Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis

Arenz, Andrea; Ziemann, Frank; Mayer, Christina; Wittig, Andrea; Dreffke, Kirstin; Preising, Stefanie; Wagner, Steffen; Klußmann, Jens Peter; Engenhart‐Cabillic, Rita; Wittekindt, Claus

doi:10.1007/s00066-014-0605-5

Cited by 99 publications

(114 citation statements)

References 39 publications

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“…This enhanced sensitivity was also demonstrated on the cellular level when comparing HPV(+) and HPV(−) HNSCC cell lines [9–12]. Since cisplatin is never administered in monotherapy and since only few preclinical data exist for HPV(+) HNSCC [13], it remains unclear whether HPV(+) tumors are also characterized by an enhanced cisplatin-sensitivity.…”

Section: Introductionmentioning

confidence: 98%

Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines

et al. 2016

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Patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) show better survival rates than those with HPV-negative HNSCC. While an enhanced radiosensitivity of HPV-positive tumors is clearly evident from single modality treatment, cisplatin is never administered as monotherapy and therefore its contribution to the enhanced cure rates of HPV-positive HNSCC is not known. Both cisplatin and radiotherapy can cause severe irreversible side effects and therefore various clinical studies are currently testing deintensified regimes for patients with HPV-positive HNSCC. One strategy is to omit cisplatin-based chemotherapy or replace it by less toxic treatments but the risk assessment of these approaches remains difficult. In this study we have compared the cytotoxic effects of cisplatin in a panel of HPV-positive and -negative HNSCC cell lines alone and when combined with radiation.While cisplatin-treated HPV-positive strains showed a slightly stronger inhibition of proliferation, there was no difference regarding colony formation. Cellular responses to the drug, namely cell cycle distribution, apoptosis and γH2AX-induction did not differ between the two entities but assessment of cisplatin-DNA-adducts suggests differences regarding the mechanisms that determine cisplatin sensitivity. Combining cisplatin with radiation, we generally observed an additive but only in a minority of strains from both entities a clear synergistic effect on colony formation. In summary, HPV-positive and -negative HNSCC cells were equally sensitive to cisplatin. Therefore replacing cisplatin may be feasible but the substituting agent should be of similar efficacy in order not to jeopardize the high cure rates for HPV-positive HNSCC.

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Section: Introductionmentioning

confidence: 98%

Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines

et al. 2016

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“…Explanations mentioned are, for example, increased radiosensitivity or enhanced antitumor immunological reactions. Increased radiosensitivity may be the result of differences in cell cycle progression or wild‐type non‐mutated p53 in HPV‐positive cells leading to more effective apoptosis . Enhanced antitumor immunological reactions may be the result of a decrease in surface expression of CD47 on the membrane of HPV‐positive cells.…”

Section: Introductionmentioning

confidence: 99%

Adverse effect of smoking on prognosis in human papillomavirus–associated oropharyngeal carcinoma

et al. 2016

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“…One of the explanations for this behaviour is the impaired DNA repair ability found among HPV-positive tumours and a considerable G 2 arrest. These experimental studies have shown that irradiated HPV-positive cells progress faster through the S phase and then accrue in G 2 /M [75]. This unusual behaviour alters the expected cellular distribution along the cell cycle, accumulating the HPV cells in the more radiosensitive phases.…”

Section: One Of the Known Risk Factors In Head And Neck Cancer Is Thementioning

confidence: 98%

“…A large number of studies have proven that head and neck cancers that are positive for HPV have higher cellular radiosensitivity than their non-HPV counterparts [74,75]. One of the explanations for this behaviour is the impaired DNA repair ability found among HPV-positive tumours and a considerable G 2 arrest.…”

Section: One Of the Known Risk Factors In Head And Neck Cancer Is Thementioning

confidence: 99%

The Six Rs of Head and Neck Cancer Radiotherapy

Marcu¹,

Toma-Daşu²,

Daşu³

2015

Contemporary Issues in Head and Neck Cancer Management

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Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis

Abstract: The enhanced responsiveness of HPV-related HNSCC to radiotherapy might be caused by a higher cellular radiosensitivity due to cell cycle dysregulation and impaired DNA DSB repair.

Cited by 99 publications

References 39 publications

Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines

Similar cisplatin sensitivity of HPV-positive and -negative HNSCC cell lines

Adverse effect of smoking on prognosis in human papillomavirus–associated oropharyngeal carcinoma

The Six Rs of Head and Neck Cancer Radiotherapy

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