Prevention Of HPV-associated Cancers Research Articles

Epidemiology of HPV-associated cancers past, present and future: towards prevention and elimination.

Cervical cancer is the first cancer deemed amenable to elimination through prevention, and thus lessons from the epidemiology and prevention of this cancer type can provide information on strategies to manage other cancers. Infection with the human papillomavirus (HPV) causes virtually all cervical cancers, and an important proportion of oropharyngeal, anal and genital cancers. Whereas 20th century prevention efforts were dominated by cytology-based screening, the present and future of HPV-associated cancer prevention relies mostly on HPV vaccination and molecular screening tests. In this Review, we provide an overview of the epidemiology of HPV-associated cancers, their disease burden, how past and contemporary preventive interventions have shaped their incidence and mortality, and the potential for elimination. We particularly focus on the cofactors that could have the greatest effect on prevention efforts, such as parity and human immunodeficiency virus infection, as well as on social determinants of health. Given that the incidence of and mortality from HPV-associated cancers remain strongly associated with the socioeconomic status of individuals and the human development index of countries, elimination efforts are unlikely to succeed unless prevention efforts focus on health equity, with a commitment to both primary and secondary prevention.

Reasons patients cite to their healthcare provider for not initiating or completing HPV vaccination.

Vaccination against the human papillomavirus (HPV) is critical to the prevention of HPV-associated cancers. This study aimed to describe the reasons cited by patients for not initiating or completing the HPV vaccination series, as reported by healthcare providers. Study data was obtained from a University of Texas MD Anderson Cancer Center population-based cross-sectional survey of healthcare providers practicing in Texas. Prevalence estimates of reasons cited for not initiating or completing HPV vaccination were estimated by patient population (i. parents of children and ii. adult patients). The study included 973 primary care providers, of which 45.53% were physicians and 54.47% were mid-level care providers. For parents who did not initiate the HPV vaccine for their child, the most commonly cited reasons were the belief that the vaccine was not needed (52.54%, 95% CI: 48.90-56.15), that the child was not sexually active (52.54%, 95% CI: 48.90-56.15), and safety concerns/side effects (47.05%, 95% CI: 43.44-50.69). Among age-eligible adults who did not initiate HPV vaccination, lack of knowledge and awareness was the most commonly cited reason (30.52%, 95% CI: 27.71-33.50). For non-completion of the HPV vaccine series, competing priorities was most commonly cited by parents (41.29% 95% CI: 37.76-44.91), followed by adverse reactions after the first dose (16.05%, 95% CI: 13.56-18.90). For non-completion of the HPV vaccine series among adults, competing priorities was also the most cited reason (31.04%, 95% CI: 28.20-34.02). These findings highlight the importance of addressing misconceptions and improving education about HPV vaccination to increase vaccination uptake rates and prevent HPV-related cancers.

Characterization of a conserved cysteine residue in the papillomavirus E2 protein

Background:Human papillomaviruses (HPVs) are DNA tumor viruses that infect cutaneous and mucosal epithelium. While most infections are self-limiting, a small subset that infects the mucosal epithelium progresses to cancer. All papillomaviruses encode the protein E2 which regulates viral transcription and replication; a highly conserved cysteine residue in the DNA contact helix of E2 plays an unknown role. Previous research suggests the residue is not necessary for replication or binding to DNA. We hypothesize that post-translational modification of this conserved cysteine residue leads to release of viral DNA during packaging of progeny virions.
 Methods:Mutations of the murine papillomavirus conserved E2 C307 residue to serine and phenylalanine were used to investigate its role in E2 function. C33A, HPV negative cervical cancer cells, were transfected with an E2-responsive luciferase reporter and either wild type or mutant C307 E2 vectors; luciferase assays were performed 48 hours post-transfection to assess transcriptional activity. Whole cell lysates from overexpressed C307 mutants were separated by SDS-PAGE and immunoblotted to assess expression levels relative to wild type. To examine protein localization, C33A cells were transfected with equal amounts of wild type or mutant E2 and fixed 48 hours post-transfection for immunofluorescence.
 Results:C307S and C307F mutants are both capable of weakly activating transcription. Overexpression of the mutants resulted in a dose dependent increase in transcriptional activity. Both mutants are expressed at levels comparable to wild type E2 and are correctly localized to the nucleus.
 Conclusion/Impact:The deficient transcription function displayed by the C307 mutants cannot be explained by poor expression or mislocalization. Continued study of this conserved cysteine will help to further understanding of papillomavirus biology and may offer insight into novel avenues for treatment or prevention of HPV-associated cancers.

