Abstract：Objective To investigate the association of human papilloma virus (HPV) typing and p53 expression with radiosensitivity in patients with cervical cancer. Methods A total of 80 patients with cervical cancer from 2014 to 2016 were enrolled, and among these patients, 40 had stage ⅠB+ⅡA disease and 40 had stage ⅡB+ⅢA disease. HPV genotype was identified and p53 expression was measured. All the patients underwent external and internal pelvic irradiation alone, and the correlation between short-term therapeutic effect and HPV typing/p53 expression was analyzed. The chi-square test or the Fisher's exact test was used for statistical analysis, and Spearman rank correlation analysis was also performed. Results The radiotherapy-insensitive (stable disease+progressive disease) group had higher p53 positive rates than the radiotherapy-sensitive (complete response+partial response) group (stage ⅠB+Ⅱ:100% vs. 80.0%, P=0.044;stage ⅡB+ⅢA:100% vs. 90.0%, P=0.013). The expression of p53 was negatively correlated with radiosensitivity (r=-0.427, P=0.000). In the radiotherapy-insensitive group of patients with stage ⅠB+Ⅱ and ⅡB+ⅢA, the rate of HPV multiple infections was higher than that of single subtype infection (65.0%/95.0% vs. 35.0%/5.0%, P=0.004 and 0.003), while in the radiotherapy-sensitive group, the rate of single subtype infection was higher than that of multiple infections (85.0%/60.0% vs. 15.0%/40.0%, P=0.004 and 0.003). The highest detection rate of HPV16 was 66.3% in all patients, and the highest detection rate of HPV18 was 60.0% in the radiotherapy-insensitive group. Conclusions High expression of p53 is associated with radioresistance in patients with cervical cancer. Patients with HPV multiple infections have poor radiosensitivity, and HPV16 is the most common subtype in dual infection. Among patients who do not achieve remission after radiotherapy, HPV multiple infections with HPV18 as the main pathogen has the highest detection rate.
Tong Tingting,Dong Lijie,Wang Li. Impact of HPV typing and p53 expression on radiosensitivity in patients with cervical cancer[J]. Chinese Journal of Radiation Oncology, 2017, 26(4): 448-452.
[1] Jemal A,Bray F,Center MM,et al. Global cancer statistics[J].CA Cancer J Clin,2011,61(2):69-90.DOI:10.3322/caac.20107 [2] Klotz LH,Herr HW,Morse MJ,et al. Intermittent endocrine therapy for advanced prostate cancer[J].Cancer,1986,58(11):2546-2550.DOI:10.1002/1097-0142(19861201)58:11<2546::AID-CNCR2820581131>3.0.CO;2-N [3] Ryu HS,Chang KH,Yang HW,et al. High cyclooxygenase-2 expression in stage ⅠB cervical cancer with lymph node metastasis or parametrial invasion[J].Gynecol Oncol,2000,76(3):320-325.DOI:10.1006/gyno.1999.5690 [4] Beskow C,Kanter L,Holgersson A,et al. Expression of DNA damage response proteins and complete remission after radiotherapy of stage ⅠB-ⅡA of cervical cancer[J].Br J Cancer,2006,94(11):1683-1689.DOI:10.1038/sj.bjc.6603153 [5] Mukherjee G,Freeman A,Moore R,et al. Biologic factors and response to radiotherapy in carcinoma of the cervix[J].Int J Gynecol Cancer,2001,11(3):187-193.DOI:10.1046/j.1525-1438.2001.01014.x [6] Shintani S,Mihara M,Li CN,et al. Up-regulation of DNA-dependent protein kinase correlates with radiation resistance in oral squamous cell carcinoma[J].Cancer Sci,2003,94(10):894-900.DOI:10.1111/j.1349-7006.2003.tb01372.x [7] Suzuki Y,Nakano T,Kato S,et al. Immunohistochemical study of cell cycle-associated proteins in adenocarcinoma of the uterine cervix treated with radiotherapy alone:p53 status has a strong impact on prognosis[J].Int J Radiat Oncol Biol Phys,2004,60(1):231-236.DOI:10.1016/j.ijrobp.2004.02.032 [8] Sun CA,Lai HC,Chang CC,et al. The significance of human papillomavirus viral load in prediction of histologic severity and size of squamous intraepithelial lesions of uterine cervix[J].Gynecol