Etiologic role of human papillomavirus infection in bladder carcinoma

BACKGROUND:

The authors elucidated an etiologic role of human papillomavirus (HPV) infection in carcinoma of the bladder.

METHODS:

One hundred seventeen of 224 patients with bladder carcinoma who were treated between 1997 and 2009 were enrolled in this study. The presence of HPV DNA was tested on frozen carcinoma tissues that were obtained by transurethral resection using a polymerases chain reaction‐based method. Localization of HPV was observed on archival tissue specimens by in situ hybridization (ISH) for high‐risk HPV DNA. Cyclin‐dependent kinase (CDK) inhibitor 2A (inhibits CDK4) (p16‐INK4a) and minichromosome maintenance protein‐7 (mcm‐7)—surrogate markers for high‐risk HPV‐E7 oncoprotein—and HPV‐L1 (capsid) protein expression were evaluated by immunohistochemistry.

RESULTS:

HPV types 16, 18, 31, 33, 52, and 58, and an unknown HPV type were detected in 18 of 117 samples (15%) from patients with bladder carcinoma. HPV16 was identified in 6 samples, HPV18 was identified in 4 samples, and HPV33 was identified in 3 samples. All were single HPV type infections. HPV was detected in 38% (12 of 28) of histologic grade 1 bladder carcinomas, 8.5% (6 of 71) of grade 2 bladder carcinomas, and in 0% (0 of 18) of grade 3 bladder carcinomas. Multivariate analysis indicated that younger age (<60 years; odds ratio [OR], 10.9; 95% confidence interval [CI], 2.6‐45.3) and grade 1 tumors (OR, 4.5; 95% CI, 1.2‐17.0) were associated with HPV infection. ISH analysis indicated that high‐risk HPV DNA was localized in the nuclei of tumor cells of all HPV‐positive samples. p16‐INK4a and mcm‐7 were expressed in 94% and 89% of HPV‐positive carcinoma cells, respectively. HPV‐L1 protein expression, which suggested reproductive HPV infection, was not observed in any carcinoma.

CONCLUSIONS:

The current results indicated that high‐risk HPV is likely to be a causative agent of some low‐grade bladder carcinomas that develop in younger patients. Cancer 2011. © 2010 American Cancer Society.     

人乳头瘤病毒检测阴性子宫颈癌的研究进展

子宫颈癌是妇科最常见的恶性肿瘤,研究证实99.7%的宫颈癌是因感染人乳头瘤病毒（human papillomavirus,HPV）造成的,但几乎所有的研究中都发现有HPV检测阴性的子宫颈癌存在。HPV检测阴性的子宫颈癌可以概括为假阴性和真阴性两种情况,造成假阴性的原因有病变小、取材有限、病毒载量低、非高危人乳头瘤病毒基因型、技术错误或检测灵敏度不足等。现有的筛查方式具有一定局限性,一些具有高灵敏度和特异性的新型分子标记物如微小核糖核酸、FAM19A4基因甲基化等已被证明有望作为子宫颈癌早期检测和诊断的指标。近年来关于HPV阴性子宫颈癌的研究越来越多,但对HPV阴性子宫颈癌患者临床特点的分析存在差异。本文主要对HPV阴性子宫颈癌假阴性的原因、筛查诊断及临床特点方面进行综述。     

Human papillomavirus infection as a risk factor for anal and perianal skin cancer in a prospective study

Human papillomavirus has emerged as the leading infectious cause of cervical and other anogenital cancers. We have studied the relation between human papillomavirus infection and the subsequent risk of anal and perianal skin cancer. A case-cohort study within two large Nordic serum banks to which about 760 000 individuals had donated serum samples was performed. Subjects who developed anal and perianal skin cancer during follow up (median time of 10 years) were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Twenty-eight cases and 1500 controls were analysed for the presence of IgG antibodies to HPV 16, 18, 33 or 73, and odds ratios of developing anal and perianal skin cancer were calculated. There was an increased risk of developing anal and perianal skin cancer among subjects seropositive for HPV 16 (OR=3.0; 95%CI=1.1-8.2) and HPV 18 (OR=4.4; 95%CI=1.1-17). The highest risks were seen for HPV 16 seropositive patients above the age of 45 years at serum sampling and for patients with a lag time of less than 10 years. This study provides prospective epidemiological evidence of an association between infection with HPV 16 and 18 and anal and perianal skin cancer.     

