Complementary and Innovative Method in Genital HPV Testing for Cervical Cancer Prevention

Most of women diagnosed as having cervical cancer have not participated in organized cytological screening. Aim. A study was conducted to evaluate the accuracy of human papilloma virus testing by self-collected vaginal samples in comparison to regular cytological screening. The agreement of hybrid capture 2 assay and polymerase chain reaction assay for detection of human papilloma virus DNA in self-collected vaginal samples and clinician-obtained cervical smears was investigated. Forty-three women aged 23-58 years admitted for further examination due to previous positive cytology in the organized screening participated in self-collecting of vaginal samples with a novel self-sampling device. During the visit a clinician also collected a cervical smear using a cytobrush. The vaginal samples collected with the self-sampling device were analyzed for high-risk human papilloma virus with the hybrid capture 2 assay technique and the cervical smears were Pap-stained, examined cytologically and after that reanalyzed for human papilloma virus DNA using a polymerase chain reaction assay. The vaginal samples were positive for high-risk human papilloma virus in 37% of the cases using hybrid capture 2 assay. Twelve of the 43 Pap smears showed positive cytology (ASCUS-CIN 3), of which 4 showed CIN 2-3. When polymerase chain reaction assay was performed, human papilloma virus DNA was detected in 40% of the glass slides. The agreement between cytology and the two human papilloma virus testing techniques was 67-74% (kappa 0.27-0.45) and the agreement between the two human papilloma virus tests was 70% (kappa 0.36). Testing for high-risk human papilloma virus can identify more women at risk of developing cervical cancer than cytology irrespective of the sampling method. Furthermore, offering a self-sampling device for collection of vaginal smear seems to be a useful screening tool for cervical cancer among women not responding to an invitation for smear sampling.

The 7th Annual Women’s Cancer Conference, cosponsored by the City of Hope (CA, USA) and the Nevada Cancer Institute, USA, convened in November 2007 at the Wynn Hotel in Las Vegas, Nevada. Lucille Leong and Robert Morgan, both from the City of Hope faculty, co-chaired the Women’s Cancer Conference and were pleased with the 260 attendees, 20% of whom had attended a prior Women’s Cancer Conference. The 3-day Women’s Cancer Conference is primarily directed towards the general oncologist and primary care physician seeking a more in-depth understanding of new cancer treatments and practice. The presenting faculty for the 2007 meeting came predominantly from the two host institutions, with additional speakers from around the USA. The Women’s Cancer Conference follows a case-based learning format: didactic lectures are followed by a series of individual case presentations, which are discussed in detail with full audience participation. It is estimated that over 680,000 women in the USA will develop cancer in 2007 and almost 290,000 will die of the disease. Although a decline in the use of menopausal hormone therapy has resulted in a decline in new breast cancers, breast cancer remains the most common malignancy to develop in women. Improvements in screening and therapy have been credited with the improved survival of women with early stage disease. In the USA, the leading causes of cancer-related deaths are lung, colorectal, pancreas and ovarian cancers. Worldwide, cervical cancer is a major cause of cancer mortality. The first day of the conference focused on the interdisciplinary approach to gynecologic malignancies. Lectures from oncologic surgeons, medical oncologists and pathologists highlighted the diagnosis and treatment of cervical and ovarian cancers. The human papilloma virus (HPV) is an oncogenic virus and a causative agent in cervical cancer. HPV is isolated in over 99% of all cancer specimens. The WHO has declared HPV to be the first identified ‘necessary cause’ of a human cancer. Although the routine use of PAP smears has decreased the incidence and death rate in ‘resource rich’ countries, worldwide cervical cancer continues to be a leading cause of cancer death in women. After reviewing the role of HPV in the pathogenesis of cervical cancer, Sharon Wilczynski summarized diagnostic testing for HPV. The Canadian Cervical Cancer Screening Trial compared conventional cervical cytologic testing (PAP) with FDA-approved HPV DNA testing in a population of 10,154 women aged 30–69 years who presented for routine screening. The HPV DNA test was more sensitive than the PAP – 94.5 compared with 55.4% and negative predictive values of 99.8 and 100%. A Swedish trial enrolled 12,527 women to PAP alone or to HPV DNA testing (PCR-immunoassay that is not FDA approved) plus PAP. Grade 2 or 3 cervical intraepithelial neoplasia (CIN) or cancer was identified in 51% more women undergoing both tests. However, the increased sensitivity of the HPV DNA test resulted in many more

