BACKGROUND AND PURPOSE: When treated by radiotherapy, patients with squamous cell carcinomas of the head and neck (HNSCC) positive for HPV and p16(INK4a) possess a clearly favorable prognosis as compared to those with HPV-negative HNSCC. The aim of this work was to study whether the better outcomes might be caused by an enhanced cellular radiosensitivity. MATERIALS AND METHODS: The radiation response of five HPV/p16(INK4a)-positive and five HPV-negative cell lines was characterized with regard to cellular radiosensitivity by colony formation assay. Furthermore G1- and G2-arrest, apoptosis and residual DNA double-strand breaks (DSB) were analyzed by the colcemid-based G1-efflux assay, propidium iodide staining, the detection of PARP cleavage, the fluorescence-based detection of caspase activity and the immunofluorescence staining of γH2AX and 53BP1 foci. RESULTS: On average, the cellular radiosensitivity of the HNSCC cell lines positive for HPV and p16(INK4a) was higher as compared to the sensitivity of a panel of five HPV-negative HNSCC cell lines (SF3=0.2827 vs. 0.4455). The higher sensitivity does not result from increased apoptosis or the execution of a permanent G1-arrest, but is rather associated with both, elevated levels of residual DSBs and extensive G2-arrest. CONCLUSIONS: Increased cellular radiosensitivity due to compromised DNA repair capacity is likely to contribute to the improved outcome of patients with HPV/p16(INK4a)-positive tumors when treated by radiotherapy.
BACKGROUND AND PURPOSE: When treated by radiotherapy, patients with squamous cell carcinomas of the head and neck (HNSCC) positive for HPV and p16(INK4a) possess a clearly favorable prognosis as compared to those with HPV-negative HNSCC. The aim of this work was to study whether the better outcomes might be caused by an enhanced cellular radiosensitivity. MATERIALS AND METHODS: The radiation response of five HPV/p16(INK4a)-positive and five HPV-negative cell lines was characterized with regard to cellular radiosensitivity by colony formation assay. Furthermore G1- and G2-arrest, apoptosis and residual DNA double-strand breaks (DSB) were analyzed by the colcemid-based G1-efflux assay, propidium iodide staining, the detection of PARP cleavage, the fluorescence-based detection of caspase activity and the immunofluorescence staining of γH2AX and 53BP1 foci. RESULTS: On average, the cellular radiosensitivity of the HNSCC cell lines positive for HPV and p16(INK4a) was higher as compared to the sensitivity of a panel of five HPV-negative HNSCC cell lines (SF3=0.2827 vs. 0.4455). The higher sensitivity does not result from increased apoptosis or the execution of a permanent G1-arrest, but is rather associated with both, elevated levels of residual DSBs and extensive G2-arrest. CONCLUSIONS: Increased cellular radiosensitivity due to compromised DNA repair capacity is likely to contribute to the improved outcome of patients with HPV/p16(INK4a)-positive tumors when treated by radiotherapy.
Authors: Christina A Wicker; Brian G Hunt; Sunil Krishnan; Kathryn Aziz; Shobha Parajuli; Sarah Palackdharry; William R Elaban; Trisha M Wise-Draper; Gordon B Mills; Susan E Waltz; Vinita Takiar Journal: Cancer Lett Date: 2021-01-12 Impact factor: 8.679
Authors: C Cleary; J E Leeman; D S Higginson; N Katabi; E Sherman; L Morris; S McBride; N Lee; N Riaz Journal: Clin Oncol (R Coll Radiol) Date: 2016-04-01 Impact factor: 4.126
Authors: Frank Ziemann; Andrea Arenz; Stefanie Preising; Claus Wittekindt; Jens P Klussmann; Rita Engenhart-Cabillic; Andrea Wittig Journal: Am J Cancer Res Date: 2015-02-15 Impact factor: 6.166
Authors: Michael Baumann; Mechthild Krause; Jens Overgaard; Jürgen Debus; Søren M Bentzen; Juliane Daartz; Christian Richter; Daniel Zips; Thomas Bortfeld Journal: Nat Rev Cancer Date: 2016-03-18 Impact factor: 60.716
Authors: Grace C Blitzer; Molly A Smith; Stephen L Harris; Randall J Kimple Journal: Int J Radiat Oncol Biol Phys Date: 2014-03-15 Impact factor: 7.038