Human papillomavirus genotype prevalence in cervical biopsies from women diagnosed with cervical intraepithelial neoplasia or cervical cancer in Melbourne, Australia

Multicenter international phase III clinical trials using multivalent human papillomavirus (HPV) vaccines for cervical cancer (CC) prevention are underway. As HPV immunity is type specific, defining HPV genotype prevalence in different regions to ascertain whether predominant types differ geographically is considerably important prior to vaccine implementation. This study aimed to define HPV genotypes present in CC and high-grade dysplasia among women in Melbourne, Australia. HPV genotype analysis of a cross section of women in Melbourne with cervical dysplasia/cancer was performed. A total of 493 cervical biopsies from patients being treated for moderate (n= 122) or severe (n= 180) cervical intraepithelial neoplasia (CIN II/III) or CC (n= 191) were tested for HPV genotypes using the PGMY09/11 primer system and line blot assay. HPV detection rates were 63.9%, 72.8%, and 86.9% in CIN II, CIN III, and CC biopsies, respectively. The most prevalent HPV genotypes among CC biopsies were HPV-16 (52.9%), HPV-18 (18.3%), HPV-45 (6.3%), HPV-39 (3.1%), and HPV-73 (2.6%). Multiple HPV infections, comprising two to five types, were identified in 14.4% of biopsies, being significantly fewer (5.2%) among CC biopsies (P < 0.0001). These results indicate that the two most prevalent CC-associated HPV genotypes in Australia parallel those described internationally, with type variations thereafter.     

Molecular variants of human papillomavirus type 16 and risk for cervical neoplasia in South Africa

Non-European variants of human papillomavirus (HPV) type 16 are generally associated with a greater risk of cervical neoplasia than European prototype variants. We investigated whether this association would persist in a population in which non-European HPV 16 variants were more common. We sequenced HPV 16 isolates in cervical samples collected from 93 Black South African women enrolled in a cervical cancer screening study and examined associations between cervical neoplasia identified though colposcopy with cervical biopsy and the specific HPV 16 variant identified. The European prototype variant (EP) was the most commonly identified variant in this population (47% of all isolates), but African variants (Af-1 and Af-2) were also quite common (41% of all isolates). In contrast to previous studies, we found no evidence that non-European variants were associated with an increased risk of neoplasia. Rather, most of the HPV 16-associated cancers were found in association with EP (71% of 14 cases). In this setting where African HPV 16 variants were common, no increased risk for cervical neoplasia was found among women with these variants compared with other HPV 16 variants.     

Human papillomavirus and cervical cancer from a prospective study in Khon Kaen, Northeast Thailand

The risk of developing carcinoma of the cervix in women infected with human papillomavirus (HPV) was estimated in a nested case-control analysis of 33 cancers (invasive and in situ) and 113 controls, matched by age and sex, from an ongoing cohort study of lifestyle and cancer in a rural population of Northeast Thailand. Oncogenic HPV types were present in 10.8% of control women and in 31/33 of the carcinoma cases, corresponding to an odds ratio of 130.6 (95% CI 11.7-1457.0). There was no significant difference in risk between prevalent cancer cases (diagnosed less than 3 months after HPV testing) and incident cases (diagnosed an average of 2.1 years later). HPV 16 and 18 were the most prevalent oncogenic HPV types present. The results confirm that some two of three of cervical cancer cases in this population of Northeast Thailand are caused by HPV 16 and 18.     

Human papillomavirus status in advanced cervical cancer: predictive and prognostic significance for curative radiation treatment

Human papillomavirus (HPV) infection plays a major role in oncogenesis of squamous cell carcinoma of the cervix. This study was performed to investigate if HPV status and E2 gene integrity are prognostic parameters for clinical outcome and predictive for radiation response. Forty women with locally advanced cervical cancer treated with curative radiotherapy were analyzed for HPV infection and E2 gene integrity by multiplex polymerase chain reaction. Statistical analyses were performed for overall survival, disease-free survival (DFS), local progression-free survival, and treatment response (clinical complete remission). Twenty-eight (70%) of 40 carcinomas were HPV positive. The only significant factor for a better overall survival, DFS, and local progression-free survival was HPV positivity (P < 0.02, P= 0.02, and P < 0.05, log-rank, respectively). HPV-positive tumors had a significantly better clinical complete remission (67% vs 33%, P= 0.04, Fisher's exact test). An intact E2 gene region showed a trend for a better DFS (P= 0.1, log-rank). This study reveals HPV as an independent prognostic parameter for outcome and radiation response. Integration of the virus genome into host cell DNA might be a molecular target to determine the treatment response of HPV-positive cancers.     

Human papillomavirus,cervical screening and ethical considerations

Human papillomavirus (HPV) is an extremely prevalent virus linked to multiple cancers, but most notably cervical cancer. The cervical screening programme in the UK has developed significantly since it was first introduced in 1964. This, together with the introduction of HPV vaccination, has made a huge difference to the early diagnosis and mortality for cervical cancer patients. Uptake of screening is paramount and this article addresses the barriers to this, and how these might be overcome. Other ethical issues around the topic of HPV, vaccination and screening include discrimination around sexual behaviour and orientation, education, vaccination availability and vertical transmission. This is an area of medicine that continues to develop and evolve as we understand more about HPV and how to tackle it.     

Human papillomavirus prevalence and predictors for cervical cancer among high-risk women from Rio de Janeiro, Brazil

We assess the prevalence of human papillomavirus (HPV) and cofactors for cervical severe disease, as contribution for vaccine strategies at the right moment in which Brazilian health authorities have approved an anti-HPV vaccine. A case-control study was undertaken with 201 women who attended a public health service with previous abnormal cytology. The HPV status was ascertained by consensus primers My09/11 and typed by 6, 11, 16, 18, 31, 33, 35, and 58 specific primers. Patients diagnosed with high-grade squamous intraepithelial lesions (HSIL) and cervical cancer were referred as cases (n = 84). Patients with normal/inflammatory cervix or carrying benign cervical lesions were included in controls (n = 117). The overall prevalence of HPV infection was 75.6%, with 91.7% among cases. In spite of HPV 16 being the most frequent type (53.3%), 27.6% of infections were attributed to nonvaccine types. High-risk HPV were strongly associated to older women (OR = 6.7). Otherwise, age at the first intercourse (OR = 7.10), three or more parities (OR = 3.05), abortion episodes (OR = 4.80), and smoking (OR = 3.83) conferred a heavy effect in younger women. Among mediators affecting the progress from HSIL to cancer, age played the main role in easing the progression (OR = 1.09, P = 0.002) followed by education level (OR = 4.20, P = 0.066). White ethnia showed to be a protective factor (OR = 0.32, P = 0.055). Predictors from HPV exposure to malignant disease include demographic and behavioral factors. Public policies such as improvement of education and continued prevention campaigns might contribute to reduce this picture. This work also gives background, in identifying a target population, for implementing future vaccine strategies.     

广西沿海地区妇女宫颈癌患者人乳头瘤病毒（HPV）感染各亚型分布特点

目的探讨广西沿海地区妇女宫颈癌患者人乳头瘤状病毒（human papillomavirus,HPV）感染分布情况及主要型别,为广西沿海地区临床防治宫颈癌、研制适合该地区的预防性HPV疫苗提供理论依据。方法采用人乳头瘤病毒核酸扩增分型检测试剂盒方法,对76例广西沿海地区妇女经病理确诊宫颈癌患者的宫颈脱落细胞进行HPV基因分型检测。结果 76例宫颈癌患者中有69例HPV阳性,阳性率为90.8%,其中,HPV16感染率最高为56.5%,其他高危型的感染率从高到低依次为HPV18、33、58、52、53、31、45、35、39、51、56、66、68。低危型中HPV6型感染率最高为5.8%,其他低危型的感染率从高到低依次为HPV11、43、44。多重感染率为20.3%。正常对照组60例中有13例HPV阳性（21.7%）。其中,13例阳性标本中,HPV16感染率最高为30.8%,其他高危型HPV31、52、53感染率为15.4%,低危型HPV11、43、44感染率为7.7%。宫颈癌HPV阳性率明显高于正常对照组,差异有统计学意义（P〈0.005）。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,可能是广西沿海地区妇女宫颈癌较易感染的型别。     

Human papillomavirus type 16 E6 and E7 gene variations in Indian cervical cancer

OBJECTIVES: Human papillomavirus type 16 is a causative factor for development of cervical cancer. The E6 and E7 genes of HPV 16 are critical to the process of immortalization and transformation of host cells. Recent reports suggest that variants of these two genes may contribute to the risk of malignant progression of cancer in the uterine cervix. However, no data exist on sequence variations of HPV 16 E6 and E7 genes that may exist in India. Therefore, we examined intratype variations in the E6 and E7 viral genes in DNA isolated from HPV 16-positive cervical scrapes and biopsies. METHODS: The open reading frames of the E6 and E7 genes were amplified by PCR and then directly sequenced by the fluorescent dye dideoxy termination method.Results. In addition to the prototype E6 gene sequence, five sets of mutations of the E6 gene were identified. The European prototype (350T) was detected in 9.1% of the study group while the European variant (350G) was seen in 28% of patients. The remaining variants (a combination of the 350G mutation with 335T, 145T, or 419G) were significantly associated with cases compared to controls. The 350G + 145T variant was found at much higher incidence in cases in younger women, suggesting that this variant may be associated with aggressive tumor behavior. Interestingly the 350G + 419G combination was found only in controls. There was no significant association between the four genotypes of E7 and any stage of tumor progression or age. CONCLUSIONS: The results indicate that specific mutations in the E6 gene are found in young Indian women with high-grade squamous intraepithelial lesions and invasive cancer, suggesting that these mutations represent more oncogenically active HPV 16. Whether this increased oncogenecity is due to differences in p53 inactivation, ineffective keratinocyte differentiation, and/or altered response to the immune system by these oncogenic E6 mutants remains to be clarified.     

A study of women's knowledge regarding human papillomavirus infection, cervical cancer and human papillomavirus vaccines

AIMS: Human papillomavirus (HPV) infection is a common sexually transmitted viral infection and is associated with the development of cervical cancer. HPV vaccines are now undergoing phase 3 clinical trials in Australia. It is likely that an HPV vaccine will become licensed for use in the near future. METHODS: Ninety women aged 18-30 years from three different groups (those attending a dysplasia clinic, a local university health service and participants currently involved in a phase 3 HPV vaccine trial) completed a questionnaire assessing their knowledge base regarding HPV infection, cervical cancer, Pap tests and HPV vaccines. RESULTS: Respondents demonstrated good understanding of the Pap test and interpretation of an abnormal result. Most respondents (89%) had heard of HPV and attributed a number of different clinical symptoms to infection. For women who had not heard of an HPV vaccine, 79% of respondents stated that the most common resource they would use to obtain further information is their general practitioner. DISCUSSION: Many women do not understand the risk factors for HPV infection, the clinical problems it may cause and the potential long-term complications of infection. Few women have heard of a HPV vaccine, but most women surveyed would approach their general practitioner for more information if one became available. CONCLUSION: This study highlights the need for further education regarding HPV infection and the potential long-term complications such as cervical cancer. It also demonstrates that education of general practitioners regarding an HPV vaccine is essential, as this is the most likely resource women will use to obtain further information in the future.     

Human papillomavirus

Human papillomaviruses are ancient small DNA viruses and represent the most common sexually transmitted infection in the world. In the majority, HPV infection is cleared by an incompletely understood immune response. HPV is a necessary but not sufficient cause of cervical cancer, and responsible for a proportion of other anogenital cancers including vulval, vaginal, anal and oropharyngeal. Oncogenesis is likely mediated through viral proteins which hijack host-cell machinery in epithelial keratinocytes and disrupt host tumour-suppressor proteins. Much work has been undertaken to further characterise the natural history of HPV infection and cervical disease. Such efforts have been translated to important public health interventions like the introduction of HPV tests in cervical screening. HPV vaccination programmes are expected to further reduce the incidence of high-risk HPV infections and resultantly HPV-related disease.     

Human papillomavirus (HPV) genotyping by HPV DNA chip in cervical cancer and precancerous lesions

OBJECTIVES: The human papillomavirus (HPV) is a well-known cause of cervical cancer. HPV tests are used as an adjunct test to decrease the false-negative rate of cytological screening. However, attempts are being made to replace the cytological screening with HPV tests. Therefore, this study was performed to examine the possibility of using HPV tests as screening test. MATERIALS AND METHODS: The results of the tests that were performed at the same time including the ThinPrep cytology, the high-risk group hybrid capture II (HC-II) test, the HPV DNA chip (HD-C) test, and a punch biopsy were compared in 400 women who were referred to us due to abnormal cytology or cervicogram. The accuracy of each test was then evaluated, and the type of virus was investigated using a HD-C test. RESULTS: The positive predictive values detected by the high-risk group HC-II test and HD-C test according to the histological diagnosis outcomes were 56.8 and 53.8%, respectively, for cervicitis; 91.5 and 91.5%, respectively, for cervical intraepithelial neoplasia I (CIN I); 88.1% and 81.0%, respectively, for CIN II; 88.6 and 84.2%, respectively, for CIN III, and 92.5 and 88.7%, respectively, for cancer (in 53 patients). The most prevalent types of HPV according to the HPV tests were types 16, 58, 18, and 52 in which type 16 was detected in the more advanced lesions. The sensitivity was 88.4% for the ThinPrep cytology, 89.9% for the HC-II for the high-risk group, and 86.2% for the HD-C test. CONCLUSION: These results suggest the possibility of using the HC-II and HD-C tests as screening tests, which have a similar sensitivity as the ThinPrep cytology. Nonetheless, randomized controlled trials will be needed before the actual application of the HPV tests as screening tests. Despite the fact that the importance of HPV type 16 in cancer development was confirmed, the prevalence of types 58 and 52 were relatively high compared with those found in other studies, showing a need for further studies on this subject. These HPV types need to be considered in vaccine development.     

Prevalence and genotypes' distribution of human papillomavirus in invasive cervical cancer in Saudi Arabia

Objective

Data concerning HPV infection in cervical cancer are globally lacking in Saudi Arabia. Therefore, the aim of this study was to assess HPV prevalence and genotypes' distribution in invasive cervical cancer in our patients to provide baseline information for screening and prevention.

Methods

The study included 100 paraffin-embedded cervical tumors. HPV genotyping was performed using the Linear Array kit (Roche Diagnostic) that enables the concomitant detection of 37 mucosal HPVs including 13 most common high-risk viruses.

Results

Eighty-nine specimens were HPV-positive. Eleven different HPV genotypes were detected, 8 high risk (16, 18, 31, 39, 45, 51, 59, 73) and 3 low risk (6, 64, 70). Ten patients had double infections involving mainly HPV-16 and 18. The most common genotypes were 16 (65.2%), 31 (7.9%), 45 (6.7%), 18 (3.4%), and 73 (2.3%). However, by considering double infections, HPV-18 became the second most common genotype (10.1%). The patients' median age was significantly lower (P = 0.028) in HPV-16/18 infected group compared to other genotypes (44, range 32-76 vs. 49, range 38-67).

Conclusions

Eighty-nine percent of cervical cancers in Saudi Arabia were associated with HPV infection, and 78.7% (70/89) of HPV-positive tumors were infected with HPV-16/18, which caused the cancer to appear 5 years earlier than the combined HPV-negative and other HPV genotypes (P = 0.013).     

人乳头状瘤病毒不同亚型感染与宫颈病变的相关性

目的 了解门诊高危人群和宫颈病变患者的人乳头状瘤病毒（HPV）感染的型别分布，探讨不同HPV亚型感染的致癌性。方法 采用导流杂交技术，对门诊就诊的1715名有性生活史妇女，进行下生殖道HPV感染分型筛查。其中463例经阴道镜下定点官颈活检，病理确诊分为官颈炎症234例、CINⅠ96例、CINⅡ80例和CINⅢ53例。分析人群HPV感染的型别分布、与宫颈病变相关性。结果 21种HPV亚型均被检出，1715名门诊妇女中HPV阳性率57．1％（978／1715），宫颈病变中为76．9％（356／463），而在CINⅢ中达98．1％（52／53）。常见的5种亚型分布：高危人群为HPV16、58、52、33和6型；宫颈病变为HPV16、58、52、33和31型；CINⅢ中为HPV16、33、58、31和52型。HPV16、33和31型与宫颈病变程度相关（P〈0．05），Logistic回归分析，高级别鳞状上皮内瘤变（HSIL，CINⅡ＋CINⅢ）的主要风险也是感染HPV16、33和3l型（OR9．59、2．99和2．52，95％CI4．805～11．989、1．231～7．296和1．174～5．429）。结论 本地区官颈病变的常见型别是HPV16、58、52、33和31型，HPV16、33和31型是HSIL的主要致病型。     

Human papillomavirus infection: an old disease, a new vaccine

Human papillomavirus (HPV) infection is common and causes a wide spectrum of disease. With recent advances in the development of prophylactic HPV vaccines, it is likely that these will be licensed for use in the near future. This review focuses on the science behind HPV vaccines, published clinical trial results for both prophylactic and therapeutic HPV vaccines, important issues relevant to implementation and cost-effectiveness models of HPV vaccination programs. It may be that an HPV vaccine that protects against the complications of HPV infection such as cervical cancer will be one of the most significant public health initiatives of this decade.     

Human papillomavirus vaccination in the resourced and resource-constrained world

Human papillomavirus has been established as the causal agent for cervical cancer. The identification of a clear cause presents an unparalleled opportunity for cancer control. As such, the development of prophylactic human papillomavirus vaccines has been rightly hailed as one of the significant scientific triumphs of the past 20 years. This story of scientific triumph over disease, however, is not yet complete. The fruit of scientific labour must be delivered to the people in order to fulfil the underlying intent of the research (i.e. to prevent cancer and save lives). The success of a vaccination programme, however, does not depend on the biological efficacy of the vaccine alone. Various other local factors, such as poverty, gender inequality, cultural traditions, or religious beliefs, can significantly constrain the success of any vaccination programme. In this chapter, we provide an overview of how the human papillomavirus vaccine works and its global uptake, as well as, how variations in local contexts can affect the successful implementation of a vaccination programme. Other factors besides vaccine costs also need serious attention. With better understanding of such factors, policy makers and medical health professionals will be better equipped to make informed decisions to maximise the potential benefits of the human papillomavirus vaccines for the most number of people in individual countries.     

Human papillomavirus detection in self-collected vaginal specimens and matched clinician-collected cervical specimens

Human papillomavirus (HPV) detection is an integral part of cervical cancer screening, and a range of specimen collection procedures are being tested. Preliminary studies have found that the majority of women prefer self-collection of vaginal specimens instead of clinician-collected specimens of the cervix. The purposes of the current study were to explore the social and behavioral predictors of acceptance of self-collection of vaginal specimens among patients and to assess concordance in detection of HPV between clinician-collected cervical specimens and self-collected vaginal specimens. The study was conducted at a university family medicine clinic using a cross-sectional study design, and enrollment of women presenting for routine gynecological examination consecutively in a period of 1 year, self-administered questionnaires, collection of paired vaginal and cervical specimens for HPV DNA using Hybrid Capture 2, and cytologic analysis. Most women (79.8% [398/499]) agreed to collect vaginal specimens. In our study, 76.6% (216/282) African American women (AA), 88.1% (156/176) white non-Hispanic (WNH) women, and 63.4% (26/41) women of other races (P < 0.0001) agreed to self-collect vaginal specimens. HPV was detected in 16.0% (80/499) of clinician-collected cervical specimens and 26.1% (104/398) of self-collected vaginal specimens (P < 0.001). HPV detection was concordant in 13.4% (53/398) women in both cervical and vaginal specimens. Self-collection of vaginal specimens for HPV DNA detection is acceptable to most women presenting for routine gynecological examination. WNH women were more likely to obtain self-collected specimens than AA women. Vaginal specimens were more likely to be positive for HPV than were cervical specimens.