Differences in the risk of cervical cancer and human papillomavirus infection by education level

Background:

Cervical cancer risk is associated with low education even in an unscreened population, but it is not clear whether human papillomavirus (HPV) infection follows the same pattern.

Methods:

Two large multicentric studies (case–control studies of cervical cancer and HPV prevalence survey) including nearly 20 000 women. GP5+/GP6+ PCR was used to detect HPV.

Results:

Education level was consistently associated with cervical cancer risk (odds ratio (OR) for 0 and >5 years vs 1–5 years=1.50, 95% confidence interval (CI): 1.25–1.80 and 0.69, 95% CI: 0.57–0.82, respectively, P for trend <0.0001). In contrast, no association emerged between education level and HPV infection in either of the two IARC studies. A majority of the women studied had never had a Pap smear. The association between low education level and cervical cancer was most strongly attenuated by adjustment for age at first sexual intercourse and first pregnancy. Parity and screening history (but not lifetime number of sexual partners, husband''s extramarital sexual relationships, and smoking) also seemed to be important confounding factors.

Conclusion:

The excess of cervical cancer found in women with a low socio-economic status seems, therefore, not to be explained by a concomitant excess of HPV prevalence, but rather by early events in a woman''s sexually active life that may modify the cancer-causing potential of HPV infection.     

Different human papillomavirus 16/18 infection in Chinese non-small cell lung cancer patients living in Wuhan, China

BACKGROUND: Inconsistency in the prevalence of infection by human papillomavirus (HPV) in lung cancer patients was found between different countries with racial and geographic variations. Our previous reports have indicated that a high-risk HPV 16/18 DNA was frequently detected in Chinese lung cancer patients living in Taichung, Taiwan (Cheng et al. Cancer Res. 2001;61:2799-803). Thus, we conducted this study to verify whether there was a similar HPV 16/18 infection prevalence in lung cancer patients from Wuhan, China. METHODS: To reduce the false positive HPV detection, the paraffin sections of 73 lung tumors and 34 non-cancer controls from Wuhan, China were collected for detection of the presence of HPV 16/18 DNA by in situ hybridization (ISH). RESULTS: Our results showed that the rates of HPV 16 and/or 18 infections in patients with lung tumors were significantly higher than in 34 non-cancer control subjects (26.0 versus 2.8% for HPV 16, P = 0.030; 23.3 versus 5.7% for HPV 18, P = 0.031; 27.7 versus 5.9% for HPV 16 or 18, P = 0.003) with a similar infection frequency of HPV 16 and 18 types in lung tumors. This result indicated that HPV 16/18 infection may be associated with lung cancer development in Chinese patients from Wuhan, China. Further statistical analyses revealed that HPV 16 or 18 infection was not correlated with any clinico-pathological parameter studied, including age, gender, smoking status, tumor type, tumor stage and tumor grades. Interestingly, smoking and male patients had a higher prevalence of HPV 16, although not reaching a statistical significance, compared with non-smoking and female patients, respectively (33.3% for smokers versus 20.0% non-smokers; 33.3% for male versus 17.6% for female). As compared with the HPV 16/18 infection in Taiwan, Chinese patients with lung cancer from Wuhan had a different HPV 16/18 infection prevalence. CONCLUSION: Difference in HPV 16/18 infection in lung cancer patients from Wuhan, China and Taichung, Taiwan suggests that HPV 16/18 might play a different role in lung cancer development among Chinese living in different areas.     

Recurrent urinary tract infection and risk of bladder cancer in the Nijmegen bladder cancer study

Background:

Controversy exists on whether urinary tract infection (UTI) is a risk factor for urinary bladder cancer (UBC). Here, the association is investigated using data from one of the largest bladder cancer case–control studies worldwide.

Methods:

Information on (i) history and age at onset of regular cystitis (‘regular low-UTI'') and (ii) number and age at onset of UTI treated with antibiotics (‘UTI-ab'') from 1809 UBC patients and 4370 controls was analysed. Odds ratios (ORs) and 95% confidence intervals (CI) adjusted for age, education, smoking, and use of aspirin/ibuprofen were generated, for men and women separately.

