The presence of<unk>  within the tumour has been realised to be an important factor for predicting survival since the 1990s. Comparison with<unk> -negative<unk><unk>  Tumor<unk>  status is strongly associated with positive therapeutic response and survival compared with<unk> -negative<unk> , independent of the treatment modality chosen and even after adjustment for stage. While<unk> +OPC patients have a number of favourable demographic features compared to<unk> -OPC patients, such differences account for only about ten per cent of the survival difference seen between the two groups. Response rates of over 80% are reported in<unk> +<unk>  and three-year progression free survival has been reported as 75–82% and 45–57%, respectively, for<unk> + and<unk> -<unk> , and improving over increasing time. It is likely that<unk> +OPC is inherently less malignant than<unk> -OPC, since patients treated by surgery alone have a better survival after adjustment for stage. Determinants of survival In RTOG clinical trial 0129, in which all patients with advanced disease received radiation and chemotherapy, a retrospective analysis (recursive-partitioning analysis, or RPA) at three years identified three risk groups for survival (low, intermediate, and high) based on<unk>  status, smoking, T stage and N stage (see Ang et al., Fig. 2).<unk>  status was the major determinant of survival, followed by smoking history and stage. 64% were<unk> + and all were in the low and intermediate risk group, with all non-smoking<unk> + patients in the low risk group. 82% of the<unk> + patients were alive at three years compared to 57% of the<unk> - patients, a 58% reduction in the risk of death. Locoregional failure is also lower in<unk> +, being 14% compared to 35% for<unk> -. Determinants of disease progression<unk>  positivity confers a 50–60% lower risk of disease progression and death, but the use of tobacco is an independently negative prognostic factor. A pooled analysis of<unk> +OPC and<unk> -OPC patients with disease progression in RTOG trials 0129 and 0522 showed that although less<unk> +OPC experienced disease progression (23 v. 40%), the median time to disease progression following treatment was similar (8 months). The majority (65%) of recurrences in both groups occurred within the first year after treatment and were locoregional. Although the rate of failure in the opposite neck following treatment of only one side, is 2.4%, the rate of an isolated recurrence in the opposite neck is 1.7%, and these were mainly where the primary tumour involved the midline. However the rate of failure in the contralateral neck is also greater for<unk> +. Of those that recur in this site, nearly all were successfully treated (salvaged) by further local treatment to the opposite neck. Determinants of metastasis rates<unk> + did not reduce the rate of metastases (about 45% of patients experiencing progression), which are predominantly to the lungs (70%), although some studies have reported a lower rate. with 3-year distant recurrence rates of about 10% for patients treated with primary radiation or chemoradiation. Even if recurrence or metastases occur,<unk>  positivity still confers an advantage. By contrast tobacco usage is an independently negative prognostic factor, with decreased response to therapy, increased disease recurrence rates and decreased survival. The negative effects of smoking, increases with amount smoked, particularly if greater than 10 pack-years. Predictors of survival After chemoradiation For patients such as those treated on RTOG 0129 with primary chemoradiation, detailed nomograms have been derived from that dataset combined with RTOG 0522, enabling prediction of outcome based on a large number of variables. For instance, a 71 year old married non-smoking high school graduate with a performance status (PS) of 0, and no weight loss or anaemia and a T3N1<unk> +OPC would expect to have a progression-free survival of 92% at 2 years and 88% at 5 years. A 60 year old unmarried nonsmoking high school graduate with a PS of 1, weight loss and anaemia and a T4N2<unk> +OPC would expect to have a survival of 70% at two years and 48% at five years. After surgery Less detailed information is available for those treated primarily with surgery, for whom less patients are available, as well as low rates of recurrence (7–10%), but features that have traditionally been useful in predicting prognosis in other head and neck<unk> s, appear to be less useful in<unk> +OPC. These patients are frequently stratified into three risk groups: * Low risk: No adverse pathological features * Intermediate risk: T3–T4 primary, perineural or lymphovascular invasion, N2 (AJCC 7) * High risk: Positive margins, ECE Development of other<unk> s<unk> +OPC patients are less likely to develop other<unk> s, compared to other head and neck<unk>  patients. A possible explanation for the favourable impact of<unk> + is "the lower probability of occurrence of 11q13 gene amplification, which is considered to be a factor underlying faster and more frequent recurrence of the disease" Presence of TP53 mutations, a marker for<unk> - OPC, is associated with worse prognosis. High grade of p16 staining is thought to be better than<unk>  PCR analysis in predicting radiotherapy response. Regional recurrence after surgery The risk of regional<unk>  recurrence after neck dissection is often estimated from a large series based on all upper aerodigestive squamous cell<unk> s. In this series, the overall risks at three years by pathological stage (AJCC 7) were: *pN0 4.7% *pN1 4.9% *pN2 12.1%
HPV-positive oropharyngeal cancer
Tobacco
Hepatitis C and HIV coinfection
Branchial cleft cyst
Circumcision and HIV
Oral florid papillomatosis
Hormone receptor positive breast tumor
Human papillomavirus infection