Absent/weak CD44 intensity and positive human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma indicates a very high survival

Abstract

Patients with human papillomavirus DNA positive (HPVDNA+) oropharyngeal squamous cell carcinoma (OSCC) have better clinical outcome than those with HPV DNA negative (HPVDNA−) OSCC upon intensive oncological treatment. All HPVDNA+ OSCC patients may not require intensive treatment, however, but before potentially deintensifying treatment, additional predictive markers are needed. Here, we examined HPV, p16INK4a, and CD44 in OSCC in correlation to clinical outcome. Pretreatment tumors from 290 OSCC patients, the majority not receiving chemotherapy, were analyzed for HPV DNA by Luminex and for p16INK4a and CD44 by immunohistochemistry. 225/290 (78%) tumors were HPVDNA+ and 211/290 (73%) overexpressed p16INK4a, which correlated to presence of HPV (P < 0.0001). Presence of HPV DNA, absent/weak CD44 intensity staining correlated to favorable 3-year disease-free survival (DFS) and overall survival (OS) by univariate and multivariate analysis, and likewise for p16INK4a by univariate analysis. Upon stratification for HPV, HPVDNA+ OSCC with absent/weak CD44 intensity presented the significantly best 3-year DFS and OS, with >95% 3-year DFS and OS. Furthermore, in HPVDNA+ OSCC, p16INK4a+ overexpression correlated to a favorable 3-year OS. In conclusion, patients with HPVDNA+ and absent/weak CD44 intensity OSCC presented the best survival and this marker combination could possibly be used for selecting patients for tailored deintensified treatment in prospective clinical trials.Absence of/weak CD44 or presence of human papillomavirus (HPV) DNA was shown as a favorable prognostic factors in tonsillar and tongue base cancer. Moreover, patients with the combination of absence of/weak CD44 and presence of HPV DNA presented a very favorable outcome. Therefore, we suggest that this marker combination could potentially be used to single out patients with a high survival that could benefit from a de-escalated oncological treatment.

Relevant Role of Di-Fucosylated Ley Antigen in the Outcome of Locally Advanced Cervical Squamous Cell Carcinoma Patients Treated with Cisplatin Regimen

“…Among of tumors with viral cytopathic effect found in our series, we observed a predominant expression of CD44 and the phenotype CD44+/LeY-. Recently, Näsman et al observed in 290 oropharyngeal squamous cell carcinoma patients a poor DFS when the tumors had HPV+ and medium/strong CD44 intensity staining [38]. Also, Hufbauer et al showed in a cutaneous keratinocyte line PM1 that the expose to HVP lead to a shift of the total population from low toward higher CD44 cell surface expression and, in turn, pointed to a reduction in the number of terminally differentiated cells [39].…”

A model for predicting clinical outcome in patients with human papillomavirus-positive tonsillar and base of tongue cancer

“…LGII-intensity were coded as 0 if 'absent'; 1 if 'weak'; 2 if 'normal' and 3 if 'strong' [16,17]. Stage was coded as 0 if stage was I or II; 1 if stage was III; 2 if stage was IVa; 3 if stage was IVb; and 4 if stage was IVc.…”

“…Data were collected on patients diagnosed during 2000-2011 with HPV DNA positive tumour biopsies, 308 with TSCC (ICD-10 code C09.0-9) and 112 with BOTSCC (ICD-10 code C01.9), at Karolinska University Hospital [5,[16][17][18][19][20][21]. Radiotherapy (RT) was given up to 68 Gy in conventional or accelerated settings, with or without induction chemo-RT (CRT) (Cisplatin + 5FU with/without Docetaxel, or with/without Capecitabine).…”

“…Radiotherapy (RT) was given up to 68 Gy in conventional or accelerated settings, with or without induction chemo-RT (CRT) (Cisplatin + 5FU with/without Docetaxel, or with/without Capecitabine). When brachytherapy was used, a dose of 78 Gy was reached [16][17][18][19][20][21] …”

“…Age, stage and smoking, and some biomarkers influence HPV + OSCC outcome, and e.g. absent/low HLA class I, CD44, LMP10 expression, high LRIG1 expression, absence of HLA-A * 02 or high CD8 + tumour infiltrating lymphocyte (TIL) counts, predict high survival [14][15][16][17][18][19][20][21]. Lack of HLA class I expression correlated to very high survival predictability, but identified fewer patients, while high CD8 + TIL counts, identified more patients, but with slightly less probability of survival [16,21].…”