Results:

Regular low-UTI was associated with an increased UBC risk (men: OR (95% CI) 6.6 (4.2–11); women: 2.7 (2.0–3.5)), with stronger effects in muscle-invasive UBC. Statistically significant decreased risks (ORs ∼0.65) were observed for up to five UTI-ab, specifically in those who (had) smoked and experienced UTI-ab at a younger age. In women, UTI experienced after menopause was associated with a higher UBC risk, irrespective of the number of episodes.

Conclusions:

Regular cystitis is positively associated with UBC risk. In contrast, a limited number of episodes of UTI treated with antibiotics is associated with decreased UBC risk, but not in never-smokers and postmenopausal women.     

Bladder cancer and seroreactivity to BK,JC and Merkel cell polyomaviruses: The Spanish bladder cancer study

An infectious etiology for bladder cancer has long been suspected. Merkel cell virus (MCV), BKV and JCV polyomaviruses are possible causative agents but data remain scarce. Therefore, we evaluated the seroresponse to these three polyomaviruses in association with bladder cancer risk. 1,135 incident bladder cancer subjects from five Spanish regions and 982 hospital controls matched by sex, age and region were included. 99% of cases were urothelial‐cell carcinomas. Antibody response against MCV, BKV and JCV was measured by enzyme immunoassay using Virus‐Like‐Particles. Our results show a similar seroprevalence in cases and controls : 64/60% for BKV, 83/82% for MCV and 87/83% for JCV. However, among seropositive subjects, higher median seroreactivities were observed in cases compared to controls for BKV (0.84 vs. 0.70, p‐value = 0.009) and MCV (1.81 vs. 0.65, p‐value < 0.001). Increased bladder cancer risk was observed for BKV (OR = 1.4, 95%CI 1.04–1.8) and for MCV (OR = 1.5, 95%CI 1.2–1.9), when comparing highest to lowest seroreactivity tertiles. The associations of BKV and MCV with bladder cancer were independent of each other and neither smoking status nor disease stage and grade modified them. Furthermore, no association was observed between seroresponse to JCV and bladder cancer. Therefore, we conclude that BKV and MCV polyomavirus infection could be related to an increased bladder cancer risk.     

Long-term outcomes of high-risk human papillomavirus infection support a long interval of cervical cancer screening

Knowing that infection of high-risk human papillomavirus (HPV) causes virtually all cervical cancer (CC), the long-term outcomes of HPV infection, especially the absolute risk and time lapse of developing CC, are beyond the scope of ordinary follow-up study owing to ethical concerns. The present study followed the natural history and long-term outcomes of HPV infection in a cohort of women by national health insurance care and data linkage without additional disturbance. The status of cervical HPV infection was determined in 1708 healthy women, aged 20-90 (median 43), enrolled from 10 hospitals in seven cities around the island country of Taiwan. Records of consecutive Pap smear results and cancer reports of 108 cytology-negative, HPV-positive and 1202 cytology- and HPV-negative women with no prior record of CC or abnormal cervical cytology were retrospectively analysed for a duration of up to 75 months (median 61 months). The cumulative incidences of high-grade squamous intraepithelial lesion (HSIL) and in situ/invasive cancer in HPV-positive women were 5.6 and 3.7%, respectively, and those in HPV-negative women were 0.3 and 0%. After adjusting for other risk factors, HPV-positive subjects had 24.9 (95% CI: 7.0-108.3; P<0.0001) folds of risk of developing HSIL or above cervical neoplasia as compared to HPV-negative subjects, whereas risk for low-grade intraepithelial lesion and atypical squamous cytology was not increased. The study showed that women with a prevalent infection of high-risk HPV had a 4% cumulative risk for CC in 6 years, whereas those tested negative had little risk. The result supports an HPV test-orientated CC screening programme with intervals of at least 5 years.     

