Risk Human Papillomavirus Types Research Articles

Cervical cancer in Thailand: 2023 update.

Cervical cancer continues to pose a challenge to the health of Thai women, as the second most common cancer after breast cancer. Since high-risk human papillomavirus (HPV) types are the main cause for cervical cancer, cervical cancer screening and HPV vaccination are necessary to reduce the incidence of this disease. At present, the World Health Organization hopes to reduce the incidence of cervical cancer to 4 or less cases per 100,000 women-years using 90%- 70%-90% intervention by 2030. The first intervention involves vaccinating 90% of women aged 15 years with the HPV vaccine. The second intervention involves screening 70% of women between the ages of 35 and 45 years using a high-performance screening test. The third intervention involves detecting cervical lesions in 90% of affected women to enable diagnosis and treatment. In this context, this study reviews trends in the incidence and mortality rates of cervical cancer in Thailand, in addition to providing an up-to-date overview of the causes and necessary risk factors for cervical cancer, as well as reporting on cervical screening and HPV vaccination rates and cervical cancer during the coronavirus disease 2019 (COVID-19) pandemic. This study may prove useful for the formulation of policy aimed at eliminating cervical cancer in Thailand, such as the implementation of a free HPV vaccine service and providing athome kits for cervical screening through clinics and pharmacies. In addition, this review also highlights the need for further research on the effects of the COVID-19 pandemic on cervical cancer screening rates in Thailand.

Feasibility and Acceptability of Self-sampling for Human Papillomavirus DNA Testing Among Asymptomatic Women in Rural Delta State, Nigeria

Background: Self-sampling and human papillomavirus (HPV) DNA testing can be vital tools in cervical cancer screening for hard-to-reach women with limited access to health care in sub-Saharan Africa. This study explored the feasibility and acceptability of self-sampling for HPV testing among asymptomatic women in Orhuwhorun community in Delta State. Methods: This was a cross-sectional study of 230 women aged between 30 - 65years, enrolled by a multi-stage sampling method. Recruited women were asked to provide self-collected vaginal samples between May and June, 2021. HPV detection and genotyping was done using 21 HPV Geno-Array Diagnostic kit. Participants were asked to complete questionnaires after self-sampling to point out their experiences and acceptability of HPV self-sampling. Results: An excellent feasibility of self-sampling (95.2%) was observed. The acceptability rate of self-sampling was 93.0%, and 99.6% (229/230) of the participants were confident that they used the device correctly. The quality of self-sampling was satisfactory in 100% of the samples; 21.1% (48/228) of the samples were positive for HPV, including 12.3% (28/228) with high-risk HPV types,2.6% (6/228) with probable high risk HPV types and 1.8% (4/228)with low-risk HPV types. Multiple HPV infection occurred in 10 cases (4.4%). Conclusion: This study indicates that self-sampling is a feasible and acceptable approach for cervical cancer screening among women in rural Delta State. Thus, the government should consider self-sampling as a valuable strategy in implementing national cancer screening programme.

The distribution of HPV subtype in vulvar intraepithelial neoplasia and the association with recurrent VIN and vulva cancer in Taiwan.

e17635 Background: Vulvar intraepithelial neoplasia (VIN) is a precursor lesion of vulvar cancer. Human papillomavirus (HPV) is causative for part of VIN lesions. This retrospective study aimed to investigate HPV distribution in patients with vulvar intraepithelial neoplasia (VIN) and the factor associated with the recurrence of high-grade vulvar intraepithelial neoplasia (VIN2+), high-grade vaginal intraepithelial neoplasia (VAIN) , cervical intraepithelial neoplasia(CIN) or progression to vulvar cancer. Methods: We retrospectively analyzed patients who diagnosed as vulvar squamous intraepithelial lesions between 1990 and 2014 in our institution. All the diagnoses and classifications were confirmed by two pathologists in 2015 ISSVD terminology. HPV DNA was extracted from formalin-fixed and paraffin-embedded samples. SPF1/GP6+ polymerase chain reaction (PCR) followed by HPV Blot and E6 type-specific PCR were performed. Results: Ninety-eight VIN patients were included in our analysis. Ninety-three percent were positive for HPV and HPV16 (43.9%), HPV6 (11.38%), HPV11 (8.94%), and HPV58 (4.88%) were the most prevalent types. Patients with positive HPV were diagnosed younger than those with negative results (43.0 years vs. 61.1 years, P = 0.049). In 15 patients who with recurrent VIN (n = 11) or progression to vulvar cancer (n = 4), had positive HPV. All 4 patients who had progression to cancer were positive for HPV16 in their initial VINs. High risk type HPV infection, positive HPV16, and positive alpha-9 types are significant risk factors for recurrent VIN and progression to cancer. Conclusions: Positive HPV was detected in 92.8% of VINs and was related to younger age at diagnosis. HPV16 was the most prevalent type and was significantly related to recurrence/ progression. Other significant risk factors for recurrent VIN or progression to cancer were high-risk HPV and alpha-9 types. Closely monitor of those patients with risk factors was indicated for early detection and treatment of recurrent VIN and vulvar cancer.

