HPV相关性和非HPV相关性口腔/口咽鳞状细胞癌的临床病理分析

doi:10.3969/j.issn.1005-4979.2023.03.004

摘要/Abstract

摘要：

目的：对我院诊断的人乳头瘤病毒（human papilloma virus, HPV）相关性和非HPV相关性口腔鳞状细胞癌（oral squamous cell carcinoma, OSCC）和口咽鳞状细胞癌（oropharyngeal squamous cell carcinoma, OPSCC）进行临床病理分析，以深入认识二者在临床和病理学上的差异性。方法：收集从2018年12月1日至2021年11月30日就诊于吉林大学口腔医院并经病理诊断为OSCC/OPSCC的病例，通过免疫组织化学染色法检测p16的表达、聚合酶链反应（polymerase chain reaction, PCR）检测HPV DNA、PCR-反向点杂交技术检测高危HPV亚型，将其分为HPV相关性鳞状细胞癌和非HPV相关性鳞状细胞癌。分别从患者的基本信息、临床特征和病理学表现等方面对二者进行统计学分析。结果：HPV相关性OSCC和非HPV相关性OSCC在浸润深度（depth of invasion, DOI）方面的差异具有统计学意义（P<0.05）；HPV相关性OPSCC和非HPV相关性OPSCC在Ki-67阳性率是否大于70%方面，差异具有统计学意义（P<0.001）。结论：在诊断时，区分HPV相关性和非HPV相关性OSCC/OPSCC能为该病治疗方案的选择提供依据，并为患者的预后提供可参考指标，能丰富HPV相关性头颈部鳞状细胞癌（head and neck squamous cell carcinoma, HNSCC）领域的临床病理资料，提高对HPV相关性OSCC/OPSCC的认知。

关键词: 高危型人乳头瘤病毒, 口腔鳞状细胞癌, 口咽鳞状细胞癌, p16

Abstract:

Objective: To make a clinicopathological analysis of human papilloma virus (HPV)-related and non-HPV-related oral/oropharyngeal squamous cell carcinoma (OSCC/OPSCC) diagnosed in our hospital, and to further understand the differences between the two diseases in clinical and pathological aspects. Methods: The cases of OSCC/OPSCC diagnosed from December 1, 2018 to November 30, 2021 in the Hospital of Stomatology, Jilin University were collected. The diagnoses of HPV-related and non-HPV-related squamous cell carcinoma were made based on the detection of p16 by immunohistochemical staining, HPV DNA by polymerase chain reaction (PCR), and high-risk HPV subtypes by PCR-reverse dot hybridization. Statistical analyses were made according to the basic information, clinical characteristics, and pathological manifestations of patients. Results: There was a significant difference in the depth of invasion (DOI) between HPV-related and non-HPV-related OSCC; there was a statistical difference between HPV-related and non-HPV-related OPSCC in terms of the Ki-67 positive rate, whether over 70% or not. Conclusion: To distinguish HPV-related and non-HPV-related OSCC/OPSCC in diagnosis so as to provide a basis for the selection of treatment options and a reference index for the prognosis of patients, and enrich the clinicopathological data in the field of HPV-related head and neck squamous carcinoma (HNSCC), thus improve the knowledge of HPV-related OSCC/OPSCC.

Key words: high-risk human papilloma virus, oral squamous cell carcinoma, oropharyngeal squamous cell carcinoma, p16

中图分类号:

R782

王晓玲, 强金彪, 曲明, 张雨晴, 乔春燕, 张泽兵, 史册. HPV相关性和非HPV相关性口腔/口咽鳞状细胞癌的临床病理分析[J]. 《口腔颌面外科杂志》, 2023, 33(3): 155-163.

WANG Xiaoling, QIANG Jinbiao, QU Ming, ZHANG Yuqing, QIAO Chunyan, ZHANG Zebing, SHI Ce. Clinicopathological analysis of HPV-related and non-HPV-related oral/oropharyngeal squamous cell carcinoma[J]. 《Journal of Oral and Maxillofacial Surgery》, 2023, 33(3): 155-163.