Association between human papillomavirus infection and prostate cancer: A global systematic review and meta‐analysis

Although an increasing number of studies have been conducted to evaluate the association between human papillomavirus (HPV) infections and distribution of HPV types worldwide with the risk of prostate cancer (PC), the results remain inadequate. Hence, we investigated the association between HPV infection and PC risk using a meta‐analysis. Relevant studies from January 1990 to December 2016 were searched in PubMed, Web of sciences, and Scopus databases. Pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were calculated to find the association between the prevalence of HPV and prostate cancer risk. To do so, data from 24 studies with 5546 prostate cancer cases were pooled in order to evaluate the heterogeneity of chief parameters including study region, specimen type, HPV DNA source, detection technique, publication calendar period, and Gleason score. All statistical analyses were performed using STATA 11 and MedCalc 13. A significant positive association was found between HPV infection and PC risk (OR = 1.281; P = 0.026). The genotype 16 was more frequently found in patients with PC which significantly increased the cancer risk (OR = 1.60; P < 0.001). Age 65 and older could significantly escalate PC risk (OR = 3.564; P < 0.001). Our results clearly favor the potential pathogenetic link between HPV infection and increased risk of PC affirming that HPV infections could play a part in the risk of PC.     

Antibodies against high‐risk human papillomavirus proteins as markers for invasive cervical cancer

Different human papillomavirus (HPV) genes are expressed during the various phases of the HPV life cycle and may elicit immune responses in the process towards malignancy. To evaluate their association with cervical cancer, antibodies against proteins from HPV16 (L1, E1, E2, E4, E6 and E7) and HPV18/31/33/35/45/52/58 (L1, E6 and E7) were measured in serum of 307 invasive cervical cancer cases and 327 controls from Algeria and India. Antibody response was evaluated using a glutathione S‐transferase‐based multiplex serology assay and HPV DNA detected from exfoliated cervical cells using a GP5+/6+‐mediated PCR assay. Among HPV16 DNA‐positive cases, seroprevalence of HPV16 antibodies ranged from 16% for HPV16 E1 to 50% for HPV16 E6 and all were significantly higher than controls. Seroprevalence of E6, E7 and L1 antibodies for HPV18 and for at least one of HPV31/33/35/45/52/58 were also higher in cases positive for DNA of the corresponding type (50% and 30% for E6 of HPV18 and HPV31/33/35/45/52/58 combined, respectively). E6 and E7 antibodies were rarely found in controls, but cross‐reactivity was evident among cancer cases positive for DNA of closely phylogenetically‐related HPV types. E6 or E7 antibodies against any of the eight HPV types were detected in 66.1% of all cervical cancer cases, as compared to 10.1% of controls. E6, and to a lesser extent E7, antibodies appear to be specific markers of HPV‐related malignancy. However, even among cases positive for the same type of HPV DNA, approximately one‐third of cervical cancer cases show no detectable immune response to either E6 or E7.     

人乳头瘤病毒感染与宫颈癌前病变和宫颈癌及其预后的关系

目的 :探讨人乳头瘤病毒 (humanpapillomavirus ,HPV)与宫颈癌前病变 (cervi calintraepithelialneoplasia ,CIN)和宫颈癌的关系以及与它们的预后关系。方法 :采用第 2代杂交捕获试验法检测我院门诊和住院患者 994例随访手术治疗患者 99例 ,随访患者同时行宫颈细胞学、阴道镜检查 ,以病理结果为金标准 ,按宫颈病变严重程度比较高危型HPV的检出率 ,以及比较术前术后宫颈癌前病变、宫颈癌感染高危型HPV变化情况。结果 :以HPVDNA≥ 1 0pg/mL为阳性标准 ,慢性宫颈炎、CIN各组及宫颈癌分别为 46 92 % ( 2 0 6/4 3 9)、65 71% ( 2 3 /3 5 )、81 82 % ( 3 6/4 4)、 98 41%( 62 /63 )、82 3 2 % ( 3 40 /4 13 )。随访患者细胞学 ,阴道镜检查除 1例CIN3患者为阳性 ,其余均为阴性 ,术后HPV持续阳性率为 2 1 18% ,其中 1例诊断为宫颈原位癌。结论 :高危型HPV感染与宫颈癌前病变和宫颈癌有明显相关性 ;宫颈锥切术后HPV持续阳性患者为复发的高危人群 ,应严密随访     

High viral loads of human papillomavirus predict risk of invasive cervical carcinoma

High loads of human papillomavirus (HPV) 16 and HPV 18/45 increase the risk of developing invasive cervical carcinoma, revealing higher risk in percentiles of highest viral loads for HPV 16 (odds ratio (OR) 58.7, 95% confidence interval (CI) 21.9-151.4) compared to HPV 18/45 (OR 3.3, 95% CI 1.5-7.2). Thus, HPV load is a type-dependent risk marker for invasive carcinoma.     

Human papillomavirus infection in women with and without cervical cancer in Tehran, Iran

No data exist on the population prevalence of, or risk factors for, human papillomavirus (HPV) infection in Iran or the Middle East. Cervical specimens were obtained from 825 married women aged 18-59 years from the general population of Tehran, Iran and from 45 locally diagnosed invasive cervical cancers (ICC) according to the standardized protocol of the International Agency for Research on Cancer HPV Prevalence Surveys. HPV was detected and genotyped using a GP5+/6+ PCR-based assay. HPV prevalence in the general population was 7.8% (95% confidence interval: 6.0-9.8) (5.1% of high-risk types), with no significant variation by age. HPV positivity was significantly higher among divorced women, women in polygamous marriages and those reporting husband's absence from home for >7 nights/month. HPV16/18 accounted for 30 and 82.2% of HPV-positive women in the general population and ICC, respectively. Cervical cancer prevention policies should take into account the relatively low HPV prevalence in this population.     

宫颈癌患者人乳头瘤病毒感染分布特点

目的:探讨人乳头瘤病毒(HPV)各亚型在广西沿海地区宫颈癌患者中的分布情况,HPV感染与宫颈癌患者的年龄、临床分期、病理类型、分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发的关系。方法:通过凯普导流杂交HPV DNA检测法,对76例宫颈癌患者宫颈脱落细胞进行21种HPV亚型的检测。结果:宫颈癌HPV总阳性率为90.8%。宫颈癌患者HPV阳性各亚型出现的频率排序为:HPV16(56.5%),HPV18、33、58各(7.2%),HPV52、53各(5.8%),HPV31(4.3%),HPV45(2.9%),HPV35、51、56、66、68各(1.4%)。HPV6(5.8%),HPV11、44、43各(1.4%)均合并在高危感染中。HPV感染与临床分期、肿瘤分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发关联无显著性(P>0.05),与年龄密切相关,鳞癌HPV阳性率明显高于腺癌及其它癌,差异有统计学意义(P<0.05)。结论:广西沿海地区妇女宫颈癌患者中以HPV16、18、33、58感染为主要型别。HPV感染与宫颈癌的临床分期、肿瘤分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发无明显相关性,与发病年龄、病理类型有关。     

Human papillomavirus infection and use of oral contraceptives

Human papillomavirus (HPV) infection is thought to be a necessary but not sufficient cause of most cases of cervical cancer. Since oral contraceptive use for long durations is associated with an increased risk of cervical cancer, it is important to know whether HPV infection is more common in oral contraceptive users. We present a systematic review of 19 epidemiological studies of the risk of genital HPV infection and oral contraceptive use. There was no evidence for a strong positive or negative association between HPV positivity and ever use or long duration use of oral contraceptives. The limited data available, the presence of heterogeneity between studies and the possibility of bias and confounding mean, however, that these results must be interpreted cautiously. Further studies are needed to confirm these findings and to investigate possible relations between oral contraceptive use and the persistence and detectability of cervical HPV infection.     

EUROGIN 2014 roadmap: Differences in human papillomavirus infection natural history,transmission and human papillomavirus‐related cancer incidence by gender and anatomic site of infection

Human papillomaviruses (HPVs) cause cancer at multiple anatomic sites in men and women, including cervical, oropharyngeal, anal, vulvar and vaginal cancers in women and oropharyngeal, anal and penile cancers in men. In this EUROGIN 2014 roadmap, differences in HPV‐related cancer and infection burden by gender and anatomic site are reviewed. The proportion of cancers attributable to HPV varies by anatomic site, with nearly 100% of cervical, 88% of anal and <50% of lower genital tract and oropharyngeal cancers attributable to HPV, depending on world region and prevalence of tobacco use. Often, mirroring cancer incidence rates, HPV prevalence and infection natural history varies by gender and anatomic site of infection. Oral HPV infection is rare and significantly differs by gender; yet, HPV‐related cancer incidence at this site is several‐fold higher than at either the anal canal or the penile epithelium. HPV seroprevalence is significantly higher among women compared to men, likely explaining the differences in age‐specific HPV prevalence and incidence patterns observed by gender. Correspondingly, among heterosexual partners, HPV transmission appears higher from women to men. More research is needed to characterize HPV natural history at each anatomic site where HPV causes cancer in men and women, information that is critical to inform the basic science of HPV natural history and the development of future infection and cancer prevention efforts.     

