s to examine relationships between biomarkers and clinical outcome after gefitinib treatment in a placebo-controlled setting . METHODS Biomarkers included epidermal growth factor receptor ( EGFR ) gene copy number by fluorescence in situ hybridization ( n = 370 ) ; EGFR ( n = 379 ) and phosphorylated Akt ( p-Akt ) protein expression ( n = 382 ) by immunohistochemistry ; and mutations in EGFR ( n = 215 ) , KRAS ( n = 152 ) , and BRAF ( n = 118 ) . RESULTS High EGFR gene copy number was a predictor of a gefitinib-related effect on survival ( hazard ratio [ HR ] , 0.61 for high copy number and HR , 1.16 for low copy number ; comparison of high v low copy number HR , P = .045 ) . EGFR protein expression was also related to clinical outcome ( HR for positive , 0.77 ; HR for negative , 1.57 ; comparison of high v low protein expression HR , P = .049 ) . Patients with EGFR mutations had higher response rates than patients without EGFR mutations ( 37.5 % v 2.6 % ) ; there were insufficient data for survival analysis . No relationship was observed between p-Akt protein expression and survival outcome , and the limited amount of data collected for KRAS and BRAF mutations prevented any meaningful evaluation of clinical outcomes in relation to these mutations . CONCLUSION EGFR gene copy number was a predictor of clinical benefit from gefitinib in ISEL . Additional studies are warranted to assess these biomarkers fully for the identification of patients most likely to benefit from gefitinib treatment PURPOSE We have previously shown that loss of BAX expression is a negative prognostic factor in metastatic colorectal cancer . In the present study , we addressed the prognostic relevance of BAX and its upstream regulator p53 in squamous cell carcinoma ( SCC ) of the esophagus . Analysis of p16(ink4a/CDKN2 ) was included because p16(ink4a/CDKN2 ) and p53 were shown previously to cooperate during induction of cell cycle arrest and apoptosis . PATIENTS AND METHODS Retrospective analysis of 53 patients with curative intended R0 resection of esophageal SCC was done .  Protein expression of BAX , p53 , and p16(ink4a/CDKN2 )  was investigated by immunohistochemistry . In addition , tumor DNA was screened for BAX frameshift mutations by fragment length analysis and for p53 mutations by single-str and conformation polymorphism-polymerase chain reaction . RESULTS Overall median survival was 13.7 months . Patients with high BAX protein expression had a median survival of 19.5 months versus 8.0 months with low BAX expression ( P < .005 ) . High p16(ink4a/CDKN2 ) protein expression was associated with a median survival of 23.8 months versus 9.7 months with low p16(ink4a/CDKN2 ) ( P = .011 ) . The best survival ( median , 45.8 months ) was seen in a subgroup of 12 patients whose tumors bore the combination of both favorite phenotypes ( ie , high BAX and high p16(ink4a/CDKN2 ) protein expression ) . CONCLUSION In this retrospective investigation , the combined analysis of BAX and p16(ink4a/CDKN2 ) shows subgroups in SCC of the esophagus with favorable ( p16(ink4a/CDKN2)/BAX high expressing ) or poor prognosis ( loss of p16(ink4a/CDKN2)/loss of BAX ) . We suggest that such a multimarker analysis of apoptosis pathways could be useful for individualization of therapeutic strategies in the future , and suggest prospect i ve studies to confirm these results Despite encouraging results with chemoradiation as the primary means of managing carcinoma of the anal canal , approximately 20 % of patients will develop a local recurrence . This study examined the prognostic significance of p53 nuclear protein overexpression in the pretreatment biopsies of patients treated with chemoradiation for epidermoid carcinoma of the anal canal Objectives : The incidence of anal cancer among men who have sex with men ( MSM ) has continued to increase since the introduction of highly active antiretroviral therapy ( HAART ) . The prevalence of the putative anal cancer precursor , anal intraepithelial neoplasia ( AIN ) was high among HIV-positive MSM prior to the availability of HAART but little is known about AIN since HAART was introduced . We characterized the prevalence of AIN among HIV-positive MSM and examined the association between AIN and various factors including use of HAART . Design and methods : A baseline point-prevalence analyses in a prospect i ve cohort study of AIN was performed at a university-based research clinic . A total of 357 HIV-positive MSM with no history of anal cancer completed a question naire detailing behaviors and medical history , anal cytology and human papillomavirus ( HPV ) testing , and high-resolution anoscopy with biopsy for detection of AIN . Results : Eighty-one percent of participants with available CD4 + cell counts at baseline had AIN of any grade ; 52 % had AIN 2 or 3 ; and 95 % had anal HPV infection . In multivariate analysis , detection