https://journal06.magtech.org.cn/Jweb_joms/CN/Y2023/V33/I3/155

图/表 9

参考文献 39

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引物名称	引物序列（5'-3'）	扩增长度/bp
广谱引物1: CPI/Ⅱ		188
正向: CPI	TTA TCW TAT GCC CAY TGT ACC AT
反向: CPII	ATG TTA ATW SAG CCW CCA AAA TT
广谱引物2: GP5⁺/6⁺		150
正向: GP5⁺	TTT GTT ACT GTG GTA GAT ACT AC
反向: GP6⁺	GAA AAA TAA ACT GTA AAT CAT ATT C
广谱引物3: MY09/11		450
正向: MY11	GCM CAG GGW CAT AAY AAT GG
反向: MY09	CGT CCM ARR GGA WAC TGA TC

引物名称	引物序列（5'-3'）	扩增长度/bp
广谱引物1: CPI/Ⅱ		188
正向: CPI	TTA TCW TAT GCC CAY TGT ACC AT
反向: CPII	ATG TTA ATW SAG CCW CCA AAA TT
广谱引物2: GP5⁺/6⁺		150
正向: GP5⁺	TTT GTT ACT GTG GTA GAT ACT AC
反向: GP6⁺	GAA AAA TAA ACT GTA AAT CAT ATT C
广谱引物3: MY09/11		450
正向: MY11	GCM CAG GGW CAT AAY AAT GG
反向: MY09	CGT CCM ARR GGA WAC TGA TC

基本信息	HPV相关性[n(%)]	非HPV相关性[n(%)]	合计/例	比例	P值	基本信息	HPV相关性[n(%)]	非HPV相关性[n(%)]	合计/例	比例	P值
性别					0.47	蒙古族	0	8(100)	8	0∶8.0
男	8(5.52)	137(94.48)	145	1∶17.1		满族	0	3(100)	3	0∶3.0
女	6(8.00)	69(92.00)	75	1∶11.5		外国血统	0	1(100)	1	0∶1.0
发病年龄/岁						居住地					0.35
平均值±标准差	61.00±9.36	59.02±10.30			0.49	城市	10(7.63)	121(92.37)	131	1∶12.1
中位数	62.5(46~72)	59.0(26~83)				农村	4(4.49)	85(95.51)	89	1∶21.3
(最小值~最大值)						婚姻状况					0.37
20~29	0	3(100)	3	0∶3.0	0.07	已婚	13(6.37)	191(93.63)	204	1∶14.7
30~39	0	6(100)	6	0∶6.0		离婚	0	9(100)	9	0∶9.0
40~49	4(18.18)	18(81.82)	22	1∶4.5		丧偶	1(25.00)	3(75.00)	4	1∶3.0
50~59	1(1.20)	82(98.80)	83	1∶82.0		未婚	0	3(100)	3	0∶3.0
60~69	5(6.94)	67(93.06)	72	1∶13.4		血型					0.52
70~79	4(12.50)	28(87.50)	32	1∶7.0		A	2(3.23)	60(96.77)	62	1∶30.0
80~89	0	2(100)	2	0∶2.0		B	5(7.04)	66(92.96)	71	1∶13.2
民族					0.80	AB	3(11.54)	23(88.46)	26	1∶7.7
汉族	14(7.07)	184(92.93)	198	1∶13.1		O	4(6.56)	57(93.44)	61	1∶14.3
朝鲜族	0	10(100)	10	0∶10.0		总计	14(6.36)	206(93.64)	220	1∶14.7

基本信息	HPV相关性[n(%)]	非HPV相关性[n(%)]	合计/例	比例	P值	基本信息	HPV相关性[n(%)]	非HPV相关性[n(%)]	合计/例	比例	P值
性别					0.47	蒙古族	0	8(100)	8	0∶8.0
男	8(5.52)	137(94.48)	145	1∶17.1		满族	0	3(100)	3	0∶3.0
女	6(8.00)	69(92.00)	75	1∶11.5		外国血统	0	1(100)	1	0∶1.0
发病年龄/岁						居住地					0.35
平均值±标准差	61.00±9.36	59.02±10.30			0.49	城市	10(7.63)	121(92.37)	131	1∶12.1
中位数	62.5(46~72)	59.0(26~83)				农村	4(4.49)	85(95.51)	89	1∶21.3
(最小值~最大值)						婚姻状况					0.37
20~29	0	3(100)	3	0∶3.0	0.07	已婚	13(6.37)	191(93.63)	204	1∶14.7
30~39	0	6(100)	6	0∶6.0		离婚	0	9(100)	9	0∶9.0
40~49	4(18.18)	18(81.82)	22	1∶4.5		丧偶	1(25.00)	3(75.00)	4	1∶3.0
50~59	1(1.20)	82(98.80)	83	1∶82.0		未婚	0	3(100)	3	0∶3.0
60~69	5(6.94)	67(93.06)	72	1∶13.4		血型					0.52
70~79	4(12.50)	28(87.50)	32	1∶7.0		A	2(3.23)	60(96.77)	62	1∶30.0
80~89	0	2(100)	2	0∶2.0		B	5(7.04)	66(92.96)	71	1∶13.2
民族					0.80	AB	3(11.54)	23(88.46)	26	1∶7.7
汉族	14(7.07)	184(92.93)	198	1∶13.1		O	4(6.56)	57(93.44)	61	1∶14.3
朝鲜族	0	10(100)	10	0∶10.0		总计	14(6.36)	206(93.64)	220	1∶14.7