Evaluation of the Novaplex II HPV28 Detection Assay for HPV Typing in Formalin-Fixed, Paraffin-Embedded Tissues

Prophylactic human papillomavirus (HPV) vaccines are recommended for prevention of HPV-associated cancers. Type-specific detection of HPV in formalin-fixed, paraffin-embedded (FFPE) tissues retrieved from diagnostic pathology laboratories is important in monitoring the impact of HPV vaccines. However, few typing assays have been validated for testing FFPE samples. Results of the Novaplex II HPV28 Detection (Novaplex) assay were compared with those from the reference assay (Linear Array with reflex Line Probe Assay) on 708 FFPE samples from cervical lesions. Novaplex showed high type-specific concordance with the reference method for HPV16/18, 9 types targeted by the Gardasil 9 vaccine, 14 high-risk types, and 21 types covered by comparison assays. The rate of inadequate samples was low in both approaches (reference, 3.4%; Novaplex, 1.7%). The proportion of discrepant types was less than 3.5% and positive concordance was greater than 75.0%. Furthermore, the type-specific positive agreement (92.0% to 98.0%), negative agreement (96.0% to 99.0%), and accuracy (97.0% to 99.0%) was high. Cohen's κ ranged from 0.86 to 0.89, indicating excellent agreement between Novaplex and reference assays. The results show that Novaplex is a suitable method for detection of HPV in FFPE tissues.

Barriers to HPV Vaccination Among Korean Men in the United States.

Human papillomavirus (HPV) vaccination disparities may exacerbate the substantial racial and ethnic variations in rates of HPV-associated cancers. To reduce these disparities, special attention must be paid to increasing vaccine uptake among subgroups of Asian American men and women who are less likely to engage in primary prevention of HPV-associated cancers. Because nurses are often involved in vaccine discussions, they can play a critical role in improving HPV vaccine uptake by providing culturally appropriate and responsive messages to their patients.

Acceptance of the HPV Vaccine in a Multiethnic Sample of Latinx Mothers.

This descriptive qualitative study explored Latinx mothers' acceptance of the human papillomavirus (HPV) vaccine for their adolescent children. Data were collected through individual, semi-structured interviews and analyzed using a hybrid method of thematic analysis that incorporated deductive and inductive approaches. Twenty-two (n = 22), mostly foreign-born, Latinx mothers of male and female adolescents participated in the study. Three main themes and nine subthemes emerged from the analyses. Findings identified the need for increased efforts to raise awareness and knowledge among Latinx mothers of the direct benefits of the HPV vaccine for sons, including stressing prevention of HPV-associated cancers in males. Findings also underscore the need for improved health care providers' communication and recommendation of the HPV vaccine for Latinx adolescent males. Future research should intervene upon the study's findings to address barriers that remain and affect Latinx mothers' acceptance and uptake of the HPV vaccine for their children, in particular their sons.

“I don’t Think He Needs the HPV Vaccine Cause Boys Can’t Have Cervical Cancer”: a Qualitative Study of Latina Mothers’ (Mis) Understandings About Human Papillomavirus Transmission, Associated Cancers, and the Vaccine

Genital human papillomavirus (HPV) is the most common sexually transmitted virus in the United States and etiologically linked to several types of cancers including the cervix, vulva, vagina, penis, anus, and oropharynges. Evidence indicates certain types of HPV-associated cancers disproportionally affect Latinos in the United States. This qualitative study sought to explore Latina mothers' perceptions and understanding of HPV infection, HPV-associated cancers, and the HPV vaccination for their adolescent sons and daughters. Twenty-two individual, face-to-face interviews were conducted in 2018-2019 with mothers who had at least one child between the ages of 11 and 19years. Data were analyzed using a hybrid method of thematic analysis that incorporated deductive and inductive approaches. Two major themes emerged from the analysis: (1) mothers' (mis) understanding about HPV infection transmission and HPV-associated cancer risk for girls and boys, and (2) mothers' (mis) understandings about the HPV vaccination for girls and boys. Results found that most mothers had inadequate understanding of HPV transmission, HPV-associated cancer risk for males, and need to vaccinate boys against the virus for their own personal health and prevention of HPV-associated cancers. Findings suggest that interventions should focus on improving Latina mothers' understanding of HPV transmission, addressing the lack or inadequate knowledge about HPV-associated cancer risk for males, as well as misconceptions about the importance of the HPV vaccination for males for their personal health and the prevention of HPV-associated cancers. Future research should quantify Latino parents' awareness, knowledge, and acceptability of the HPV vaccine for their sons and daughters.

