Incidence,trends, and survival of oropharyngeal squamous cell cancer in Aotearoa New Zealand, 2006–2020

BackgroundAn increasing trend of oropharyngeal cancer (OPC) has been reported in several countries with different demographic characteristics, and often attributed to increases in human papillomavirus (HPV) infection. The survival of patients with OPC has steadily improved, especially for those with positive HPV status. This study assessed the incidence, trends, and survival of OPC in Aotearoa New Zealand (NZ) by age at diagnosis, sex and ethnicity.MethodsThe study included all 2109 patients resident in NZ with a primary diagnosis of oropharyngeal squamous cell carcinoma from 2006 to 2020, identified from the National Cancer Registry. We assessed age-standardised incidence rate (ASR), annual percent change (APC) and overall and relative survival rates.ResultsThe average annual incidence of OPC was 2.2 per 100,000 population. There was a steady increase of 4.9% per year over 15 years. Although the incidence rates were higher in males over the study period, the overall rate of increase was similar in males (4.9%) and in females (4.3%). The incidence was highest in the 50–69-year group (8.8/100,000 population). This age group had an incidence that increased by 7.5% per year to 2018, and then declined. The main increase in rates was seen between the birth cohort of 1946–50 and that of 1956–60. The increase in incidence was seen in Māori and Pākehā/European populations, but no increase was seen in Pacific or Asian populations. The 5-year overall relative survival rate improved from 69% in 2006‐13 to 78% in 2014–20. Survival rates were lower in older patients, females, and Māori patients.ConclusionThis study confirmed a substantial increase in OPC incidence in NZ, with some evidence to suggest a recent slowing in this increase. Māori and Pākehā/European had the highest incidence, while Pacific and Asian populations showed the lowest rates and no increase over the study period. Survival rates have improved over time, but remained lower in some demographic groups.     

湖北地区宫颈癌组织中人乳头瘤病毒16型E7基因的分离、克隆和序列分析

采用加端聚合酶链反应技术,从湖北地区一宫颈癌患者癌组织ＤＮＡ中分离出人乳头瘤病毒１６型（ＨＰＶ１６）Ｅ７基因,并在ｐＵＣ１８载体中克隆。经限制性核酸内切酶分析和ＤＮＡ序列分析,确认了含ＨＰＶ１６Ｅ７重组克隆质粒,命名ｐＨＰＶ１６Ｅ７─ＨＢ。ＤＮＡ序列分析表明,ＨＰＶ１６Ｅ７─ＨＢ基因全长２９４ｂｐ（与报道的标准株基因长度相同）,但其核苷酸顺序中有两处发生了Ｃ→Ｔ突变,即第４３位密码子ＣＡＡ变为ＴＡＡ,第７６位ＣＧＴ变为ＴＧＴ;前者使谷氨酰胺密码子变为终止密码,即无义奕变（ｎｏｎｓｅｎｓｅｍｕｔａｔｉｏｎ）。这种突变发生在２９４个碱基的ＤＮＡ扩增产物之中,不像是ＰＣＲ本身的错配,而很可能是湖北株与标准株之间的结构差异。     

金黄色葡萄球菌L型和人乳头瘤病毒与宫颈癌关系的研究

应用改良革兰氏染色和免疫组化染色（ＡＢＣ法）,对２７０例宫颈癌和３３例慢性宫颈炎进行了研究。结果发现,宫颈癌革兰氏染色切片中细菌Ｌ型感染率（７５．１％）明显高于慢性宫颈炎（４５．５％）（Ｐ＜０．０５）,金黄色葡萄球菌Ｌ型抗原阳性率（７６．２％）明显高于人乳头瘤病毒（ＨＰＶ）抗原阳性率（５７．１％）。Ｌ型、ＨＰＶ混合感染率为４２．８％。上述结果表明宫颈癌中金葡菌Ｌ型与ＨＰＶ感染均常见,尤其金葡菌Ｌ型感染更为多见;金葡菌Ｌ型与ＨＰＶ感染的致病特征相似,两者均有不同程度的空泡细胞出现。提示金葡菌Ｌ型感染可能也是宫颈癌的致癌重要因素之一。     

Tumour-infiltrating lymphocytes mediate lysis of autologous squamous cell carcinomas of the head and neck