临床情况	HPV相关性[n(%)]	非HPV相关性[n(%)]	合计/例	比例	P值
病史时长(t)/月					0.58
0<t≤6	10(5.62)	168(94.38)	178	1∶16.8
6<t≤12	3(12.50)	21(87.50)	24	1∶7.0
12<t≤24	1(12.50)	7(87.50)	8	1∶7.0
24<t≤36	0	6(100)	6	0∶6.0
t>36	0	4(100)	4	0∶4.0
首发/复发					0.70
首发	13(6.22)	196(93.78)	209	1∶15.1
复发	1(9.09)	10(90.91)	11	1∶10.0
发病部位					0.84
舌前2/3	7(8.43)	76(91.57)	83	1∶10.9
唇黏膜	0	15(100)	15	0∶15.0
颊黏膜	2(9.52)	19(90.48)	21	1∶9.5
口底	3(6.67)	42(93.33)	45	1∶14.0
牙龈	2(3.77)	51(96.23)	53	1∶25.5
硬腭	0	2(100)	2	0∶2.0
磨牙后区	0	1(100)	1	0∶1.0
自觉症状					0.97
无明显症状	2(7.14)	26(92.86)	28	1∶13.0
疼痛	11(6.32)	163(93.68)	174	1∶14.8
舌体运动受限	0	15(100)	15	0∶15.0
破溃出血	1(7.14)	13(92.86)	14	1∶13.0
麻木	0	5(100)	5	0∶5.0
不适	0	3(100)	3	0∶3.0
张口受限	0	1(100)	1	0∶1.0
发音不清	0	1(100)	1	0∶1.0
不良嗜好
吸烟	7(5.60)	118(94.40)	125	1∶16.9	0.59
不吸烟	7(7.37)	88(92.63)	95	1∶12.6
饮酒	5(5.56)	85(94.44)	90	1∶17.0	0.68
不饮酒	9(6.92)	121(93.08)	130	1∶13.4
只吸烟	2(4.76)	40(95.24)	42	1∶20.0	0.79
只饮酒	0	7(100)	7	0∶7.0
吸烟、饮酒	5(6.02)	78(93.98)	83	1∶15.6
不吸烟、不喝酒	7(7.95)	81(92.05)	88	1∶11.6
系统病史					0.69
健康	10(7.58)	122(92.42)	132	1∶12.2
心脑血管疾病	2(2.90)	67(97.10)	69	1∶33.5
糖尿病	3(15.79)	16(84.21)	19	1∶5.3
消化系统疾病	0	5(100)	5	0∶5.0
癌症后	0	3(100)	3	0∶3.0
肺部疾病	0	4(100)	4	0∶4.0
肾脏疾病	0	2(100)	2	0∶2.0
血液疾病	0	1(100)	1	0∶1.0
其他	0	1(100)	1	0∶1.0
肿物形态					0.70
浸润型	7(8.05)	80(91.95)	87	1∶11.4
外生型	3(4.92)	58(95.08)	61	1∶19.3
溃疡型	4(5.56)	68(94.44)	72	1∶17.0
T分期					0.22
T1	5(13.89)	31(86.11)	36	1∶6.2
T2	4(4.30)	89(95.70)	93	1∶22.3
T3	3(6.67)	42(93.33)	45	1∶14.0
T4	2(4.35)	44(95.65)	46	1∶22.0
总计	14(6.36)	206(93.64)	220	1∶14.7

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