Central American Immigrant Parents' Awareness, Acceptability, and Willingness to Vaccinate Their Adolescent Children Against Human Papillomavirus: A Pilot Cross-Sectional Study.

Despite increasing interest in understanding the factors influencing awareness and acceptability of the human papillomavirus (HPV) vaccine among Latino parents, to date limited information is available specific to Central American parents living in the United States (US). Therefore, this pilot cross-sectional study was designed to explore and assess Central American immigrant parents’ awareness, acceptability, and willingness to vaccinate their children against HPV, and interest in participating in future HPV-associated cancer prevention study. Fifty-six Central American parents, majority immigrant (96.4%; n = 54) from four countries, El Salvador—50% (n = 27); Guatemala—25.9% (n = 14); Honduras—22.2% (n = 12); and Panama—1.9% (n = 1) participated in this study. Participants completed an interviewer-administered questionnaire survey in their preferred language (i.e., Spanish or English). A little over half of the participants were mothers (57.1%; n = 32) and parents’ mean age was 43.2 years (SD = 6.4). The majority was married or cohabitating (76.8%, n = 43), and 39.3% (n = 22) reported having two children. Seventy-five percent (n = 42) of parents reported they had heard of the HPV vaccine. Fewer fathers were aware of the HPV vaccine (58.3%; n = 14 vs.87.5%, n = 28; p = 0.01) than mothers. Among parents who had heard of the HPV vaccine (n = 42), 85.7% (n = 36) reported their children had received at least one dose of the HPV vaccine. Fewer fathers reported their child had been vaccinated against HPV (64.3%, n = 9 vs. 96.4%, n = 27; p = 0.06) than mothers. Moreover, 90% of parents (n = 18) whose children were unvaccinated reported willingness to vaccinate their adolescent children against HPV if recommended by their child’s physician. Findings indicate parents’ low to moderate awareness of the HPV vaccine, and high willingness to vaccinate their adolescent children if recommended by their child’s physician. Findings also demonstrate fathers’ lower awareness and acceptability of the HPV vaccine than mothers. Despite limitations and the need for more research, findings of this pilot study serve as a valuable first step toward building a knowledge foundation that is needed for developing future studies and interventions targeting Central American immigrant parents living in the US. Future studies can build on the findings of this exploratory study with other research designs and address its limitations by having a larger sample size and accounting for additional factors associated with Central American immigrant parents’ HPV awareness, knowledge, beliefs, attitudes, and vaccine acceptability from other communities across the US.

Opportunities to improve immune-based prevention of HPV-associated cancers

Immunization of adolescent girls with VLP vaccines, made of L1 proteins from the most medically significant high risk HPV types, is a major strategy for prevention of cervical cancer plus other HPV-associated cancers. Maximal population impact, including through herd immunity, requires high vaccination coverage. However, protection of unvaccinated women requires secondary prevention through cytology screening. Unfortunately in countries with the highest incidence/mortality due to cervical cancer HPV vaccination (or cytology screening) is not sufficiently available. Vaccination programme costs and a lack of accessibility of the populations for immunization remain significant hurdles. Several approaches could increase effective implementation of HPV vaccination. 1) Use of a single immunization of the current VLP vaccines. 2) Vaccination bundled with other paediatric vaccines with lower dosage to facilitate delivery, improve coverage and reduce costs through established logistics. 3) Local manufacture with lower cost systems (e.g. bacteria) for VLP or capsomer based vaccine production and utilization of additional protective epitopes (e.g L2) for increasing breadth of protection. However, all the latter need appropriate clinical validation. Gender neutral vaccination and extending routine vaccination strategies to women up to age 30 years in combination with at least one HPV screening test can also hasten impact on cancer incidence.

National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13-17 Years - United States, 2016.