Human papillomavirus vaccine

Cervical cancer is the fourth most common cancer in women worldwide and is a significant public health problem. Currently, there are three bivalent human papillomavirus (HPV) vaccines targeting high-risk HPV types (16, 18), two quadrivalent vaccines targeting two high risk HPV types (16,18) and two low risk types (6,11) and one nonavalent vaccine against HPV 16,18, 31, 33, 45, 52, 58, 6 and 11. All are WHO approved vaccines and show excellent seropositivity (>95%) even at 5–10 years' post-vaccination irrespective of dosing schedule. These vaccines are relatively safe with minor local side effects. The WHO recommends two dosage vaccination schedule for girls aged 9–14 years with an off-label recommendation for a single-dose schedule. HPV vaccination has shown efficacy against the reduction of cervical intraepithelial neoplasia, invasive cervical cancer, anogenital warts and vulvovaginal intraepithelial neoplasia in numerous population/registry-based cohort studies worldwide. Countries such as Australia and Sweden where vaccination began as early as 2006–2008 have seen a major reduction in the incidence of cervical cancer in the vaccinated cohorts. Model based projection studies have also indicated significant vaccine efficacy with two doses and single dose in catch-up programmes. In this article, we provide an update on the vaccine recommendations, immunogenicity and efficacy data derived from registry-based cohort studies and trials published mostly in the last 5 years.

Genital Human Papillomavirus Infection in women from Florianópolis - Santa Catarina, Brazil

Introduction: Human Papillomavirus (HPV) infection is the most common sexually transmitted infection in women. About 80% of sexually active women will have contact with this virus at some age in their lives. Most infections will be transient, but when the infection becomes persistent, associated with high oncogenic risk HPV, there may be progression to cancer, especially cervical cancer. The best way to prevent HPV infection is through the use of vaccines. Objective: To assess which are the most prevalent types of HPV in the city of Florianópolis, Brazil and if the majority of the diagnosed types are contained in the HPV vaccines currently available on the market and in the public health sector. Methods: More than 14,727 HPV tests were evaluated for the diagnosis of genital HPV infection in women from Florianópolis. The prevalence of infection was evaluated according to age of the women. HPV detection was performed using molecular biology tests, such as hybrid capture (for diagnosis of the HPV group, high or low oncogenic risk) and PCR (viral genotyping) techniques. Results: The diagnosis of HPV infection was made for women between one and 102 years of age. The highest positivity of the exams was observed in women aged 20–25 years (51% of the exams). The most prevalent age group was 31–35 years old (23.5%), and the lowest was for women aged 70 and above (0.6%). High oncogenic risk HPV was detected in 94.1% of positive samples and was the most frequent in all age groups. Mixed infection (high- and low-risk HPV) was more prevalent in the 66–70 age group (25.6%). The most frequent genotypes were non-16/18 high oncogenic risk HPV (77% of positive cases). HPV 16 was found in 17.1% of positive cases, and HPV 18 in 6.5%. Conclusion: The most prevalent types of HPV in Florianópolis in the last 6 years are non-16/18 high oncogenic risk HPV types, viral types not covered by the current HPV vaccine available in the public health sector in Brazil.

