Correlation of human papillomavirus 16 and 18 with cervical neoplasia in histological typing and clinical stage in Taiwan: an in-situ polymerase chain reaction approach

BACKGROUND AND OBJECTIVES: In situ polymerase chain reaction (ISPCR) promises to considerably enhance our ability to detect a few copies of target nucleic acid sequences in fixed tissues and cells. The aim of this study was to investigate cervical carcinoma to determine the human papillomavirus (HPV) types on paraffin-embedded tissue sections by ISPCR and standard in situ hybridization. The results will correlate the morphological characteristics of lesions with viral typing results. METHODS: This study examined prevalence of HPV 16 and 18 DNA in biopsies from 85 cervical cancer patients by ISPCR, employing HPV 16, 18 consensus primers. There are 45 patients with squamous cell carcinomas, 13 with adenocarcinoma, 2 with adenosquamous carcinomas, 3 with small cell carcinomas, and 22 carcinoma in situ. The relation between the types of HPV detected, tumor type, and clinical stage were analyzed. RESULTS: Fifty-two of 85 biopsies were HPV 16- or 18-positive, HPV 16 being the most prevalent type. Squamous cell carcinoma had a high prevalence of HPV 16 and adenocarcinoma had a high prevalence of HPV 18. HPV 18 was the predominant type among high clinical stage (III-IV) cases while HPV 16 and mixed HPV 16 with HPV18 were significantly correlated with low clinical stage (0-I-II). CONCLUSION: Our results indicate that certain malignant cervical tumor phenotypes and stages correlate with specific HPV type, and that ISPCR is a sensitive and fast method to detect HPV in these patients.     

Incidence and prognostic impact of high-risk HPV tumor infection in cervical esophageal carcinoma

Background

Cervical esophageal carcinoma (CEC) is an uncommon malignancy. Limited data supports the use of definitive chemoradiotherapy (CRT) as primary treatment. Furthermore, the role of human papillomavirus (HPV) tumor infection in CEC remains unknown. This study retrospectively analyzes both outcomes of CEC patients treated with CRT and the incidence and potential role of HPV tumor infection in CEC lesions.

Methods

A total of 37 CEC patients were treated with definitive CRT at our institution between 1987 and 2013. Of these, 19 had tumor samples available for high-risk HPV (types 16 and 18) pathological analysis.

Results

For all patients (n=37), 5-year overall survival (OS), disease-free survival (DFS), and loco-regional control (LRC) rates were 34.1%, 40.2%, and 65.6%, respectively. On pathological analysis, 1/19 (5.3%) patients had an HPV-positive lesion.

Conclusions

Definitive CRT provides disease-related outcomes comparable to surgery. Moreover, HPV tumor infection in CEC is uncommon and its prognostic role is unclear. Our data contribute to the construction of an anatomical map of HPV tumor infection in squamous cell carcinomas (SCC) of the upper aerodigestive tract, and suggest a steep drop in viral infection rates at sites distal to the oropharynx, including the cervical esophagus.     

The predicted impact of vaccination on human papillomavirus infections in Australia

Vaccines based on human papillomavirus (HPV) 16 and 18 virus-like particles have the potential to prevent approximately 70% of cervical cancers. In Australia, public vaccination against HPV commenced in April 2007, and includes routine vaccination of females aged 12-13 years, and a 2-year school and GP-based catch-up in females aged 12-26 years. The objectives of this study were to estimate initial vaccination coverage rates, to describe current patterns of sexual behavior in young females, and to predict the impact of vaccination on HPV16 infections. We reviewed early coverage data, estimating that coverage in 2007/2008 will reach 86% (feasible range 67-90%) for 12- to 13-year-old girls, with lower rates attained in older females. A review of survey data found that the median age of first intercourse in Australian females is 16 years, with approximately 90% of women sexually active at 22 years. Using these data, we performed an analysis of HPV transmission to predict the impact of vaccination on HPV infection rates. The public program is predicted to result in a reduction in the age-standardized incidence of HPV16 infections of 56% by 2010 (feasible range 48-61%), and 92% by 2050 (feasible range 76-95%). Elective vaccination of older women and vaccination of males may provide some incremental gains, but the benefits to women of vaccinating males will be less if coverage of females remains high. In conclusion, the current vaccination program is expected to result in a substantial and rapid reduction in the incidence of HPV16 in Australia.     

Human papillomavirus vaccination 2020 guideline update: American Cancer Society guideline adaptation

The American Cancer Society (ACS) presents an adaptation of the current Advisory Committee on Immunization Practices recommendations for human papillomavirus (HPV) vaccination. The ACS recommends routine HPV vaccination between ages 9 and 12 years to achieve higher on-time vaccination rates, which will lead to increased numbers of cancers prevented. Health care providers are encouraged to start offering the HPV vaccine series at age 9 or 10 years. Catch-up HPV vaccination is recommended for all persons through age 26 years who are not adequately vaccinated. Providers should inform individuals aged 22 to 26 years who have not been previously vaccinated or who have not completed the series that vaccination at older ages is less effective in lowering cancer risk. Catch-up HPV vaccination is not recommended for adults aged older than 26 years. The ACS does not endorse the 2019 Advisory Committee on Immunization Practices recommendation for shared clinical decision making for some adults aged 27 through 45 years who are not adequately vaccinated because of the low effectiveness and low cancer prevention potential of vaccination in this age group, the burden of decision making on patients and clinicians, and the lack of sufficient guidance on the selection of individuals who might benefit.     

HPV genotypes in CIN 2-3 lesions and cervical cancer: a population-based study

The distribution of human papillomavirus (HPV) varies between countries and continents leading to different effectiveness of upcoming prophylactic HPV vaccines. This study analyses the HPV distribution in CIN 2-3, recurrent CIN 2-3 and cervical cancer in Iceland. About 80% of incident cases with CIN 2-3 lesions in 1990 and 1999, 99% of cancer cases in 1990-1994 and 1999-2003, and cases with recurrent CIN 2-3 after conization in 1990 were tested with PCR analysis for the presence of 12 oncogenic HPV types. About 95% of the CIN 2-3 and 92% of the cancer cases tested positive for the included HPV types. HPV 16 was the most frequent type followed by HPV 33, 31, 52, 35, 18, 58, 56, 39, 45, 59 in CIN 2-3 and by HPV 18, 33 45, 31, 39, 52, 35, 51, 56 in cancer. HPV 16 and 18 were associated with a significantly increased cancer risk and HPV 52 and 31 with decreased cancer risk compared to the risk of CIN 3. The HPV distribution differed between histological cancer types, stages and age groups. The number of HPV types was not a significant predictor of cancer. Oncogenic HPV types were found in all persistent or recurrent CIN 2-3 disease after conization. Vaccination against HPV 16/18 is estimated to achieve a minimum 40% reduced rate of CIN 2-3 and a minimum 60% reduced cancer rate. This rate could, however, be increased to 95% and 92% respectively by including all the 12 HPV types tested for in this study.     

Thin-layer liquid-based cervical cytology and PCR for detecting and typing human papillomavirus DNA in Flemish women

The objective of this study was to document the occurrence and to correlate the prevalence of different human papillomavirus (HPV) types with the cytological results on simultaneously performed thin-layer preparations in a large population of Flemish women. During 1 year, 69 290 thin-layer preparations were interpreted using the Bethesda classification system. Using an algorithm for HPV testing based on consensus primers and type-specific PCRs in combination with liquid-based cytology, we determined the occurrence and distribution of 14 different oncogenic HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68). Reflex HPV testing was performed on cytologically abnormal samples and on an age matched randomly selected control group with normal cervical cytology (n=1351). Correlation between cytology, age and prevalence for the 14 different high-risk HPV types is given. There is a significant increase in predominance of high-risk HPV types, with increasing abnormal cytology. Coinfection with multiple HPV types also increased with cytological abnormalities, and was highest in HSIL (16.7%). In Flanders, HSIL was most often associated with HPV types 16, 33, 35, 31, 18 and 51. Using thin-layer liquid-based cytology and PCR to detect HPV, it is feasible to screen large numbers of women.     

Multi-site study of HPV type-specific prevalence in women with cervical cancer, intraepithelial neoplasia and normal cytology, in England

Background:

Knowledge of the prevalence of type-specific human papillomavirus (HPV) infections is necessary to predict the expected, and to monitor the actual, impact of HPV immunisation and to design effective screening strategies for vaccinated populations.

Methods:

Residual specimens of cervical cytology (N=4719), CIN3/CGIN and cervical cancer biopsies (N=1515) were obtained from sites throughout England, anonymised and tested for HPV DNA using the Linear Array typing system (Roche).

Results:

The prevalence of HPV 16 and/or 18 (with or without another high-risk (HR) type) was 76% in squamous cell carcinomas, 82% in adeno/adenosquamous carcinomas and 63% and 91% in CIN3 and CGIN, respectively. Of all HR HPV-infected women undergoing cytology, non-vaccine HPV types only were found in over 60% of those with mild dyskaryosis or below, and in <20% of those with cancer. In women of all ages undergoing screening, HR HPV prevalence was 16% and HPV 16 and/or 18 prevalence was 5%.

Conclusion:

Pre-immunisation, high-grade cervical disease in England was predominantly associated with HPV 16 and/or 18, which promises a high impact from HPV immunisation in due course. Second-generation vaccines and screening strategies need to consider the best ways to detect and prevent disease due to the remaining HR HPV types.     

Management of HPV-positive women in cervical screening using results from two consecutive screening rounds

We studied whether triage of human papillomavirus (HPV)-positive women participating in an HPV-based screening programme can be improved by including the HPV result at the previous screen in the triage algorithm. We analyzed data of a subgroup of 366 women from the POBASCAM trial, screened by cytology and HPV cotesting. Women were included if they tested HPV-positive in the second HPV-based screening round. We evaluated the clinical performance of 16 strategies, consisting of cytology, HPV genotyping, and/or previous screen HPV result. The clinical endpoint was cervical precancer or cancer (CIN3+). The current Dutch triage testing policy for HPV-positive women is to refer women for colposcopy if they have abnormal cytology at baseline or after 6–18 months. In the second HPV-based screening round, this strategy yielded a negative predictive value (NPV) of 95.8% (95% confidence interval: 91.9–98.2) and colposcopy referral rate of 37.6% (32.3–43.2%). Replacing repeat cytology by the previous screen HPV result yielded a similar NPV (96.9%, 93.3–98.9) and colposcopy referral rate (38.8%, 33.4–44.4). A higher NPV (99.2%, 96.3–100%) at the cost of a higher colposcopy referral rate (49.2%, 43.6–54.8) was achieved when cytology was combined with HPV16/18 genotyping. The other 13 triage strategies yielded a lower NPV, a higher colposcopy referral rate or performed similarly but required additional testing. HPV-positive women in the second HPV-based screening round can be suitably managed by cytology, HPV16/18 genotyping and the HPV result at the previous screen, obviating the need for repeat testing of HPV-positive, cytology negative women.     

Cervical cancer prevention in Australia: Planning for the future

The high rate of coverage that has been achieved to date by the Australian government's Human Papillomavirus (HPV) Vaccination Program has already led to profound reductions in the prevalence of biopsy‐confirmed, high‐grade abnormalities and of vaccine‐preventable HPV types in Australia. Declines in the prevalence of vaccine preventable HPV have occurred not only in vaccinated women but also in unvaccinated women, suggesting a herd‐immunity affect. These declines were anticipated on the basis of modelling and were the major drivers for the changes proposed to the Australian National Cervical Screening Program. The federal and state‐based Australian governments established a “Renewal Steering Committee,” which conducted a literature search and a review of the available evidence to assess its applicability and quality. Together with this information the committee also used modeling to determine the optimal screening pathway for cervical cancer screening and constructed a plan for implementing the changes that will be required to transition from the currently successful screening program to the renewed program. The committee recommended that Australia move to a screening program based on testing every 5 years using an HPV test with partial genotyping with reflex liquid‐based cytology (LBC) triage for HPV‐vaccinated and unvaccinated women ages 25 to 69 years, and an additional exit test for women up to age 74 years. Primary HPV testing and reflex LBC will be funded by government. Symptomatic women outside the screening program will also be able to access government funded testing. The new screening program, to be rolled out in 2017, will also provide a cost‐effective framework for an evaluation of the national HPV vaccination program, enabling ongoing monitoring of HPV genotypes and cervical lesions in screened women. Cancer Cytopathol 2016;124:235–40 . © 2015 American Cancer Society.     

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。     

Against which human papillomavirus types shall we vaccinate and screen? the international perspective

At least 15 types of HPV have been associated with cervical cancer, but current HPV vaccines confer only type-specific immunity. To determine geographic variations in the HPV type distribution in cervical cancer, we carried out a pooled analysis of data from an international survey of HPV types in cervical cancer and from a multicenter case-control study, both co-coordinated by the IARC. Study cases were 3,607 women with incident, histologically confirmed cervical cancer recruited in 25 countries. HPV DNA detection and typing in cervical cells or biopsies were centrally done using PCR assays. Estimates of the potential number of cases prevented by HPV type-specific vaccines and changes in the validity of different HPV screening cocktails were calculated. HPV DNA was detected in 96% of specimens, and 30 different types were detected. The 15 most common types were, in descending order of frequency, 16, 18, 45, 31, 33, 52, 58, 35, 59, 56, 39, 51, 73, 68 and 66. Higher than average proportions of type 16 were found in northern Africa, of type 18 in south Asia, of type 45 in sub-Saharan Africa and of type 31 in Central/South America. A vaccine including types 16 and 18 could potentially prevent 71% of cervical cancers worldwide, but its impact with regard to the percentage of cases potentially prevented would be higher in Asia and Europe/North America. In contrast, a vaccine containing the 7 most common HPV types would prevent about 87% of cervical cancers worldwide, with little regional variation. The impact of modifying the number of types in the screening cocktail tests would be small and probably irrelevant for screening programs.