The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents routinely receive tetanus, diphtheria, and acellular pertussis vaccine (Tdap), meningococcal conjugate vaccine (MenACWY), and human papillomavirus (HPV) vaccine (1) at age 11-12 years. ACIP also recommends catch-up vaccination with hepatitis B vaccine, measles, mumps, and rubella (MMR) vaccine, and varicella vaccine for adolescents who are not up to date with childhood vaccinations. ACIP recommends a booster dose of MenACWY at age 16 years (1). In December 2016, ACIP updated HPV vaccine recommendations to include a 2-dose schedule for immunocompetent adolescents initiating the vaccination series before their 15th birthday (2). To estimate adolescent vaccination coverage in the United States, CDC analyzed data from the 2016 National Immunization Survey-Teen (NIS-Teen) for 20,475 adolescents aged 13-17 years.* During 2015-2016, coverage increased for ≥1 dose of Tdap (from 86.4% to 88.0%) and for each HPV vaccine dose (from 56.1% to 60.4% for ≥1 dose). Among adolescents aged 17 years, coverage with ≥2 doses of MenACWY increased from 33.3% to 39.1%. In 2016, 43.4% of adolescents (49.5% of females; 37.5% of males) were up to date with the HPV vaccination series, applying the updated HPV vaccine recommendations retrospectively.† Coverage with ≥1 HPV vaccine dose varied by metropolitan statistical area (MSA) status and was lowest (50.4%) among adolescents living in non-MSA areas and highest (65.9%) among those living in MSA central cities.§ Adolescent vaccination coverage continues to improve overall; however, substantial opportunities exist to further increase HPV-associated cancer prevention.

HPV in West Virginia: Exploring Human Papilloma Virus Education, Prevention, and Beliefs

West Virginia has the highest incidence rate of cancers associated with Human Papilloma Virus (HPV) in the United States.1 This study explored issues that may provide some clues to the increased rate of HPV-associated cancers in West Virginia despite adequate vaccination coverage above the national average.2 Specific topics that were explored included knowledge of HPV and associated cancers, accessibility to preventative healthcare relating to HPV vaccination and Pap smear, as well as any cultural beliefs that may affect HPV-associated cancer prevention. A total of 1,038 State Fair attendees from 45 counties in West Virginia voluntarily consented to take a gender and knowledge specific survey. The results were analyzed and presented in graphical formats. The chi-squared test was used to test for significance of categorical variables. The results revealed an increased acceptance rate for HPV vaccination in the younger generations compared to the older age groups. The findings of this study suggest that a vigorous, all-inclusive educational campaign against HPV that details HPV-associated cancers, risk factors and mode of transmission, availability and safety of HPV vaccines, as well as preventative strategies, conducted by schools, clinics, and media may reduce the future incidence rate of cancers caused by HPV in West Virginia.

National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13-17 Years - United States, 2015.

The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents aged 11-12 years routinely receive vaccines to prevent diseases, including human papillomavirus (HPV)-associated cancers, pertussis, and meningococcal disease (1). To assess vaccination coverage among adolescents in the United States, CDC analyzed data collected regarding 21,875 adolescents through the 2015 National Immunization Survey-Teen (NIS-Teen).* During 2014-2015, coverage among adolescents aged 13-17 years increased for each HPV vaccine dose among males, including ≥1 HPV vaccine dose (from 41.7% to 49.8%), and increased modestly for ≥1 HPV vaccine dose among females (from 60.0% to 62.8%) and ≥1 quadrivalent meningococcal conjugate vaccine (MenACWY) dose (from 79.3% to 81.3%). Coverage with ≥1 HPV vaccine dose was higher among adolescents living in households below the poverty level, compared with adolescents in households at or above the poverty level.(†) HPV vaccination coverage (≥1, ≥2, or ≥3 doses) increased in 28 states/local areas among males and in seven states among females. Despite limited progress, HPV vaccination coverage remained lower than MenACWY and tetanus, diphtheria, and acellular pertussis vaccine (Tdap) coverage, indicating continued missed opportunities for HPV-associated cancer prevention.

426 cGMP production of a chimeric virus-like particle vaccine (RG1-VLP) for prevention of HPV-associated cancers

426 cGMP production of a chimeric virus-like particle vaccine (RG1-VLP) for prevention of HPV-associated cancers

Abstract 2367: cGMP production of a chimeric virus-like particle vaccine for prevention of HPV-associated cancers