Hookworm infection associates with a vaginal Type 1/Type 2 immune signature and increased HPV load.

Helminth infection-driven changes to immunity in the female reproductive tract (FRT) is an immune axis that is currently understudied but can have major implications for the control of FRT infections. Here we address how human hookworm infection associates with vaginal immune profile and risk of Human papillomavirus (HPV) infection. Stool, blood, cervical swabs and vaginal flushes were collected from women from the Central region of Togo to screen for hookworms (Ancylostoma duodenale) and high carcinogenic risk HPV types, via Kato Katz and PCR, respectively. Cytokine, chemokine and immunoglobulin levels were analysed in cervicovaginal lavages and plasma samples. A pronounced mixed Type 1/Type 2 immune response was detected in the vaginal fluids of women with hookworm infection and this immune signature was a notable feature in hookworm-HPV co-infected women. Moreover, hookworm infection is positively associated with increased risk and load of HPV infection. These findings highlight helminth infection as a significant risk factor for acquiring a sexually transmitted viral infection and potentially raising the risk of subsequent pathology.

Configuration of the surfaces of epithelial cells infected by human papillomavirus

Human papillomavirus (HPV) types were investigated hy iri situ hybridization (ISH) in biopsiesfroin J8patients with diverse pathologies ofcervix uteri (7 condylomas, 1 CINI +HPV, 3 CIN II, 4 CIN II + HPV and 3 CIN III). Cervical sniears ofthe same patients were processed by Scanning Electron Mycroscopy (SEM) in order to study the configuration of sitrfaces ofcells infected hy different HPV types. Seven condylomas, I CIN I + HPV, 3 CIN II and 3 CIN II + HPV showed alinost identical surface configurations to those of normal cells (short, thin, homogeneous microvi lli o r typicai microridgesj. This group presented low, moderate and high risk HPV types in a episomal form, while I CINII + HPV and3 CINIII with integratedHPV 16/]8 exfoliatedcells covered with gross microvilli, with variahle length and uneven distribution, oran amorphous surface. The presence of HPV 16/18 cannot be sufficient for the development of an anormal configuration, hut the integrated State ofthis viral type coiild he related to the morphological changes in cellular surface morphology. The results of this paper underline the importance of viral integration in the genesis of cervical carcinoma.

A Retrospective Study of Verruca

Background: Verruca (non genital warts) is a quite common public health problem caused by viral infection of low risk Human Papilloma Virus (HPV) types, risking patients of all backgrounds. There is still no ideal treatment for verruca with little knowledge regarding the effectiveness of the available therapies, which results in the lack of therapeutic standard for patients. Purpose: To evaluate the incidence, management, and effectiveness of verruca treatment. Methods: This was a descriptive, retrospective study with a cross-sectional design. All patients diagnosed with verruca in Tumor and Skin Surgery Division of the Dermatology and Venereology Outpatient Unit at Dr. Soetomo General Academic Hospital Surabaya between January 2016 and December 2020 were included in the study. Result: The results of this study obtained a total of 113 verruca patients, consisting of 61 (53.98%) male patients and 52 (46.01%) female patients, mostly aged 20-60 years old (45 patients [39.82%]). The upper extremity was the most common location where the lesion was found (39 patients [34.5%]). Electrosurgery was the most performed method (38 patients [33.6%]). Thirty-one patients who were treated and returned to the clinic at least once during the month were evaluated for the resolution of the lesion after undergoing therapy. Among 31 patients, resolution was reported in 35.5% of cases. Conclusion: Verruca is a common condition in general practice with many treatment options available yet often neglected. Knowing the available evidence for efficacy of those treatments is critical for dermatologist when considering treatment and educate patients.

Mathematical Modeling and Computational Prediction of High-Risk Types of Human Papillomaviruses.

Cervical cancer is one of the main causes of cancer death all over the world. Most diseases such as cervical epithelial atypical hyperplasia and invasive cervical cancer are closely related to the continuous infection of high-risk types of human papillomavirus. Therefore, the high-risk types of human papillomavirus are the key to the prevention and treatment of cervical cancer. With the accumulation of high-throughput and clinical data, the use of systematic and quantitative methods for mathematical modeling and computational prediction has become more and more important. This paper summarizes the mathematical models and prediction methods of the risk types of human papillomavirus, especially around the key steps such as feature extraction, feature selection, and prediction algorithms. We summarized and discussed the advantages and disadvantages of existing algorithms, which provides a theoretical basis for follow-up research.

