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HPV vaccines in Brazil and the world

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

The Human Papilloma Virus is the most common sexually transmitted infection worldwide. More than 200 different genotypes have been identified so far, and they are classified in five genera (Alpha, Beta, Gamma, Mu and Nu) [1]. Most of the infections caused by these types are transient and asymptomatic, since they are rapidly cleared by an intact immune system. However, HPV may cause clinical manifestations of variable severity. About 40 mucosal genotypes have been associated with the development of anogenital lesions [2]. These span from benign warts (condylomata), mainly caused by the low-risk HPV 6 and 11, to cancerous lesions, caused by high- risk (HR) types (e.g., HPV 16 and 18). Indeed, HR-HPV are implicated in the development of most cervical (close to 90% of the cases), anal (>80%), vulvar (around 40%), vaginal (around 70%), penile (around 50%) and oropharyngeal (13–56%) cancers. Because of the ascertained link between anal HPV infection and anal cancer development, and, in particularly, the increasing incidence of this neoplasia over the last years, the interest on the burden of anal HPV infection has been growing. Indeed, about 88% of anal cancer cases worldwide are associated with HPV infection 2. HPV 16 (75–80%) and HPV18 (about 3.5%) represent the most prevalent types in this neoplasia [3]. Most sexually active persons will have detectable HPV at least once in their lifetime [4]. The estimated incidence of HPV infection is high, with 14 million persons infected annually and 79 million persons with prevalent infection [5]. In the last years it emerged that in Italy the anogenital warts were more frequent (40,871 cases, 39.7% of the total) among other sexually transmitted diseases as latent syphilis (9190 cases, 8.9% of the total), bacterial cervicovaginitis (8798 cases, 8.5% of the total) and genital herpes (7860 cases, 7.6% of the total). In particular the anogenital warts were the most frequent pathologies among men (30,092 cases, 41.5% of total men) (http://www.iss.it/ccoa/index.php?lang=1&id=55&tipo=4). HPV-associated diseases include anogenital and other mucocutaneous warts as well as cervical, anal, vaginal, vulvar, penile and oropharyngeal cancer [1]. Anogenital warts (AGWs) (also known as genital warts, condylomata acuminata, condylomas) are benign proliferative lesions caused by human papillomavirus (HPV) types 6 and 11, which are found in >95% of lesions [1, 6]. AGWs are often co-infected with “‘high-risk” HPVs such as HPV 16–18. Genital warts are sexually transmitted, with transmission rates of about 60% between partners [7].

It is estimated that 79 million people in the US are currently infected with human papillomavirus (HPV). There are more than 200 different HPV types that are common worldwide. HPV types are categorized as either high risk (HR) or low risk (LR). LR types, such as HPV 6 and HPV 11, can cause genital warts or squamous papillomas of the oral cavity, while persistent infection with HR HPV types can induce cervical, anal, or head and neck cancers. Episomal HPV DNA can be detected in advanced stages of cancer. HPV integration in the host genome drives oncogenesis by the expression of the two major viral oncogenes, E6 and E7, which abrogate cell cycle checkpoints, promote cellular proliferation, and cause progressive genetic instability. Hence, screening for the presence of E6/E7 RNA transcripts expression is considered the gold standard for confirming active HPV infection. Early detection of active HPV is critical for better understanding of prognosis and therapeutics. So far, detection of integrated HPV DNA in tissue specimens has been challenging. A novel, cost-effective, in situ hybridization (ISH) detection assay has been developed using two sets of HPV probes with enhanced signaling, termed hyper probes. The Hyper HPV D probe detects HR HPV DNA and the Hyper HPV DR probe can simultaneously detect DNA and E6/E7 RNA of HR HPV subtypes in cancer cell lines and formalin fixed paraffin embedded (FFPE) biopsy specimens. The probes were tested on cervical carcinoma SiHa cells containing 1-3 copies of integrated DNA of HPV 16 and HPV negative cervical cancer C33A cell line. The Hyper HPV DR probe resulted in 1-3 puncta in more than 90% of SiHa cell nuclei, indicating integrated copies of HPV DNA into the host genome. There was also the additional presence of a diffuse signal which was abolished by pretreating SiHa cells with RNase. These data suggest the diffuse signal corresponds to E6/E7 mRNA expression. No signals were detected in HPV negative C33A cells. When cells were stained with Hyper HPV D probes, only punctate signals in nuclei of SiHa cells was present and no signal was evident in C33A control cells. Additionally, human cervical and anal FFPE biopsies were analyzed. Simultaneous presence of both punctate signals and diffuse signals were detected when using Hyper HPV DR probes in HR HPV infected tissues, while only punctate signal was detected when using HPV D hyper probes. The signal from the hyper probes was significantly stronger when compared to other commercially available HPV detection kits. Moreover, other commercially available kits failed to detect low copy of integrated HPV. In conclusion, these data demonstrate the Hyper HPV probes can reliably detect low copies of HPV DNA integrated in the host genome and the presence of HPV mRNA using ISH in HPV infected cells. Citation Format: Maurizio Mauro, Richard Delle Bovi, Jack Coleman. Sensitive detection of integrated HPV in carcinoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1401.