Abstract The NCI Division of Cancer Prevention's PREVENT Cancer Preclinical Drug Development Program supports preclinical development and clinical translation of novel cancer preventive interventions. One of the projects currently supported came from principal investigators, Drs. Reinhard Kirnbauer and Richard Roden, who requested cGMP production of a novel chimeric virus-like particle (VLP)-based human papillomavirus (HPV) vaccine, comprising HPV16 L1 VLP with HPV16 L2-RG1 epitope repetitively displayed on the capsid surface (RG1-VLP). The vaccine is designed to prevent infection by a broad range of HPV types, including mucosal and cutaneous types not targeted by current vaccines (J Invest Dermatol 2013, 133:2706), and thus has the potential to become a broadly effective next generation HPV vaccine. The cGMP process is currently being developed and validated by Paragon Bioservices in Baltimore, MD, under NCI contract with MRIGlobal. RG1-VLP is expressed in Sf9 insect cells infected with a triple-plaque-purified recombinant baculovirus. After cell culture clarification and capsid maturation steps, VLPs are purified by a series of chromatography steps to remove host cell derived impurities. The purified VLPs are analyzed by ELISA and Western blot immunoassays. Removal of host cell protein and DNA is confirmed by ELISA and qPCR, respectively. Assembly of a chimeric RG1-VLP protein into full size VLP structures (approximately 50-60 nm in diameter) is verified by transmission electron microscopy. cGMP-produced VLPs should be available during the first half of 2016. The PREVENT Program will perform the required toxicology studies and will assist with IND filing, for a first-in-human Phase I study of RG1-VLP vaccine. While the clinical protocol is still under development, it is anticipated that 15-20 healthy adult volunteers will be enrolled into each of three to four escalating dose groups. While the primary objective of the Phase I study will be to establish the safety of RG1-VLP, preliminary immunogenicity studies will be included. Immunogenicity of RG1-VLP will be evaluated by serum anti-L1 and anti-RG1 antibody levels as well as protective and cross-neutralizing antibodies against HPV16 and a broad panel of HPV types including at least one type not covered by marketed vaccines. Citation Format: George W. Buchman, Brian P. Howard, Nadia Abdallah, Bala Medicherla, Mary Anne Fisher, Jonathan M. White, Michelle L. Kennedy, Shizuko Sei, Richard B.S. Roden, Christina Schellenbacher, Reinhard Kirnbauer, Robert H. Shoemaker. cGMP production of a chimeric virus-like particle vaccine for prevention of HPV-associated cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2367.

Abstract A57: Bug Your Doc: Get 3 shots! – A culturally appropriate social marketing intervention to increase HPV vaccination

Abstract HPV vaccination is recommended for all children ages 11-12, with catch up for females to age 26 and males to age 21, for prevention of HPV-associated cancers, which disproportionately affect African Americans. However, uptake of HPV vaccine has lagged far behind that of other adolescent vaccines recommended for the same ages (meningococcal and Tdap), and completion was lower among African Americans than whites until 2013. The purpose of this study was to pilot test a culturally-appropriate social marketing intervention targeting parents of African American pre-adolescents to increase initiation and completion of the 3-dose HPV vaccine series, using a community-engaged approach. A Community Advisory Board (CAB) and Teen and Parent Committee participated in the development of the intervention. While the messages were developed to be culturally-appropriate for African American parents based on formative research, the CAB wanted to ensure that the intervention was designed to be appropriate for use with families of diverse backgrounds. The goal of the “Bug Your Doc: Get 3 Shots!” social marketing intervention was to encourage parents to ask their child's doctor for all three pre-teen vaccines, including HPV vaccine, when they update their immunization record for 7th grade entry. This strategy aimed to “normalize” the HPV vaccine as just another routine vaccination for both boys and girls, rather than treating HPV vaccine as different. The messages focused on parents' desire to protect their children from harm (serious illnesses). Intervention materials included a short educational video, website (www.get3shots.org), promotional flyer, and refrigerator magnet. We used a two-group, delayed crossover design to pilot test the intervention materials with groups of parents in a workshop format, compared to a workshop on an unrelated topic. Participants were recruited through community-based organizations and university email listservs, and were able to attend the different workshops at the same location. We enrolled a convenience sample of 36 parents of 5th and 6th grade boys and girls (73% African American), of whom 29 completed two-month follow-up before crossover. Based on parent self-reports, very few children had already received any dose of the HPV vaccine at baseline, which was not significantly different between study arms (0% control, 12.5% intervention). By two month follow up, 43.8% of the parents in the intervention arm reported that they had obtained the HPV vaccine for their child, compared to no change in the control arm (0%). This difference was significant at p<.05, indicating a significant effect of the intervention on increasing HPV vaccine uptake. Qualitative feedback from parents also indicated that the parents liked the materials and found the information to be useful. These intervention materials could be used for parent/patient education in a variety of contexts, such as healthcare practices, schools, and community organizations, to improve parent knowledge and acceptability of the HPV vaccine as part of the adolescent vaccine platform and to increase vaccination. Increasing HPV vaccine uptake among African American adolescents will contribute to reducing disparities in incidence and mortality from HPV-related cancers. Citation Format: Pamela C. Hull, Elizabeth A. Williams, Dineo Khabele, Caree R. McAfee, Maureen Sanderson. Bug Your Doc: Get 3 shots! – A culturally appropriate social marketing intervention to increase HPV vaccination. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A57.