of ≥ 6 HPV types [ odds ratio ( OR ) , 36 ; 95 % confidence interval ( CI ) , 7.4–171 ) and use of HAART ( OR , 10 ; 95 % CI , 2.6–38 ) were associated with AIN after adjustment for length of time participants were HIV-positive , CD4 + cell count and HIV viral load . Conclusions : The prevalence of AIN has remained high among HIV-positive MSM after the introduction of HAART . Our data indicate that HAART is not associated with a reduced prevalence of AIN and support measures to prevent anal cancer among HIV-positive MSM whether or not they are using HAART PURPOSE To assess the prognostic significance of p53 protein expression in patients with primary epidermoid carcinoma of the anal canal managed by radiation therapy ( XRT ) , 5-fluorouracil ( 5-FU ) , and mitomycin C ( MMC ) . METHODS AND MATERIAL S From January 1991 to December 1993 , 58 consecutive patients with primary epidermoid carcinoma of the anal canal were treated in a prospect ively design ed protocol of XRT ( 24 Gy/12 - -3(1/2 ) wk split--28 Gy/14 ) and concurrent 5-FU ( 1000 mg/m2/day 1 - 4 ) and MMC ( 10 mg/m2 day 1 ) of each cycle of XRT . Paraffin-embedded tumor sample s were unavailable in 9 patients , leaving 49 patients in the study .  Expression of p53 protein was studied using immunohistochemistry and quantified as percent tumor nuclei showing positive staining . Actuarial survival and disease-free survival ( DFS ) rates were estimated by the Kaplan-Meier method , and compared using the log-rank test . A Cox proportional hazard model was used for the multivariable analysis . RESULTS There were 6 T1 , 26 T2 , 7 T3 , and 10 T4 lesions . Primary tumor sizes ranged from 1 - 15 cm with a median of 4 cm . There were 6 patients with nodal metastases . Median follow-up was 4.5 years . Positive nuclear immunostaining for p53 was observed in 40 of 49 patients . The median percent positive staining was 5 % , with 13 , 9 , and 18 patients showing staining in < 5 % , 5 to < 10 % , and 10 - 50 % of tumor nuclei respectively . There was no correlation of percent p53 staining with gender , age , tumor stage , size , or histology . Local , regional , and distant failures were observed in 12 , 2 , and 2 patients respectively . The 5-yr survival and DFS were 84 % and 64 % respectively . In univariate analysis , the only prognostic variable for survival was gender . For DFS , advanced T category and large tumor size were predictive of poor DFS . In multivariate analysis , poor DFS was associated with high T category ( p = 0.0008 ) , basaloid histology ( p = 0.001 ) , male gender ( p = 0.002 ) , and increasing percent of p53 protein expression ( p = 0.01 ) . CONCLUSIONS It is concluded that expression for p53 protein is present in a high percentage of patients with epidermoid carcinoma of the anal canal . For patients managed with combined  XRT , 5-FU , and MMC , percent p53 protein expression is of prognostic value for DFS independent of other clinical factors such as T category , gender , and histology Ultimately aim ing at a more individualized therapeutic approach in epidermoid anal cancer , this study explored the prognostic and predictive impact of a set of tumour markers . From a population -based cohort of 276 patients with epidermoid anal cancer , treated according to prospect i ve protocol s , 215 pre-treatment biopsies were investigated using immunohistochemistry . The expression of p53 , p21 , Cyclin A and CD31 was measured semi-quantitatively . The expression rate was classified as high when immunostaining was seen in > 5 % of the tumour cells for p53 and p21 , > 20 % in Cyclin A and , above median vessel count for CD31 . Marker expression was correlated to survival and treatment response . A high Cyclin A expression correlated significantly with improved overall ( 77 % vs 59 % , p = 0.005 ) and tumour-specific ( 81 % vs 64 % , p = 0.009 ) survival at 5 years . Also , the locoregional failure rate was significantly lower in patients with a high Cyclin A expression ( 12 % vs 24 % , p < 0.05 ) . In a multivariate Cox analysis Cyclin A was an independent prognostic factor . A low p21 expression correlated with a reduced rate of locoregional failure ( 14 % vs 27 % , p < 0.05 ) but no impact on survival was found . For p53 and CD31 no significant correlations were obtained . Cyclin A may be an indicator of radiosensitivity and a valuable prognostic marker in epidermoid anal cancer PURPOSE Expression of Bcl-2 protein is associated with chemotherapy resistance and decreased survival in chronic lymphocytic leukemia ( CLL ) . We evaluated whether oblimersen would improve response to chemotherapy 
    Output:
    
Conclusions : An array of biomarkers have been identified that correlate with survival following chemoradiotherapy in anal cancer .
However , investigators are yet to identify a biomarker that has the ability to consistently predict outcome in this disease .