Human papillomavirus (HPV) is widespread known as the sexually transmitted infection, which is responsible, for genital warts and certain types of cancer. Low-risks HPV types are responsible for genital warts. Genital warts can be treated through various medical and surgical methods. High-risks HPV types may cause dangerous cancers such as cervical cancer. The clinical approach in treatment of HPV-related cancers were different depending on the diseases stage ranging from surveillance and minor procedures for dysplasia to chemotherapy for more advanced cases. It is crucial to vaccinate adolescents against HPV to prevent infections from high risk strains. Researchers have explored natural products as potential solutions against viral infections with eight biologically active compounds. Including EGCG, curcumin, podophyllotoxin, resveratrol, pterostilbene, tanshinone IIA, indole-3-carbinol, and carrageenan. They are showing promising therapeutic effects in treating different stages of HPV-related diseases. Clinical trials have demonstrated the effectiveness of EGCG and podophyllotoxin in treating warts while other compounds, like curcumin, resveratrol, pterostilbene, indole-3-carbinol, and tanshinone IIA offer benefits in combating cervical cancer. In addition, carrageenan shows promising effects in HPV transmission prevention. It appears that compounds from nature may have an impact, on different phases of the HPV infection like genital warts treatment, disease transmission prevention, and healing-related cancers. These findings highlight the potential of natural products as valuable sources to combat HPV infection and related cancers. Further more extensive studies are necessary to discover the effective mechanism of these natural compounds as anti-HPV agents.

Human Papillomaviruses (HPV) are small deoxy-ribonucleic acid (DNA) tumor viruses with an icosahedral virion structure associated with a wide spectrum of epithelial lesions, ranging from benign warts to invasive carcinomas. They have been difficult to study, in part because they have not yet been propagated in tissue culture. Fortunately, advances in molecular biology have allowed characterization of HPV genomes and identification of some HPV gene functions. In addition to their clinical importance, HPV represent an important tool for exploring virus-cell interactions, gene expression, cellular differentiation, and cancer. HPV infections are not only common, but also difficult to treat and prevent. Depending on the HPV type and location, the modes of HPV transmission may involve casual physical contact, sexual contact, and perinatal vertical transmission. HPV DNA genomes replicate at a low copy number in basal cells and, as most clinicians know, are difficult to eradicate. There is often a long latent period and subclinical infections, plus HPV DNA can be found in normal tissue adjacent to lesions. HPV can cause widely disseminated lesions, especially in the immuno-compromised host and in epidermodysplasia verruciformis (EV). In malignant lesions, HPV DNA is also found as fragments incorporated into the cellular genome. Unlike retroviruses such as Human Immunodeficiency Virus (HIV) that integrate into the cellular genome as part of their life cycle, HPV integration is a terminal event for viral replication. Such integration is critical, however, for viral-induced abnormal cell growth. Perhaps the most important implication of some ano-genital cancers is that they may be preventable. The data overwhelmingly suggests that avoidance of exposure to HPV, via abstinence or monogamy in both partners markedly reduces the risk of cervical cancer. A more realistic goal, however, is prevention of HPV transmission by the use of barrier method contraceptives, which may be protective against development of cervical carcinoma as reported byCripe (Pediatr Infect Dis J 9:836–844, 1990). Infection with HPV is the most common STD, afflicting approximately 80% of the population. HPV infection is an essential factor in cervical carcinogenesis and cervical carcinoma the second most common cause of cancer among women worldwide. In addition to cervical cancer, other malignancies in both men and women such as esophageal, oropharyngeal, and anal cancer have been causally associated with this virus. Other gender-specific HPV-related cancers include penile, vulvar, and vaginal cancer. Recent evidence also points to a possible role of other HPV infections in squamous cell carcinomas (SCC) of the skin. During the past 20 years, several types of HPV have been identified that cause specific types of cancers. The etiology of cancer of the cervix has been linked to several types of HPV, with a high preponderance of HPV-16. HPV-16 is the most common HPV type associated with a malignant phenotype regardless of organ of origin. HPV-16, together with HPV-18, accounts for approximately 70% of cervical cancers. Other non-oncogenic HPV types, including HPV types 6 and 11, are associated with over 90% of benign HPV-related lesions such as genital warts and juvenile respiratory papillomatosis as reported by Monk and Tewari (Gynecol Oncol 107:S6–S13, 2007).