HPV and HIV Coinfection in Women from a Southeast Region of Romania-PICOPIV Study.

Background and Objectives: Romania faces one of the highest cervical cancer burdens in Europe though it is a preventable cancer through population screening by cytology and human papillomavirus (HPV) detection. Also, it has one of the highest incidences of human immunodeficiency virus (HIV) infection. HPV and HIV coinfection are frequently encountered. The aim of study was to establish the prevalence of HPV infection among HIV-positive women in Southeast Region of Romania, to genotype high risk HPV types -and to correlate the results with clinical data and cytological cervical lesions. Materials and Methods: 40 HIV-positive women were screened for HPV types and for cytological cervical lesions. The findings were evaluated in correlation with CD4 cell counts, HIV viral load, age at first sexual intercourse, number of sexual partners, vaginal candidiasis, and Gardnerella using statistical methods. Results: 19/40 (47.5%) women were positive for HPV types, 63.15% infected with single HPV type and 36.85% with multiple HPV types. The most frequent types were type: 31 (42.1%), 56 (31.57%), 53 (15.78%). On cytology, 34 (85%) women were found with NILM of which 38.23% were HPV-positive. Fifteen percent of women had abnormal cytology (three ASC-US, three LSIL), and all of them were HPV-positive. Through analyzing the value of CD4 count, women with CD4 count ≤ 200 cells/μL were found to be significantly more likely to be infected with HPV; meanwhile there was no correlation between the detection of HPV types and HIV viral load. Candida or Gardnerella were more often associated with HIV-positive women with HPV, than in women without HPV. Conclusions: Infection with HPV types is common among HIV-positive women in the Southeast Region of Romania and it is associated with age at the beginning of sexual life, number of sexual partners, CD4 value, vaginal candidiasis, and Gardnerella infection.

National experience in the first two years of primary human papillomavirus (HPV) cervical screening in an HPV vaccinated population in Australia: observational study.

ObjectiveTo review the first two years of the primary human papillomavirus (HPV) cervical screening programme in an HPV vaccinated population.DesignObservational study.SettingAustralia.Participants3 745 318 women with a primary HPV test between 1 December 2017 and 31 December 2019; most women aged <40 years had previously been offered vaccination against HPV16 and HPV18.InterventionsPrimary HPV screening with referral if HPV16 or HPV18 (HPV16/18) positive and triage with liquid based cytology testing (threshold atypical squamous cells-cannot exclude high grade squamous intraepithelial lesion) for women who were positive for high risk HPV types other than 16/18. A 12 month follow-up HPV test was recommended in triaged women with a negative or low grade cytology result, with referral if they tested positive for any high risk HPV type at follow-up.Main outcome measuresProportion of women who had attended for their first HPV screening test, tested positive, and were referred for colposcopy; and short term risk of detecting cervical intraepithelial neoplasia (CIN) grade 2 or worse, CIN grade 3 or worse, or cancer.Results54.6% (n=3 507 281) of an estimated 6 428 677 eligible women aged 25-69 had undergone their first HPV test by the end of 2019. Among those attending for routine screening, positivity for HPV16/18 and for HPV types not 16/18 was, respectively, 2.0% and 6.6% in women aged 25-69 (n=3 045 844) and 2.2% and 13.3% in highly vaccinated cohorts of women aged 25-34 (n=768 362). Colposcopy referral (ages 25-69 years) was 3.5%, increasing to an estimated 6.2% after accounting for women who had not yet had a 12 month repeat test. Cervical cancer was detected in 0.98% (456/46 330) of women positive for HPV16/18 at baseline, including 0.32% (89/28 003) of women with HPV16/18 and negative cytology. Women with HPV types not 16/18 and negative or low grade cytology at both baseline and 12 months were at low risk of serious disease (3.4% CIN grade 3 or worse; 0.02% cancer; n=20 019) but estimated to account for 62.0% of referrals for this screening algorithm.ConclusionsColposcopy referral thresholds need to consider underlying cancer risk; on this basis, women with HPV16/18 in the first round of HPV screening were found to be at higher risk regardless of cytology result, even in a previously well screened population. Women with HPV types not 16/18 and negative or low grade cytology showed a low risk of serious abnormalities but constitute most referrals and could be managed safely with two rounds of repeat HPV testing rather than one. HPV16/18 driven referrals were low in HPV vaccinated cohorts.