Tumour-infiltrating lymphocytes (TIL) and tumours from six patients with squamous cell carcinomas of the head and neck (SCCHN) were investigated. The six tumours all expressed major histocompatibility complex (MHC) class I antigens both in vivo and as tumor cell lines grown in vitro. In addition, the cancer cells either overexpressed the tumour-suppressor gene product p53 or harboured human papilloma virus 16/18 (HPV). The TIL were expanded in vitro in the presence of interleukin-2, immobilised anti-CD3 mAb and soluble anti-CD28 mAb. Expanded TIL cultures contained both CD4+and CD8+T cells, but generally contained few CD56+CD3-cells of the natural killer (NK) phenotype. CD8+T cells dominated the individual TIL cultures from five of the six patients and showed significant autologous tumour cell lysis. In TIL cultures derived from four of these tumour-reactive TIL cultures, killing could be partially blocked by an anti-MHC class I mAb. TIL cultures reacting with autologous tumour cells also showed strong TCR/CD3-redirected cytotoxicity when assayed against hybridoma cells expressing anti-TCR/CD3 mAb as well as natural-killer(NK)-like activity. A number of TIL cultures devoid of autologous tumour cell lysis were capable of lysing the natural-killer(NK)-sensitive K562 cell line suggesting that the SCCHN cells themselves are resistant to NK-like lysis. In conclusion, TIL cultures from head and neck carcinomas contain T cells which, upon expansion in vitro, can lyse autologous tumour cells in a MHC-class-I-restricted fashion. Thus, the results of the present study document that carcinomas of the head and neck in some patients are infiltrated by cytotoxic T cell precursors potentially capable of rejecting the autologous tumour.     

干扰素阴道胶囊联合微波治疗宫颈炎合并高危型HPV感染对外周血Th17和Treg细胞及炎症因子的影响

目的探讨干扰素阴道胶囊联合微波治疗宫颈炎合并高危型人乳头瘤病毒(HPV)感染对外周血Th17和Treg细胞及炎症因子的影响。方法随机选择2015年1月-2018年1月在本院就诊的慢性宫颈炎合并高危型HPV感染患者90例,按随机数字表法分为观察组和对照组,每组45例。对照组给予重组人干扰素α2b栓,观察组给予重组人干扰素α2b栓联合微波治疗,治疗3个月后,观察两组患者的症状改善情况、HPV转阴率、血清炎性因子水平以及Th17和Treg细胞水平。结果观察组总有效为41例,占91.1%,对照组为73.3%,观察组显著高于对照组(P<0.05)。治疗后观察组的白带量改善率、白带脓性改善率、高危型HPV转阴率均显著高于对照组(P<0.05)。治疗前两组患者的白介素17(IL17)、肿瘤坏死因子β(TNFβ)、白介素23(IL23)水平比较,差异无统计学意义(P>0.05);治疗后两组患者的IL17、TNFβ、IL23水平均显著下降,且观察组下降更加显著(P<0.05)。治疗后观察组的Treg细胞、Th17细胞水平,Th17/Treg比值均较对照组低(P<0.05)。治疗前两组患者的滴虫、真菌、细菌性阴道炎、衣原体、解脲支原体感染人数比较差异无统计学意义(P>0.05),治疗后观察组的细菌性阴道炎、衣原体、解脲支原体感染显著降低,与对照组比较差异有统计学意义(P<0.05)。结论干扰素阴道胶囊联合微波治疗宫颈炎患者的治疗效果好,可显著改善患者症状,减轻体内炎症反应,增加HPV转阴率,调节Th17和Treg细胞,对预防宫颈癌有重要作用。     

HPV感染对阴道微生态炎症反应的影响

目的探究HPV感染与阴道微生态、炎症反应的关系。方法选取2017年11月至2018年11月在我院治疗的70例HPV感染患者(研究组),随机选取同一时期来我院进行体检的健康者70例(对照组)。治疗前后分别对研究组和对照组研究对象进行HPV检测、阴道分泌物检查以及炎症反应检查,观察并记录两组研究对象的情况。结果治疗前研究组患者HPV感染情况[高危型HPV感染31例(44.3%),低危型HPV感染为39例(55.7%)]明显高于对照组[高危型HPV感染2例(2.8%),低危型HPV感染5例(7.1%)](t=38.314 0、33.345 0,均P0.05);研究组患者阴道微生态(乳杆菌为3 000±50、厌氧菌为1 050±100、需氧菌为800±65)明显低于对照组(乳杆菌为5 114±222、厌氧菌为2 334±100、需氧菌为1 500±100)(t=15.395 1、14.521 1、16.126 0,均P0.05);研究组阴道炎症发病情况[阴道毛滴虫阴道炎29例(41.43%)、念珠菌阴道炎为22例(31.43%)、细菌性阴道炎19例(27.14%)]明显多于对照组[阴道毛滴虫阴道炎11例(15.71%)、念珠菌阴道炎9例(12.86%)、细菌性阴道炎8例(11.43%)](χ~2=11.340 0、7.002 0、5.552 0,均P0.05)。结论临床上HPV感染很常见,患者多伴发阴道炎症,HPV感染患者阴道正常菌群变少,阴道微生态环境紊乱。     