Objective To determine the genotypes of human papillomavirus (HPV) and to estimate their correlations with recurrence of perianal and anal condyloma acuminatum (CA) among men who have sex with men (MSM) in Shanghai.Methods Tissue specimens were obtained from the lesions of perianal or anal CA in 57 MSM.Flow-through hybridization and gene chip were used to determine the genotypes of HPV in these specimens.Follow-up was carried out to observe the recurrence of CA in these patients after CO2 laser treatment.Results Of the 57 specimens,56 (98.2％) were positive for HPV,and a total of 11 HPV subtypes were identified.The predominant genotypes were HPV 11 (42 cases,75％ ) and HPV 6 (30 cases,53.6％),sequentially followed by HPV 16 (8 cases,14.3％),HPV 18 (4 cases,7.1％),HPV 33 (2 cases,3.6％),HPV 59(2 cases,3.6％),HPV cp8304 (2 cases,3.6％),HPV 31 (1 case,1.8％) and HPV 35 (1 case,1.8％).Of the HPV-positive specimens,64.3％ (36/56) harbored low risk HPV types (11 and/or 6),and 35.7 ％ (20/56) harbored high risk HPV types.Among the 20 specimens positive for high risk HPV,17 (85％) harbored both low risk- and high risk-HPV genotypes.During the 6-month follow-up after CO2 laser treatment,recurrence was observed in 95％ of patients with high risk HPV and 66.7％ of patients with low risk HPV (P ＜ 0.05).Conclusions Among MSM with perianal and anal CA in Shanghai,the predominant genotypes of HPV are low risk types 11 and 6; high risk HPV infection is usually complicated by low risk HPV infection; the recurrence of CA is higher in patients with high risk HPV than in those with low risk HPV. Key words: Condylomata acuminata; Human papillomavirus; Homosexuality; Male

To assess attitude and knowledge among parents or guardians of 12-year-old girls about human papillomavirus (HPV), cervical cancer, and HPV vaccination. Material andMethods: A mail survey was sent to a randomized sample of 1,000 parents or guardians of 12-year-old girls from a cohort of total 2,092 girls born in 1995 and registered in the Icelandic National Register by the end of December 2007. Of the 994 eligible parents, 583 (59%) returned the questionnaire. Majority of the respondents were mothers who had two or three children. More than one-third of respondents had university education and 84% were married or living with a partner. Over two-thirds did not know that HPV causes cervical cancer and genital warts. Almost all (> 90%) would vaccinate theirs daughters with a HPV vaccine, 73% said they would vaccinate their sons, or themselves if the vaccine was effective for them. Only 11% believed HPV vaccination would increase promiscuity or decrease cervical screening attendance. In Iceland, willingness to vaccinate young girls with HPV vaccine is high, however, knowledge about HPV infections is limited.

Book Review: Prophylaxis and Early Detection of HPV-Related Neoplasia, Herbert Pfister, Editor

Immune Response 2019 : Factors influencing intention to obtain the HPV vaccine among a population of universitywomen in morocco - Dr. Aicha yacouti â University of Hassan