HPV vaccines in Brazil and the world

Objective: To analyze the correlation between circumcision and incidence and clearance of male genital HPV infection. Methods: From May to July 2014, 18-55 year old men who had sexual behavior history were recruited from the general population in Liuzhou, Guangxi to set up a cohort. Totally, 113 circumcised and 560 uncircumcised men were enrolled and interviewed using a questionnaire (including information on demographic characteristics and sexual behaviors), then they were followed-up with 6-month interval for 2 times. On each visit, specimens of male external genitalia were collected and genotyped for HPV DNA. The differences of incidence and clearance of genital HPV infections between circumcised and uncircumcised men were analyzed by Log-rank test. Cox regression was used to analyze the relationship between circumcision and incidence and clearance of HPV infection. Results: The median age (P(25), P(75)) of circumcised and uncircumcised men were 28 (24, 35) and 32 (24, 31), respectively. The incidences of any HPV infections were 9.1 (95%CI: 2.4-15.7) and 8.4 (95% CI: 5.6-11.2) per 1 000 person-months (χ(2)=0.10, P=0.758), respectively. The clearance of circumcised men [136.3 (95%CI: 70.0-202.7) per 1 000 person-months] was higher than that in uncircumcised men [89.6 (95%CI: 65.9-113.3) per 1 000 person-months] (χ(2)=8.19, P=0.004). In multivariate COX regression analysis, compared with uncircumcised men, circumcised men had higher possibility to clear any HPV infections (HR: 2.41, 95%CI: 1.30-4.46). Compared with men having one sexual partner, people having more than 4 sexual partners had lower possibility to clear any HPV infections (HR: 0.49, 95%CI: 0.25-0.96). Compared with 18-25 years old men, men aged 26-35 years old had higher possibility to clear high-risk HPV infections (HR: 2.14, 95%CI: 1.08-4.23). Conclusion: Circumcised and uncircumcised men had similar incidence of genital HPV infection, whereas, men conducted circumcision and having fewer sexual partners could increase the clearance of genital HPV infections.

Cervical cancer (CaCx) is a major malignancy affecting women in India. Human papilloma viruses (HPVs) have been associated with occurrence of cervical cancer. Hence, we aimed to evaluate cervical cancer burden associated with HPV infections. DNA was isolated from 100 CaCx patients. PCR was performed using degenerative primers for HPV infections as well as type-specific primers for HPV 16 and HPV 18 types. In the present cohort, 87%, 89% and 26% cases showed HPV positivity when analyzed using degenerative primers MY 09/11, GP 5+/6+ and CP I/II, respectively. While HPV 16 and HPV 18 positivity was observed in 56% and 15% cases, respectively, whereas 6% of the cases showed co-infection with both these types. All cervical cancer cases in the cohort were positive for HPV infection when analyzed by all the primer sets. The data depict significant prevalence of HR-HPV types HPV 16 and HPV 18 while also showing high prevalence of HPV infection on detection with the degenerative primer sets. Thus, suggesting that investigation of HPV infection using multiple primers sets is very crucial to avoid false-negative results.

Cervical cancer is one of the most common genital malignancies in women worldwide, although its development is largely preventable through effective primary and secondary prevention programs. The main cause of the development of this cancer is chronic infection with oncogenic types of human papillomavirus (HPV), particularly types 16 and 18. The introduction of HPV vaccination and regular screening (cytology, HPV DNA testing) has significantly contributed to the decline in incidence in developed countries. Unfortunately, in many regions of the world, including Poland, vaccination and screening rates remain inadequate, resulting in a high incidence and death rate. The standard treatment for locally advanced cervical cancer is combination chemoradiotherapy, which combines radiotherapy with the simultaneous administration of cisplatin. In recurrent and metastatic cases, where radical treatment is not possible, systemic treatment is used - mainly chemotherapy based on a combination of cisplatin and paclitaxel, often with the addition of bevacizumab, an angiogenesis inhibitor. Advances in targeted therapies and immunotherapies (e.g., PD-1/PD-L1 checkpoint inhibitors) are opening up new therapeutic options, increasing the chances of prolonging survival and improving quality of life for patients with advanced disease. Numerous clinical trials are currently underway to evaluate the efficacy of new drugs and combination treatment strategies. There is also a growing emphasis on personalizing therapy based on molecular biomarkers. Effective control of cervical cancer requires an integrated approach - combining prevention, early detection, and access to modern treatments. The future of the fight against this cancer involves global implementation of HPV vaccination, expansion of screening programs, and development of precision systemic therapies. This review synthesizes the current state of knowledge, challenges, and new directions in the prevention, diagnosis, and treatment of cervical cancer.

BACKGROUND: This study in the prospect of promoting adherence to the primary and secondary preven-tion programmes will research knowledge, attitudes and behaviors of the student population attendinghigh schools regarding HPV infections and will also promote health education sessions based on peereducation.METHODS: We carried out a community randomized trial regarding HPV infection, HPV vaccination, andsexual health, of students and a peer educational intervention.To verify the effectiveness of peer educators in changing opinions and beliefs about HPV a self-com-pletion questionnaire was made and distributed pre (T1) and post (T2) peer educator intervention. Thesame questionnaires were assigned to the control group.RESULT: The sample consisted of 900 students, mean age was 16.6±1.4, having relationship 34.4%. AtT1, 64.6% of students in experimental group said that they knew HPV, 83.4% how it is transmitted and71.1% HPV vaccination, 54.7% perceived dangerousness with significant gender-related difference. AtT2 the percentages increased. At T1, 14.1% of females were vaccinated at T2 they were 17.5%. The mainfactors associated with the students’ propensity to vaccination were: having at least one sister; being infavour of vaccinations in general; knowing that the vaccine is aimed at preventing cervical cancer; andbeing aware that they could be infected by HPV.CONCLUSION: Both the HPV test and HPV vaccine need effective communication and monitoring of thespread of knowledge, especially among women identified as most in need of information and includedin the age group at risk, in wich it is crucial to encourage informed choices. This underlines the need toplan adequate educational programmes.

Human papillomavirus (HPV) is a common sexually transmitted infection that can cause cervical, anal, vaginal, penile, and oropharyngeal cancers. There is heterogeneity in HPV prevalence across racial and socioeconomic groups as well as by age-cohort. These differences in HPV infection contribute to disparities observed in the rates of HPV-related cancer rates in these groups. This talk reviews what is known about genital, anal, and oral HPV infection, and how infection differs among groups. Reasons for disparities in HPV infection are discussed, including the roles of sexual behavior, sexual network, and co-factors (such as tobacco use). Common questions and answers about HPV infection will be discussed. Citation Format: Gypsyamber D'Souza. Disparities in HPV infection. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr IA01.

Executive SummaryThe risk of cervical cancer (CC) among women immunosuppressed for a variety of reasons is well documented in the literature. Although there is improved organ function, quality of life and life expectancy gained through use of immunosuppressant therapy, there may be increased long-te

The cancer control community is largely unaware of great advances in the control of major human cancers with vaccines, including the dramatic control of hepatocellular (liver) cancer with hepatitis B virus (HBV) vaccine, now used routinely in more than 90% of countries. The biotechnology revolution has given us a new generation of highly effective vaccines against major global killers, global funding for immunization is orders of magnitude higher than ever before, and the vaccine delivery infrastructure has improved very significantly even in the poorest countries. Liver cancer is the greatest cause of cancer deaths in men of sub-Saharan Africa and much of Asia. Even in highly endemic countries such as China, the prevalence of HB surface antigen carriers has fallen from 10% to 1%-2% in immunized cohorts of children, and liver cancer has already fallen dramatically in Taiwanese children. The Global Alliance for Vaccines and Immunization (now called the GAVI Alliance) has greatly expedited this success by providing HBV vaccine free for five years in most of the world's 72 poorest countries. HBV vaccination can serve as a model for the global control of human papillomavirus (HPV)-related cervical and other cancers with HPV vaccines. Cervical cancer is the greatest cause of cancer death in women in many developing countries; HPV vaccines are highly effective in preventing HPV infection and precancerous lesions in women, and the quadrivalent vaccine also prevents genital warts in men and women and precancerous anal lesions in men. HPV is causing a growing proportion of oropharyngeal cancers, and HPV-related noncervical cancers (penile, anal, and oropharyngeal) may exceed the incidence of cervical cancer within a decade in industrial countries, where cervical screening is effective, causing reevaluation of male HPV immunization. In developing countries, few women are screened for cervical precancerous lesions, making immunization even more important. Currently, 26 primarily industrial countries routinely immunize girls with HPV vaccine, and GAVI will begin to accept applications in 2012 to fund vaccine in developing countries that can deliver the vaccine and if GAVI can negotiate an acceptable price (one manufacturer has already offered a price of $5 per dose).

Determining the high-risk human papillomavirus (HR-HPV) genotypes burden in women with and without cervical cancer afford a direct comparison of their relative distributions. This quest is fundamental to implementing a future population-based cervical cancer prevention strategy in Ghana. We estimated the cervical cancer risk by HPV genotypes, and the HPV vaccine-preventable proportion of cervical cancer diagnosed in Ghana. An unmatched case-control study was conducted at the two largest cervical cancer treatment centres in Ghana from 1st October 2014 to 31st May 2015. Cases were women diagnosed with cervical cancer and controls were women without cervical cancer who were seeking care at the two hospitals. Nested multiplex polymerase chain reaction (NM-PCR) was used to detect HPV infection in cervical samples. Logistic regression was used to determine the association between the risk of cervical cancer and identified HPV infection. P ≤0.05 was considered statistically significant. HPV deoxyribonucleic acid (DNA) data were analysed for 177 women with cervical cancer (cases) and 201 without cancer (controls). Cervical cancer was diagnosed at older ages compared to the age at which controls were recruited (median ages, 57 years vs 34 years; p < 0.001). Most women with cervical cancer were more likely to be single with no formal education, unemployed and less likely to live in metropolitan areas compared to women without cervical cancer (all p-value <0.001). HPV DNA was detected in more women with cervical cancer compared to those without cervical cancer (84.8% vs 45.8%). HR-HPV genotypes 16, 18, 45, 35 and 52 were the most common among women with cervical cancer, while 66, 52, 35, 43 and 31 were frequently detected in those without cancer. HPV 66 and 35 were the most dominant non-vaccine genotypes; HPV 66 was more prevalent among women with cervical cancer and HPV 35 in those without cervical cancer. Cervical cancer risk was associated with a positive HPV test (Adjusted OR (AOR): 5.78; 95% CI: 2.92-11.42), infection with any of the HR-HPV genotypes (AOR: 5.56; 95% CI: 3.27-13.16) or multiple HPV infections (AOR: 9.57 95% CI 4.06-22.56). Women with cervical cancer in Ghana have HPV infection with multiple genotypes, including some non-vaccine genotypes, with an estimated cervical cancer risk of about six- to ten-fold in the presence of a positive HPV test. HPV DNA tests and multivalent vaccine targeted at HPV 16, 18, 45 and 35 genotypes will be essential in Ghana's cervical cancer control programme. Large population-based studies are required in countries where cervical cancer is most prevalent to determine non-vaccine HPV genotypes which should be considered for the next-generation HPV vaccines.

HPV Genotype Detection Using Hybrid Capture Sample Preparation Combined with Whole Genome Amplification and Multiplex Detection with Luminex XMAP

To compare human papillomavirus (HPV) DNA detection in self-collected vaginal and urine samples with clinician-taken cervical samples in relation to histology. Self-collected vaginal, urine and clinician-taken cervical samples were analyzed from 218 women with the Cobas 4800 HPV test (Roche Molecular Diagnostics). The sensitivity for detection of HPV in the vaginal self-sampling test was 96.4% and in urine was 83.9% relative to detection by clinician-taken cervical sample. The vaginal self-sampling and the clinician-taken HPV tests had the same sensitivity of 92.8% (95% confidence interval=86.3-96.8%) and specificity for detection of high-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS). Detection in urine samples had a sensitivity of 76.3% (95% confidence interval=67.9-84.2%) for HSIL/AIS. The Cobas 4800 HPV test detects high-grade pre-cancerous cervical lesions in self-collected vaginal samples with the same high sensitivity as in clinician-taken cervical samples.

The purpose was to evaluate the diagnostic effectiveness of High-risk human papillomavirus(hrHPV) testing, DNA methylation, PAX1/ZNF671 methylation in triaging patients with abnormal cytology and/or abnormal cervical biopsy pathology in cervical cancer screening; And the detection performance of different screening strategies was compared among clinician-taken cervical scrapes and paired self-collected urine and vaginal samples. A total of 136 urine-based,137self-collected vaginal and 140 cervical scrapes samples were analyzed. Samples were tested for hrHPV DNA and six methylation markers. Various screening strategies from different samples were compared under the definitive histopathology for their diagnostic accuracy against two standards: cervical intraepithelial neoplasia grade 2 or more severe lesions (CIN2+) and cervical intraepithelial neoplasia grade 3 or more severe lesions (CIN3+). For PAX1 and ZNF671, the areas under the ROC curve were 0.929 and 0.862 and the methylation-positive rate was 89.5% (77/86) and 80.2% (69/86) in CIN3+ lesions. The cutoff values were 7.95and 10.92, respectively, with the highest Youden index values being 0.763 and 0.684, respectively. The sensitivity of hrHPV testing for CIN2+ was 89.80% in cervical scrape to 92.63% in self-collected vaginal samples. And the optimal marker panel (PAX1/ZNF671) resulted in an 85.8% sensitivity and 5.8 PLR for CIN2+ detection in cervical scrapes, and reached a highest sensitivity for CIN3+ in cervical scrapes (91.9%), markedly exceeding that of vaginal (71.4%) and urine (48.1%) samples (P<0.001). The Negative Predictive Value (NPV) for cervical scrapes (85.7%) was higher than self-collected alternatives (P<0.001). As for hrHPV and DNA Methylation, a perfect sensitivity (96.51%), NPV (90.00%) and Negative Likelihood Ratio(NLR) (0.07) for CIN3+ were reached. For hrHPV negative population, trough PAX1/ZNF671 detection, Cervical scrapes showed a highest sensitivity (100.00%) and specificity (91.30%), a 77.78% PPV and 100% NPV were achieved for discriminating CIN3 +. The prevalence of methylation for PAX1/ZNF671 genes exhibited a strong positive correlation with the severity of cervical lesions, and demonstrates a better diagnostic value for CIN2+ lesions. DNA methylation testing, especially PAX1/ZNF671 offers a promising strategy to detect CIN2/3 lesions or more serious disease. Cervical samples were the perfect candidates for DNA methylation. Furthermore, PAX1/ZNF671 methylation assays had a strong capacity in screening and excludingCIN2+ lesions among HPV-negative individuals.

It was proven in the early 1980s that cervical cancer (CC) biopsy specimens and CC cell lines contain human papillomavirus (HPV) DNA sequences. In subsequent years, researchers discovered that the E6 and E7 genes of HPV are expressed in CC tissues and these oncoproteins interact with cellular proteins, including pRb and p53. Establishment of the relationship between HPV infections and CC led to increasing interest on this topic. Comprehensive epidemiological studies determined that specific types of HPV are major risk factors for CC. These HPV types, called high-risk or oncogenic types, are associated with other anogenital cancers and a subset of head and neck cancers. A number of commercial and in-house diagnostic techniques, each of which has a different approach and methodology, have been developed to diagnose HPV infections. HPV testing based on the detection of viral DNA has become an important part of CC screening programs. These screening-typing methods and combined approaches, which are used to diagnose and follow-up (management) HPV infections, have advantages and disadvantages. The choice of method is complicated by several factors and challenges that arise owing to the nature of the virus and the assay methodology. For example, a number of different HPV types can cause genital infections, multiple sequence variations are often observed even in the same HPV genotype, the detection sensitivity of the available methods is variable depending on the HPV genotypes and the viral DNA copy number in the samples examined. The capability for the detection of multiple infections and the ability to perform genotyping differ between the methods. The aim of this review is to summarize the methods used for the diagnosis and follow-up of HPV infections, and to share the current informations that may be helpfull for the choice of appropriate method. For this purpose, molecular-based HPV tests that were used in the past and their development processes were described briefly, then currently accepted and widely used methods for diagnosis, screening, and typing were discussed in detail, along with their advantages and disadvantages.