Human Papillomavirus (HPV) Infections and the Importance of HPV Vaccination.

HPV persistence is necessary for the development of anogenital cancer. Studies show that cervical and anal HPV infections in women and in men who have sex with men are common. Clearance of HPV infection is similarly common; few individuals show persistence unless they are HIV-infected. HIV strongly influences the development of cervical and anal cancer, as well as their pre-malignant counterparts. Women with cervical and vulvar HPV-associated lesions have higher rates of anal cancer than the general population. HPV also plays an important role in pathogenesis of head and neck cancers, particularly oropharyngeal cancer. Two commercially available HPV vaccines have been proven to be safe and efficacious against cervical HPV16/18 infections and associated precancerous lesions; one of these has also been shown to prevent HPV16/18-associated anal lesions. The FDA has also just approved a new nonavalent HPV vaccine. HPV vaccines will play an important role in prevention of HPV-associated cancers.

Prospects for prevention of HPV-driven oropharynx cancer

Prevention of HPV-associated cancers can take two forms-one through prevention of infection via prophylactic HPV vaccination, and one through interruption of disease progression through early identification (i.e.: screening) and treatment. Primary prevention via vaccination seems promising, as a proof-of-principal study demonstrated high vaccine efficacy against one-time detection of oral HPV16/18 infection. In addition to the direct benefit of vaccination, indirect protection from reduced genital HPV infection should also reduce oral HPV exposure at the individual level. Yet, for the current unvaccinated cohorts who will bear the burden of non-cervical HPV-associated cancers for the foreseeable future, no secondary prevention opportunities exist, as the field has not yet validated any screening methods for non-cervical HPV associated cancers. Serum HPV16 E6 antibody data suggest that this test might one day be able to detect many of the at-risk patients prior to tumor development. For any biomarker that proves valid and reliable, transitioning into clinical practice will require additional research focused on (1) diagnostics, (2) effective intervention, and (3) observed reductions in cancer mortality.

Human papillomavirus vaccine: Widening the scope for cancer prevention

Human papillomavirus (HPV) is the necessary cause of cervical cancer. The HPV oncoproteins E6 and E7 have crucial roles in various steps of carcinogenesis, inducing degradation of p53 and destabilization of pRb. Several clinical trials show that recombinant HPV vaccines are safe and effective in preventing persistent infection of HPV and associated anogenital lesions. Although most clinical studies to date have investigated the effectiveness of HPV vaccines in young female subjects, elderly females and males may also be candidates for HPV vaccines. Prophylactic HPV vaccination may be an ideal preventive method for other HPV-associated cancers in addition to cervical carcinoma. Carcinogenesis by HPV, efficacy trials of currently available HPV vaccines, and the possible roles of HPV vaccines in the prevention of HPV-associated cancers are reviewed in this article.

96/03638 Separation of Fischer-Tropsch catalyst/wax mixtures using dense-gas and liquid extraction

Prophylactic human papillomavirus (HPV) vaccines are recommended for prevention of HPV-associated cancers. Type-specific detection of HPV in formalin-fixed, paraffin-embedded (FFPE) tissues retrieved from diagnostic pathology laboratories is important in monitoring the impact of HPV vaccines. However, few typing assays have been validated for testing FFPE samples. Results of the Novaplex II HPV28 Detection (Novaplex) assay were compared with those from the reference assay (Linear Array with reflex Line Probe Assay) on 708 FFPE samples from cervical lesions. Novaplex showed high type-specific concordance with the reference method for HPV16/18, 9 types targeted by the Gardasil 9 vaccine, 14 high-risk types, and 21 types covered by comparison assays. The rate of inadequate samples was low in both approaches (reference, 3.4%; Novaplex, 1.7%). The proportion of discrepant types was less than 3.5% and positive concordance was greater than 75.0%. Furthermore, the type-specific positive agreement (92.0% to 98.0%), negative agreement (96.0% to 99.0%), and accuracy (97.0% to 99.0%) was high. Cohen's κ ranged from 0.86 to 0.89, indicating excellent agreement between Novaplex and reference assays. The results show that Novaplex is a suitable method for detection of HPV in FFPE tissues.