HPV-related quality of life in diagnosed women: A longitudinal study.

This paper explored changes in the HPV-related quality of life (QoL) of 209 women diagnosed with human papillomavirus (HPV) during 1 year of medical monitoring, at three time points (6-month interval between them). Participants completed the HPV Impact Profile (HIP) questionnaire to assess HPV-related QoL. The relationship between HIP scores and time was moderated by the HPV risk type and infection duration: an HPV diagnosis had a stronger negative effect on patients with an HPV high-risk type and on those living with HPV for a long period of time. Age, condom use, motherhood, and type of family were significant predictors.

Detecting Human Papillomavirus Type 16 in Cervical Cancer Patients with Molecular Variation of Gene L1 in Riau Province Indonesia.

Background:Cervical cancer is the second most deadly cancer in the world after breast cancer. The cancer is caused by infection of high risk Human Papillomavirus (HPV) type 16. It is often found in cervical cancer of which the genome structure is composed of L1 proteins. The L1 protein makes up the viral capsid that has an important role in causing the cervical epithelium. Several studies have found the differences in HPV nucleotides variants that lead to changes in amino acids that disrupt the structure, the natural function of the virus itself, and ultimately lead to changes in biological functions including host immunological recognition. Variation of the L1 gene also affects the effectiveness of existing vaccines. Methods:This research was a descriptive study conducted at the laboratory of microbiology, the Faculty of Medicine, Universitas Riau, Pekanbaru from February to August 2018. The study was aimed at looking at the molecular variations of the L1 HPV type 16 gene and examining phylogenic kinship. Results:The SNPs (Single Nucleotide Polymorphism) which occurred in 26 sample isolates are the substitution of C/G (6240), A/G (6432), T/G (6686), C/T (6824). These variations also cause changes in amino acids, insertion of ATC nucleotide bases (6902), and deletions of GAT bases (6954). Conclusion:There are molecular variations of the L1 HPV type 16 gene which can cause different host immune responses. Phylogenic kinship of HPV type 16 isolate in Riau is similar to Asian-American isolate.

Genital infection by Human papillomavirus (HPV) in women from Santa Catarina/Brazil

Introduction: Human Papillomavirus (HPV) infection is the most common sexually transmitted infection in women. About 80% of sexually active women will have contact with this virus at some point in their lives. Most infections will be transient, but when the infection becomes persistent and associated with a high oncogenic risk of Human Papillomavirus, there may be progression to cancer, especially cervical cancer. The best way to prevent Human Papillomavirus infection is through the use of vaccines, which have been available to the public in Brazil since 2014. Objective: This study aimed to assess the most prevalent types of Human Papillomavirus in the state of Santa Catarina, Brazil, and its mesoregions and if the majority of diagnosed types are contained in the Human Papillomavirus vaccines currently available on the market. Methods: A total of 20,000 Human Papillomavirus tests were evaluated for the diagnosis of genital Human Papillomavirus infection in women from the state of Santa Catarina, Brazil. The prevalence of infection was evaluated according to age and the city of origin of the exams. Human Papillomavirus detection was performed using molecular biology tests, such as hybrid capture (for diagnosis of the Human Papillomavirus group, high or low oncogenic risk) and polymerase chain reaction (viral genotyping) techniques. Results: The diagnosis of Human Papillomavirus infection was performed on women between 1 and 102 years of age. The age with the highest Human Papillomavirus positivity, as expected, was 20–25 years (45.6%) and the lowest after 70 years (7.1%). The highest Human Papillomavirus positivity of the exams was observed in the Serrana region of Santa Catarina state (58.9% of the exams). A high-oncogenic-risk Human Papillomavirus was detected in 93% of positive samples and was the most frequent in all age groups. