Prevalence of cervical human papillomavirus (HPV) infection in Vanuatu

To provide information on human papillomavirus (HPV) prevalence and the distribution of individual HPV types in Pacific Islands, we conducted a population-based survey in Vanuatu, South Pacific. Nine hundred and eighty-seven women between 18 and 64 years of age were included. GP5(+)/6(+)-mediated PCR assay was used for HPV testing. The prevalence of 44 HPV types was 28.4% corresponding to an age (world)-standardized prevalence of 25.0% [95% confidence interval (CI), 21.9%-28.0%]. The prevalence of high-risk (HR) HPV types was 21.7% (age-standardized prevalence of 19.2%; 95% CI, 16.4%-22.0%). Among 840 women with adequate cytologic results, 13.6% showed cervical abnormalities, including 3.6% with high-grade squamous intraepithelial lesions (HSIL) and 0.8% with invasive cervical carcinoma. HPV prevalence declined from 46.1% in women aged ≤21 to 15.3% in those ≥45 years. Being single was significantly associated with HPV positivity. HR HPV findings by PCR assay and hybrid capture 2 (HC2; conducted in Vanuatu) were moderately correlated (κ test = 0.59). The positive predictive values of HR HPV positivity for HSIL or worse were 27.6% for PCR and 35.2% for HC2 among women aged ≥30. Nearly half of screening-positive women could not be reevaluated mainly on account of the difficulty to trace back women. The availability of a rapid HPV testing method that allows see-and-treat approaches at the same visit would be, therefore, essential. On account of their high cumulative burden of cervical lesions, also women older than 40 years should be included in at least the first screening round in unscreened populations.     

Deep sequencing detects human papillomavirus (HPV) in cervical cancers negative for HPV by PCR

Background Human papillomavirus (HPV) is a necessary cause of cervical cancer, although some invasive cervical cancers may test negative by HPV PCR. We previously requested all invasive cervical cancers in Sweden during 10 years and subjected them to PCR. We also optimised methods for deep sequencing of formalin-fixed paraffin-embedded samples.Methods Using Novaseq 6000, we simultaneously sequenced total DNA and cDNA from 392 HPV PCR-negative cervical cancers. Non-human reads were queried against all known HPVs. The complete database now contains PCR and/or deep sequencing data on 2850 invasive cervical cancers.Results HPV sequences were detected in 169/392 of HPV PCR-negative cervical cancers. Overall, 30 different HPV types were detected, but only 5 types were present in proportions above 3% of cancers. More than 92% of tumours were HPV-positive in PCR and/or sequencing (95% confidence interval: 91.1–93.1%). Exploring possible reasons for failure to previously detect HPV suggest that more sensitive type-specific PCRs for HPV 31, 33, 45 and 73 targeting retained regions of HPV would have detected most of these (117/392).Conclusions Unbiased deep sequencing provides comprehensive data on HPV types in cervical cancers and appears to be an important tool for quality assurance of HPV screening.Subject terms: Infectious-disease diagnostics, Viral infection, Cervical cancer     

Telomerase, p53 and human papillomavirus infection in the uterine cervix

Human papillomavirus infection is postulated to be a major risk factor for cervical cancer, while more recent data have stressed the clinical significance of telomerase expression during tumorigenesis. This study therefore looked for any relationship between telomerase expression, presence of human papillomavirus (HPV) and expression of the high-risk HPV E6 protein at various phases of tumor progression in the uterine cervix. In addition, accumulation of the p53 protein and total tissue proliferative fraction were also studied. Telomerase was detected using a modified TRAP (telomerase repeat amplification protocol) assay. Expression of p53, Ki 67 and E6 protein was evaluated by immunocytochemistry. Presence of mutant p53 was detected using a mutant-specific ELISA. Type of HPV infection was determined by polymerase chain reaction and Southern blot using type-specific primers and probes. There was a significant correlation between the expression of telomerase with histological grade (r=0.646, p=0.00003). Fisher's exact test analysis revealed that the odds ratio of a tissue sample expressing telomerase being a case (high-grade squamous intraepithelial lesion or invasive cancer) was 28.93 (p=0.0001, 95% CI: 7.22, to 115.94). High-risk HPV-infected tissues and those expressing E6 showed increased telomerase expression (r=0.555, p=0.00001). Similarly, accumulation of p53 protein and increased cell proliferation (Ki 67 index) also correlated to the presence of telomerase (r=0.661, p=0.000004 for p53 and r=0.647, p=0.000003 for Ki 67). There was no correlation between telomerase expression and presence of p53 mutation. Activation of telomerase thus appears to be associated with high-risk-HPV infection, accumulation of inactive p53 protein and increased cell proliferation in cervical lesions.     

Oncogenic human papillomavirus (HPV) infection and uterine cervical cancer: a screening strategy in the perspective of rural India.

The predominance of cervical cancer in India can mostly be attributed to the lack of early screening. The objective of the present study has been, therefore, to determine a cost-effective oncogenic human papillomavirus (HPV)-based cervical cancer screening plan for rural Indian women. The results showed that in normal women, highest prevalence of HPV 16/18 infection was in the age group < or =23 years and lowest in > or =44 years with an insignificant change in between. HPV 16/18 infection was significantly associated with cervical erosion at age < or =23 years, but not with cytology or visual inspection with acetic acid testing at any age. The low-grade cytological lesions, however, increased only with increase in age. Fourteen per cent of the cervical malignancy was also found to be present in the age group 24-33 years with an 87% HPV infection. Here we proposed a cost-effective screening scheme in which HPV testing must be performed in women (a) < or =23 years with cervical erosion and (b) 24-43 years, as an adjunct to Pap smears (both HPV and cytology were prevalent in this group). For women > or =44 years, HPV testing might not be useful, since abnormal cytology was more prominent over the viral infection. We infer that by not performing HPV test in the group < or =23 years, approximately 76% of the high-risk HPV-infected individuals potentially "at risk" for developing cervical cancer might be missed.     

年轻女性宫颈人乳头瘤病毒感染亚型与宫颈病变的调查

目的：探讨年轻女性（年龄25~35岁）人乳头瘤病毒（HPV）感染亚型与宫颈病变的特点。方法采集1273例患者宫颈上皮细胞标本,采用PCR-反向点杂交法对其进行21种HPV分型的检测。结果1273例年轻女性患者,HPV阳性有130例,检出率为10.2%;单一型感染为115例,包括高危型感染105例,感染率为91.3%,低危型感染10例,感染率为8.7%;最常见高危型是HPV16,共35例,其次为HPV58,共17例;HPV16感染导致宫颈高级别上皮内瘤变10例,低级别上皮内瘤变11例;高危HPV阳性患者,宫颈活检证实为鳞状细胞癌的病例2例,均是HPV16感染。结论年轻女性HPV阳性检出率较高,以单一型感染和高危型感染为主,高危型HPV感染与宫颈高级别上皮内瘤变和宫颈癌的发生密切相关,其中HPV16亚型是导致年轻女性宫颈癌的主要原因。     

宫颈癌p53外显子7突变与HPV感染的关系

 目的　探讨p5 3外显子 7突变与HPV1 6、1 8型感染在宫颈癌发生中的作用及相互关系。方法　采用聚合酶链反应 (PCR)、单链构象多态性 (SSCP)、限制性酶解片段长度多态性 (RFLP)分析等方法对 49例宫颈癌组织石蜡包埋标本中p5 3外显子 7的突变与HPV1 6、1 8型感染进行了检测。结果　p5 3外显子 7的突变率 1 0 .2 0 % ,HPV DNA阳性率 87.76% ,二者差异显著 (χ2 =5 5 .90 1 ,P <0 .0 0 1 ) ,突变位点多见于密码子 2 2 9(1 /5 )、2 47(2 /5 )、2 49(1 /5 ) ;HPV1 6 DNA阳性率 87.76%显著高于HPV1 8 DNA阳性率 3 8.78%(χ2 =2 3 .2 2 7,P <0 .0 0 1 ) ;p5 3外显子 7突变与HPV感染可共存于同一标本中。结论　宫颈癌p5 3外显子7突变热点是密码子 2 2 9、2 47、2 49;少数宫颈癌是由于 p5 3外显子 7突变或 p5 3外显子 7突变与高危HPV感染相互作用所致 ,大多数宫颈癌是由于高危HPV感染尤其是HPV1 6感染所致     

Oral human papillomavirus (HPV) infection and HPV vaccination in an Australian cohort

Human papillomavirus (HPV)-related oropharyngeal cancer (OPC) is increasing in incidence, yet very little is known about oral HPV infection in the general population. In this Australian-based study we assess oral HPV prevalence according to HPV vaccination status. Participants of the Oral Diversity Study were Australian residents, aged 18 to 70 years, who filled out a questionnaire about lifestyle and sexual behaviour, and donated a saliva sample in 2020 to 2021. We obtained permission to access HPV vaccination status through record linkage with the Australian Immunisation Register. Saliva samples were DNA extracted, DNA quality checked and analysed for HPV. We recruited 1023 participants to the Oral Diversity Study. Nine hundred twenty-one returned a saliva sample for analysis, 911 passed the DNA quality check and were included in the study. The oral HPV prevalence was 7.2%, and was strongly associated with sexual behaviours. We identified 27 different HPV types; 53% of participants carried high-risk HPV types, with no difference between the vaccinated and the unvaccinated groups (53% both, P = .979). Two hundred thirty participants (26%) were HPV vaccinated. The oral prevalence of the nine HPV types included in the nonavalent HPV vaccine was significantly lower in the vaccinated participants compared to the unvaccinated (0.9% vs 3.4%; P = .022). These findings suggest that a sizeable minority of Australian residents harbour oral HPV infections, and many of these are high-risk subtypes. We found some evidence that HPV vaccination resulted in lower prevalence of oral HPV infections of vaccine-specific types. Larger surveys are required to confirm these findings.     

Relation between human papillomavirus (HPV) and cancer of uterine cervix

HPV-DNA fragments were detected in biopsy specimens (29 cases of cancer of uterine cervix, 2 cervical dysplasia and 9 normal cervix) using DNA hybridization technique. It was demonstrated that 52% of biopsy specimens of the cancer of uterine cervix was positive for HPV 16 DNA probe, while 9% was positive for HPV 18 DNA probe. 11% of non-cancerous biopsy specimens had a positive result for HPV 16 DNA probe. It was also demonstrated that the positive rate of HPV 16 DNA was 75% in grossly cauliflower and nodular type tumors but only 25% in erosion type. It seems that the positive rate of HPV 16 DNA is correlated to gross appearance of the tumor. The positive rates of HPV 16 DNA were different in 6 provinces in China. It was 64% in Shanxi Province, a high incidence area but 36% in Sichuan Province, a low incidence area. These results suggest that the carcinogenesis of cancer of the uterine cervix, be related to HPV infection.     

Looking beyond human papillomavirus (HPV) genotype 16 and 18: Defining HPV genotype distribution in cervical cancers in Australia prior to vaccination

Australia has implemented a high‐coverage HPV vaccination program but has not, to date, established the distribution of HPV types that occur in cervical cancers in Australia. This information is important for determining the potential for cervical cancer prevention with both current and broader spectrum HPV vaccines. We analysed 847 cervical cancers diagnosed 2005 to 2015 in tertiary centres in the three most populous Australian states with resolution of specimens containing multiple HPV types using laser‐capture microdissection. Archived FFPE tissue was reviewed by specialist pathologists, sandwich sectioned, and initially whole‐tissue sections genotyped for HPV. Samples were first genotyped using SPF10‐LiPA25 (version 1). Negative samples were screened with DNA ELISA kit HPV SPF10, followed by genotyping with SPF+ LiPA if ELISA positive. If still negative, samples were tested on a qPCR assay targeting the E6 region of HPV16, 18, 45 and 33. Of the 847 cancers (65.1% squamous, 28.7% adenocarcinoma, 4.3% adenosquamous, 2.0% other), 92.9% had HPV detected. Of the HPV‐positive cancers, 607 of 787 (77.1%) contained HPV16 or 18, 125 of 787 (15.9%) contained HPV31/33/45/52 or 58, and 55 (7.0%) another HPV type. There was a strong correlation between HPV type and age, with younger women most likely to have HPV16/18 detected and least likely HPV negative. Our findings indicate that cervical cancers diagnosed in Australia more frequently contain HPV16/18 than in international series. This could be due to cervical screening in Australia increasing the proportion of adenocarcinomas, in which types 18 and 16 more strongly predominate, due to prevention of squamous cancers.     

RCAS1在宫颈癌组织中的表达及其与HPV16感染的关系

背景与目的:表达在SiSo细胞上的受体结合肿瘤抗原(receptor-binding cancer antigen expressed on SiSo cells,RCAS1)在多种肿瘤组织中呈高表达,并与肿瘤逃避免疫监视有关.本研究检测RCAS1蛋白在宫颈癌组织中的表达及其与HPV16感染的相关性,并探讨其临床意义.方法:采用免疫组化SP(streptavidin-peroxidase)法,分别检测71例宫颈癌、76例宫颈上皮内瘤样病变(CIN)及20例正常宫颈上皮组织中RCAS1蛋白与HPV16 E7蛋白的表达,并分析两者的表达与临床病理因素的关系.结果:宫颈癌组织中,RCAS1蛋白主要表达于癌细胞膜和/或细胞浆,HPV16 E7蛋白主要表达于癌细胞核.正常宫颈上皮组织不表达RCAS1蛋白,CIN与宫颈癌组织中RCAS1蛋白的表达率分别为39.47%和77.46%,HPV16 E7蛋白的表达率分别为0.05%、28.94%和61.97%,提示随着宫颈病变恶性程度的进展,RCAS1与HPV16 E7表达均逐渐增强(P＜0.05).低分化宫颈癌组中RCAS1表达显著高于高、中分化宫颈癌组(P=0.002),但与患者年龄、临床分期及组织学分型无关(P＞0.05);HPV16 E7在鳞癌组中的表达显著高于腺癌组(P=0.000),但与患者年龄、临床分期、组织学分级无关(P＞0.05).RCAS1的表达与HPV16感染在宫颈癌中的表达呈正相关(r=0.780,P=0.000).结论:RCAS1基因在宫颈癌组织中表达增强,RCAS1表达强度与宫颈癌恶性程度相关;RCAS1阳性的宫颈癌组织中存在HPV16感染.     

Human papillomavirus (HPV) genotype distribution in invasive cervical cancers in France: EDITH study

Invasive cervical cancer (ICC) remains a significant cause of morbidity and mortality in France. Since human papillomavirus (HPV) is the necessary cause of ICC, the aim of this study was to assess the type-specific prevalence of HPV in ICC in France in order to locally evaluate the potential benefit of an HPV 16/18 L1 virus-like particles (VLP) vaccination. A total of 516 histological specimens collected in 15 centers were analyzed. Among them, 86% had a diagnosis of squamous cell carcinoma (SCC) whereas 14% were adenocarcinomas (ADC). HPV genotyping was performed using the INNO-LiPA assay allowing the specific detection of 24 HPV genotypes both high risk (HR) and low risk (LR). The overall HPV prevalence in ICC was 97%. The most prevalent genotypes were HPV 16 (73%) and HPV 18 (19%) followed by HPV 31 (7%), 33, 68, 45, 52 and 58 (4.1-2.3%). HPV 16 and/or 18 were associated with 82% of ICC, 10% being HPV 16 and 18 coinfections. While HPV 16 was the most prevalent type in both SCC (74%) and ADC (64%), HPV 18 was by far more prevalent in ADC (37%) compared to SCC (16%; p < 0.001). Multiple infections with at least two different HR HPV genotypes were observed in 22% of ICC. Given the high HPV 16/18 prevalence and taking into account possible production of crossneutralizing antibodies against other HPV types, HPV 16/18 L1 VLP vaccination would be expected to significantly reduce the burden of ICC in France.     

Telomerase activity and human papillomavirus in malignant, premalignant and benign cervical lesions.

The purpose of this study was to define a correlation between telomerase activity and human papillomavirus (HPV) in normal control tissue and in benign, premalignant and malignant cervical lesions. Telomerase activity was detectable in 33 out of 34 cases of squamous-cell carcinoma, five out of six cases of microinvasive carcinoma, 8 out of 20 cases and two out of six cases of high- and low-grade squamous intraepithelial lesions (SILs) respectively. The higher frequency of positive telomerase in invasive carcinoma compared with SILs was observed in both HPV-associated and non-associated groups. Whereas 92.6% of HPV-positive and 100% of HPV-negative invasive lesions expressed telomerase, only 50% of HPV-positive and 25% of HPV-negative SILs did. Interestingly, telomerase activity was also detectable in 13 out of 28 cases of benign lesions regardless of the presence of HPV. In conclusion, there may be two roles of telomerase in the cervix. The first one would present in benign lesions; the second is associated with cancer development and activated during the late stage of multistep carcinogenesis in both HPV-positive and -negative groups.     

Human papillomavirus (HPV) infection, HIV infection and cervical cancer in Tanzania, east Africa.

The presence of HPV-DNA was determined in tumor biopsies of cervical-cancer patients and in cervical swabs of non-cancer patients from Tanzania, East Africa, by Southern blot hybridization and/or PCR. HPV types 16 and 18 were detected in 38% and 32%, respectively, of 50 cervical-carcinoma biopsies. A consensus primer PCR capable of detecting a broad spectrum of HPV types revealed the presence of HPV-DNA in 59% of 359 cervical swabs of non-cancer patients. Type-specific PCR showed that types 16 and 18 accounted for 13.2% and 17.5%, respectively, of all HPV infections. Therefore we concluded that HPV 18 is more prevalent in Tanzania than in any other geographical location so far reported. The strongest risk factors for the presence of any HPV-DNA in the 359 female non-cancer patients were young age and HIV infection. The epidemiology of HPV types 16 and 18 was found to differ from that of other HPV types, being associated in univariate analysis with trichomonas vaginalis infection, martial status (single/divorced), age at first intercourse, and young age at menarche. However, young age at menarche accounted for most of the effects of all other, variables in multivariate analysis. Of the non-cancer patients, 12.8% had antibodies against HIV I (no patient being severely symptomatic), and HIV infection was highly correlated with the presence of HPV-DNA, especially types 16 and 18. While HPV-DNA of any type was detectable 1.4-fold more often in HIV-positive patients than in HIV-negative patients, evidence of an infection with HPV types 16 or 18 was found 2.2-fold more often in the HIV-positive patients. The HIV-positive women did not show an increased rate of cervical cytological abnormalities as assessed by PAP staining of a single cervical smear, the overall rate of abnormalities being 2.8%. Furthermore, the age-adjusted prevalence of HIV antibodies was found to be considerably lower in 270 cervical-carcinoma patients (3% HIV-positive) in comparison with non-cancer patients. Thus there was no association observable between the prevalence of HIV infections and the frequency of cervical cytological abnormalities or cervical cancer in the setting of this cross-sectional study.     

Invader human papillomavirus (HPV) type 16 and 18 assays as adjuncts to HPV screening of cervical papanicolaou smears with atypical squamous cells of undetermined significance

BACKGROUND:

High‐risk (HR) human papillomavirus (HPV) testing is standard practice for triaging women who have Papanicolaou (Pap) smears with atypical squamous cells of undetermined significance (ASC‐US), however, only 5% to 17% of these women have underlying cervical intraepithelial neoplasia 2 (CIN‐2)/CIN‐3. Recent reports have demonstrated that the presence of either HPV type 16 (HPV‐16) or HPV‐18 confers an elevated risk for CIN‐2/CIN‐3. The current study was designed to determine the prevalence of HPV‐16 and HPV‐18 in ASC‐US Pap smears and to determine whether further typing would enhance the risk stratification of patients for CIN‐2/CIN‐3.

METHODS:

One hundred seventy‐eight Pap smears with ASC‐US were screened retrospectively for HR HPV by using the proprietary Invader screening assay followed by typing for HPV‐16 and HPV‐18 by using Invader type‐specific probes on 100 of the samples. Clinical follow‐up results were correlated with HPV types.

RESULTS:

Fifty‐one percent of the ASC‐US samples were positive for HR HPV, the majority of which (70%) harbored non‐HPV‐16/HPV‐18 HR HPV types; 27% were associated with HPV‐16, whereas only 3% contained HPV‐18. The screening assay indicated that 46% of women who had Pap smears with ASC‐US were in need of further HPV‐16/HPV‐18 typing. Testing for HPV‐16 stratified women with ASC‐US into 3 groups: 1) 14% of women were positive for HPV‐16 and had a high risk (54%) of CIN‐2/CIN‐3 on follow‐up biopsy, 2) 35% of women were positive for non‐HPV‐16 HPV types and had an intermediate risk (9%), and 3) 51% of women were negative for HPV and had a negligible risk for CIN‐2/CIN‐3.

CONCLUSIONS:

The combined application of a proprietary screening assay and a type‐specific HPV‐16 assay demonstrated global potential for the development of tailored management protocols for women who have Pap smears with ASC‐US. Cancer 2009. © 2009 American Cancer Society.     

Trichomonas vaginalis (TV) and human papillomavirus (HPV) infection and the incidence of cervical intraepithelial neoplasia (CIN) grade III

The temporal relationship between cervical infection with Trichomonas vaginalis (TV) or human papillomavirus (HPV) and the incidence rate of cervical intraepithelial neoplasia grade three (CIN III) was examined in a cohort of 43,016 Norwegian women. From 1980 to 1989, a cervico-vaginal infection from TV and HPV was diagnosed cytologically in 988 and 678 women, respectively. During the 181,240 person-years of observation, 440 cases of CIN III/cervical cancer developed. The age-adjusted incidence rates (IR) of CIN III were 225 per 100,000 person-years among women with no cytologic evidence of infection,459 among women with TV infection, and 729 among women with HPV infection. A multiple regression model yielded a relative rate (RR) of CIN III of 2.1 (95 percent confidence interval [CI]=1.3–3.4) among women with TV infection and 3.5 (CI=1.9–6.6) among women with HPV infection, compared with women with neither infection. As CIN can be misclassified as HPV infection, the entry Pap-smears of 10 women with HPV infection who later developed CIN III were re-examined. Excluding the four discordant cases with the corresponding person-years decreased the RR of CIN III to 2.1 (CI=0.9–4.8). Our report demonstrates the limitations of studies that rely only on cytologic detection of HPV infection. Nevertheless, the results support the hypothesis that HPV is a causal factor for CIN III lesions, and also display an association between TV infection and cervical neoplasia.Dr Gram is a research fellow of the Norwegian Cancer Society. This study was supported in part by a grant from the Aakre Foundation for the fighting of cancer and a grant from the University of Tromsö. A summary of this paper was presented at the American Public Health Association Annual Meeting, Atlanta, GA, USA, 10–14 November 1991.     

Relationship between human papillomavirus and oncogenes (c-myc, N-myc) amplification in human cervical cancers

The human papillomavirus detection and oncogenes amplifications were studied on DNAs from fifteen cervical cancers. We detected HPV16 and HPV18 using Southern blot hybridization and polymerase chain reaction (PCR) technique. The positive subjects of HPVs were eight cases (53%) observed by Southern blot hybridization and fourteen cases (93%) by PCR technique. The gene amplifications of oncogenes (c-myc and N-myc) were analysed by slot-blot method and were observed in c-myc but not in N-myc. The "LARGE" gene amplification (more than five fold) in c-myc was observed in one case (7%) and the "SMALL" gene amplifications (less than five fold) were observed in six cases (40%) in human cervical cancers. Although one of five cases (20%) with HPV16 was present c-myc gene amplification, all of three cases (100%) with HPV18 were found c-myc gene amplifications. In two out of three cases obtained more than three fold c-myc gene amplifications, HPV were not detectable. It is suggested that the negative correlation between gene amplification and numbers of HPV copies exist in advanced cervical cancers.     

中国女性人乳头瘤病毒感染状况及高危型别分布的Meta分析

目的分析人乳头瘤病毒(human papillomavirus,HPV)在我国不同地区妇女中的感染情况及高危型别分布,以期为制定有效的地区宫颈癌防治策略及HPV疫苗的研制提供科学的基础数据。方法通过检索查询文献,综合分析并评价2011年7月前在国内发表的有关HPV在宫颈组织中感染及高危型别分布的相关研究。结果 HPV在我国普通女性中的感染率为15.71%,低于宫颈病变患者(15.71%vs82.43%,P0.05)。北方地区高危型HPV的平均感染率高于南方(41.57%vs14.81%,P0.05),少数民族自治区高危型HPV的平均感染率高于其他省市(56.36%vs 17.11%,P0.05)。全国范围内前6位常见高危型HPV分布依次为:HPV-16、HPV-52、HPV-58、HPV-33、HPV-18、HPV-31型。HPV-16型是我国最为常见的感染型别,其他型别在不同地区及人群中的分布有一定差异。结论 HPV的感染率及高危型别分布在我国不同地区及不同人群中有一定差异,HPV-16、HPV-52和HPV-58型是中国特有的优势感染型别。