Background Introduction: Genital warts or condyloma accuminata - are raised lesions that develop on the skin and mucous membranes due to infection with some types of human papillomavirus (HPV). Human papillomavirus infection is one of the most common sexually transmitted diseases and it is detected at least once in the lifetime of most sexually active people. Despite various treatment options currently available, many patients experience persistent and refractory disease. We sought to evaluate the clinical effectiveness and safety profile of intralesional quadrivalent HPV vaccine (Gardasil) for the treatment of genital warts. Aim of the Work This study aimed to evaluate the clinical efficacy of intralesional quadrivalent Human Papilloma Virus vaccine in the treatment of genital warts and assess its impact on serum and tissue IFNγ before and after treatment. Patients and Methods This study included 10 female patients with ano genital warts. They received intralesional gardasil, (0.3 ml) one injection session every 2 weeks for maximum 4 injection sessions. All the patients were recruited from the Dermatology, venerology outpatient clinic at El Houd el Marsoud Hospital during the period From May 2022 to August 2022. The lab part of the study was done at clinical pathology departement at Ain Shams University. All patients were subjected to clinical examination, photographic examination at first visit before any treatment and at each follow up visit, follow-up of patients were carried out at two-week intervals for 3 months to assess clinical response and complication(s) of injection. IFN-γ was asseyed by enzyme-linked immunosorbent assay (ELISA) using human IFN-γ ELISA Kit. Then quantitative determination of human IFN-γ concentrations were recorded. Results There was a highly significant decrease in the median number of lesions throughout the different sessions as compared to the baseline. The median number of lesions decreased from 14 at the baseline to 12, 10, 8 and 4 at the 2nd, 3rd, 4th sessions and last visit respectively. There was significant decrease in size of the largest injected wart after each treatment session compared to base line. The median size decreased from 1.25 cm at the baseline to 0.4, 0.2, 0.2 and 0.1 cm at the 2nd, 3rd, 4th sessions and last visit respectively. Conclusion the current study showed that intralesional HPV vaccine (gardasil) is an effective treatment modality in treatment of genital warts. INF-γ is considerd a good indicator factor for immune mechanisms needed for wart clearance.

Human Papillomavirus Genotypes and Anal-Related Lesions Among HIV-1-Infected Men in Milan, Italy

BackgroundDespite the high prevalences of Human Papilloma Virus (HPV) infections and cervical cancer in Nigeria, utilization of the HPV vaccine as a highly effective preventive measure remains low. The aim of this study was to find out the awareness and attitudes of caregivers to HPV infections and the factors that determine acceptance of an HPV vaccine for their pre-adolescent girls.MethodsThis was a cross-sectional descriptive study of 508 caregivers of female children in Enugu Nigeria. A semi-structured questionnaire was used to collect information on knowledge of HPV, cervical cancer as well HPV vaccine and its acceptance for pre-adolescent female children. The data was analysed using descriptive statistics.ResultsFive hundred and eight (508) caregivers of female children were interviewed. Less than half, 221,(43.5%) of them knew about HPV, among these, 163 knew how HPV is transmitted. Only 12 (2.4%) of the caregivers know that an HPV infection is a major risk factor for cervical cancer. Among the 221 participants who knew the meaning of HPV, 132 (59.7%) were aware of an HPV vaccine. Only 26 (19.7%) of those aware of a vaccine agreed it can effectively prevent cervical cancer. Lack of awareness about the vaccine and accessibility were the major reasons given by parents on why the vaccine has not been received by their female children.ConclusionDespite high levels of education, awareness of HPV, HPV vaccine and the risks for cervical cancer remains low among caregivers in Enugu, south-east, Nigeria. Awareness and accessibility were the major determinants of HPV vaccine uptake among the caregivers. There is a need for massive and sustained awareness creation to increase HPV vaccination uptake in Nigeria.

Objective To measure the effect on genital warts of the national human papillomavirus vaccination programme in Australia, which started in mid-2007.Design Trend analysis of national surveillance data.Setting Data collated from...

In theory, recognition that a pandemic infection is responsible for more than half a million cancer cases each year would attract huge media attention, and infection control would become the subject of preventative efforts from all global health agencies. Media attention would likely be particularly acute if the majority of deaths was among women rearing families in the developing world and if the disease were sexually transmitted. A vaccine capable of preventing the disease would be diligently pursued and, once available, promptly distributed for the health and welfare of humankind. Human papillomavirus (HPV) infection fits this scenario; however, HPV has yet to make an impact on either the media or public thinking as outlined in the previous paragraph, even though the link between HPV infection and cervical cancer has been recognized for more than 20 years. It is possible that the delay between acquisition of HPV infection and death, on average 20 years, or the asymptomatic nature of acute infection, greatly diminishes the immediacy of the public impact of this epidemic. Although apparently safe vaccines capable of preventing 90% of HPV infections are in the offing, focus on prevention of HPV associated deaths is being diverted by debates about the morality of vaccination against a sexually transmitted infection and its hypothesized impact on human sexual behavior. A roundtable discussion was held in Vancouver, British Columbia to consider and develop a consensus statement among informed clinicians about HPV infection, the role of HPV in cervical cancer, the role of HPV in other anogenital malignancies, the role of HPV in genital warts and the prospects for control of the global HPV pandemic through vaccination. The consensus statements outlined within have been agreed upon and represent the informed opinions of this expert working group.