宫颈病变患者阴道微生态与高危型HPV感染及宫颈癌相关增殖基因表达的相关性

目的探讨宫颈病变患者阴道微生态与高危型HPV感染及宫颈癌相关增殖基因表达的相关性。方法选择2018年1月至2019年1月间在我院确诊为原发性宫颈癌的患者50例作为宫颈癌组,在我院诊断为宫颈糜烂的患者78例作为宫颈糜烂组,同期在我院进行体检的健康女性100例作为正常对照组。对比3组研究对象的阴道微生态失调率、高危型HPV感染率以及宫颈癌组、宫颈糜烂组患者宫颈病灶组织中宫颈癌相关增殖基因(Prdx4、Nek2、Fhit、BLCAP)mRNA表达量的差异。采用Pearson检验分析宫颈癌患者阴道微生态失调率与高危型HPV感染及宫颈癌相关增殖基因表达的相关性。结果宫颈癌组、宫颈糜烂组患者的阴道微生态失调率、高危型HPV感染率高于正常对照组,其中宫颈癌组患者这两项指标水平高于宫颈糜烂组(均P0.05)。宫颈癌组患者宫颈病灶组织中Prdx4、Nek2 mRNA表达量高于宫颈糜烂组,Fhit、BLCAP mRNA表达量低于宫颈糜烂组(均P0.05)。相关性分析发现,宫颈癌患者阴道微生态失调率与高危型HPV感染率呈正相关,与癌基因(Prdx4、Nek2)mRNA表达量呈正相关,与抑癌基因(Fhit、BLCAP)mRNA表达量呈负相关(均P0.05)。结论宫颈癌患者阴道微生态失调率较高,可能与高危型HPV感染及癌细胞增殖旺盛密切相关。     

Current Status of Human Papillomavirus-Related Head and Neck Cancer: From Viral Genome to Patient Care

Virologica Sinica - Human papillomavirus (HPV) infection identified as a definitive human carcinogen is increasingly being recognized for its role in carcinogenesis of human cancers. Up to...     

HPV DNA/RNA detection in various oral and oropharyngeal biomaterials identifies active HPV infections also in non-neoplastic tonsils

Previous studies describe a correlation between HPV-positivity and non-smoking in TSCC; p16^INK4A-expression as surrogate-marker for HPV-DNA/RNA-positivity is discussed controversially. In the present study, these parameters are assessed prospectively. HPV-status of sputum and tonsillar-swabs was analyzed to determine their validity as surrogate-marker for tissue-HPV-status.TSCC- (n = 52) and non-neoplastic tonsillar tissue (n = 163) were analyzed. HPV-DNA- and HPV-RNA-status of total sputum, cellular fraction and supernatants, tonsillar-swabs and -tissue was determined by (RT)-PCR. Immunohistochemistry determined p16^INK4A-expression.23/163 (14.2%) non-neoplastic tonsils were HPV-DNA-positive; five patients (3 HPV16, 2 HPV11) had active HPV-infections (HPV-RNA-positive), in all biomaterials. 140/163 (85.9%) patients were either HPV-DNA-positive or HPV-DNA-negative in all samples. 21/52 (40.4%) TSCC-tonsils were HPV-DNA-positive; 17 patients were HPV-RNA-positive (14 HPV16; 4 HPV18). 40/52 (76.9%) TSCC-patients were congruent in all biomaterials. p16^INK4A-expression alone would have misclassified the HPV-status of 14/52 (26.2%) TSCC-patients.This prospective study confirms the discrepancy between HPV-status and p16^INK4A-expression and the significant correlation between non-smoking and HPV-DNA-positivity. HPV-sputum- and/or swab-results do not consistently match tissue-results, possibly having (detrimental) consequences if those were used to assess tissue-HPV-status. In the 5 patients with active HPV infection in the non-neoplasitic tonsils, tonsillectomy likely prevented subsequent development of TSCC.     

Expressions of E2 and E7-HPV16 proteins in pre-malignant and malignant lesions of the uterine cervix

Continuous production of the E7 protein from different types of high risk human papilloma virus (HPV) is required for progression of malignancy. We developed antibodies against HPV type 16 E7 and E2 proteins to evaluate their utility as markers for diagnosis during early stages of cervical cancer. Forty biopsies from uterine cervices were diagnosed as low grade intraepithelial lesion (LSIL), high grade intraepithelial lesion (HSIL), squamous carcinoma (SC), in situ adenocarcinoma (ISA) and invasive adenocarcinoma (AC), all of which were infected with HPV 16. Immunohistochemistry was used to investigate the expressions of E7 and E2 (both from HPV 16) and p16. P16 was expressed in eight of 12 LSILs, in all HSILs, in 16 of 18 SC and in all ACs. E2 was expressed in six of 12 LSILs. E7 was positive in eight of 12 LSILs and in all HSIL and carcinomas. The expressions of E2 and E7 of HPV16 related to p16 expression confirmed the value of the viral oncogenic proteins as complementary to histology and support the carcinogenic model of the uterine cervix, because HPVDNA integration into cellular DNA implies the destruction of the gene encoding E2, which suppresses the expression of the E6 and E7 oncoproteins. E2 from HPV16 could be marker for LSILs, while E7 could be a marker for progression of LSILs to HSILs in patients infected by HPV16, because viral typing has little positive predictive value.