宫颈癌患者人乳头瘤病毒感染分布特点

目的：探讨人乳头瘤病毒（HPV）各亚型在广西沿海地区宫颈癌患者中的分布情况,HPV感染与宫颈癌患者的年龄、临床分期、病理类型、分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发的关系。方法：通过凯普导流杂交HPV DNA检测法,对76例宫颈癌患者宫颈脱落细胞进行21种HPV亚型的检测。结果：宫颈癌HPV总阳性率为90.8%。宫颈癌患者HPV阳性各亚型出现的频率排序为：HPV16（56.5%）,HPV18、33、58各（7.2%）,HPV52、53各（5.8%）,HPV31（4.3%）,HPV45（2.9%）,HPV35、51、56、66、68各（1.4%）。HPV6（5.8%）,HPV11、44、43各（1.4%）均合并在高危感染中。HPV感染与临床分期、肿瘤分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发关联无显著性（P〉0.05）,与年龄密切相关,鳞癌HPV阳性率明显高于腺癌及其它癌,差异有统计学意义（P〈0.05）。结论：广西沿海地区妇女宫颈癌患者中以HPV16、18、33、58感染为主要型别。HPV感染与宫颈癌的临床分期、肿瘤分化程度、肿瘤盆腔淋巴结转移及肿瘤的复发无明显相关性,与发病年龄、病理类型有关。     

Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer

Smoking and alcohol are well-known etiological factors in tonsillar cancer. However, as in cervical cancer, human papillomavirus (HPV) is currently found in a sizable proportion of tonsillar cancer. Recent reports from the U.S. and Finland show an increase in the incidence of tonsillar cancer, without a parallel rise in smoking and alcohol consumption. This study investigates whether the incidence of tonsillar cancer has also changed in Sweden and whether a possible explanation of the increase is a higher proportion of HPV-positive tonsillar cancer. The incidence of tonsillar cancer between 1970 and 2002 in the Stockholm area was obtained from the Swedish Cancer Registry. In parallel, 203 pretreatment paraffin-embedded tonsillar cancer biopsies taken during 1970-2002 from patients in the Stockholm area were tested for presence of HPV DNA by PCR. The incidence of tonsillar cancer increased 2.8-fold (2.6 in men and 3.5 in women) from 1970 to 2002. During the same period, a significant increase in the proportion of HPV-positive tonsillar cancer cases was observed, as it increased 2.9-fold (p < 0.001). The distribution of HPV-positive cases was 7/30 (23.3%) in the 1970s, 12/42 (29%) in the 1980s, 48/84 (57%) in the 1990s and 32/47 (68%) during 2000-2002. We have demonstrated a highly significant and parallel increase both in the incidence of tonsillar cancer and the proportion of HPV-positive tumors. Hence, HPV may play an important role for the increased incidence of tonsillar cancer. This should definitely influence future preventive strategies as well as treatment for this type of cancer.     

人乳头瘤病毒１６型感染与非小细胞肺癌的相关性研究

目的　了解人乳头瘤病毒１６型（ＨＰＶ-１６）感染与非小细胞肺癌（ＮＳＣＬＣ）发生、发展及预后的相关性。方法应用免疫组织化学技术（ＳＡＢＣ法）检测ＨＰＶ １６在４３例ＮＳＣＬＣ组织和２７例肺良性病变组织中的表达情况,结合临床病理资料和随访资料进行回顾性研究。结果　ＨＰＶ-１６在ＮＳＣＬＣ组织中阳性表达率为３９.５％（１７／４３）,高于肺良性病变的７.４％（Ｐ＜０.０１）。ＮＳＣＬＣ组织ＨＰＶ-１６表达与患者的性别、年龄、肿瘤部位、肿瘤大小、病理类型、淋巴结转移、ＴＮＭ分期、吸烟与否无关（Ｐ＞００５）。ＨＰＶ-１６阳性和阴性表达的ＮＳＣＬＣ患者的术后３年、５年生存率分别为３９.３％、３４.３％和５９.９％、４４.７％（Ｐ＞０.０５）。结论　ＨＰＶ-１６感染对ＮＳＣＬＣ的发生可能起到一定的作用。