Oncol,2001,83(1):95-99.DOI:10.1006/gyno.2001.6336 [9] Halec G,Holzinger D,Schmitt M,et al. Biological evidence for a causal role of HPV16 in a small fraction of laryngeal squamous cell carcinoma[J].Br J Cancer,2013,109(1):172-183.DOI:10.1038/bjc.2013.296. [10] Holloway A,Storey A.A conserved C-terminal sequence of high-risk cutaneous beta-human papillomavirus E6 proteins alters localization and signalling of β1-integrin to promote cell migration[J].J Gen Virol,2014,95(1):123-134.DOI:10.1099/vir.0.057695-0. [11] Valente LJ,Gray DHD,Michalak EM,et al.p53 efficiently suppresses tumor development in the complete absence of its cell-cycle inhibitory and proapoptotic effectors p21,Puma,and Noxa[J].Cell Rep,2013,3(5):1339-1345.DOI:10.1016/j.celrep.2013.04.012. [12] Giambi C,Donati S,Declich S,et al. Estimated acceptance of HPV vaccination among Italian women aged 18-26 years[J].Vaccine,2011,29(46):8373-8380.DOI:10.1016/j.vaccine.2011.08.079. [13] Bouvard V,Baan R,Straif K,et al. A review of human carcinogens-part B:biological agents[J].Lancet Oncol,2009,10(4):321-322.DOI:10.1016/S1470-2045(09)70096-8. [14] Gromanov P,Zlatkov V,Ganchev G,et al. HPV prevalence and type distribution in women with normal or abnormal Pap smear in Bulgaria[J].J Med Virol,2014,86(11):1905-1910.DOI:10.1002/jmv.24020. [15] Iwasaki R,Galvez-Philpott F,Arias-Stella Jr J,et al. Prevalence of high risk human papillomavirus by cobas 4800 HPV test in urban Peru[J].Braz J Infect Dis,2014,18(5):468-472.DOI:10.1016/j.bjid.2014.01.010. [16] Clifford GM,Smith JS,Plummer M,et al. Human papillomavirus types in invasive cervical cancer worldwide:a meta-analysis[J].Br J Cancer,2003,88(1):63-73.DOI:10.1038/sj.bjc.6600688. [17] Bao YP,Li N,Smith JS,et al. Human papillomavirus type distribution in women from Asia:a meta-analysis[J].Int J Gynecol Cancer,2008,18(1):71-79. [18] Li N,Franceschi S,Howell-Jones R,et al. Human papillomavirus type distribution in 30,848 invasive cervical cancers worldwide:variation by geographical region,histological type and year of publication[J].Int J Cancer,2011,128(4):927-935.DOI:10.1002/ijc.25396. [19] Kim CJ,Jeong JK,Park M,et al. HPV oligonucleotide microarray-based detection of HPV genotypes in cervical neoplastic lesions[J].Gynecol Oncol,2003,89(2):210-217.DOI:10.1016/S0090-8258(02)00069-0. [20] Guan P,Clifford GM,Franceschi S.Human papillomavirus types in glandular lesions of the cervix:a meta-analysis of published studies[J].Int J Cancer,2013,132(1):248-250.DOI:10.1002/ijc.27663. [21] Bachtiary B,Obermair A,Dreier B,et al. Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer[J].Int J Cancer,2002,102(3):237-243.DOI:10.1002/ijc.10708. [22] 钟茜,赵霞.人乳头瘤病毒生殖道感染的流行病学与临床[J].实用妇产科杂志,2013,29(3):161-163.DOI:10.3969/j.issn.1003-6946.2013.03.001. Zhong Q,Zhao X.Epidemiology and clinical study of human papillomavirus genital tract infection[J].J Pract Obstetr Gynecol,2013,29(3):161-163.DOI:10.3969/j.issn.1003-6946.2013.03.001. [23] Munagala R,Donà MG,Rai SN,et al. Significance of multiple HPV infection in cervical cancer patients and its impact on treatment response[J].Int J Oncol,2009,34(1):263-271.DOI:10.3892/ijo_00000148. [24] Lee SA,Kang D,Seo SS,et al. Multiple HPV infection in cervical cancer screened by HPV的DNA Chip[J].Cancer Lett,2003,198(2):187-192.DOI:10.1016/S0304-3835(03)00312-4. [25] Lai CH,Chang CJ,Huang HJ,et al. Role of human papillomavirus genotype in prognosis of early-stage cervical cancer undergoing primary surgery[J].J Clin Oncol,2007,25(24):3628-3634.DOI:10.1200/jco.2007.11.2995. [26] 王媛,李莉,师晓艳.HPV分型对宫颈癌患者放疗敏感性的影响[J].医学临床研究,2014,31(9):1763-1765.DOI:10.3969/j.issn.1671-7171.2014.09.035. Wang Y,Li L,Shi XY.Impact of HPV genotypes on the sensibility of radiotherapy in patients with cervical cancer[J].J Clin Res,2014,31(9):1763-1765.DOI:10.3969/j.issn.1671-7171.2014.09.035.
2017, Vol. 26 
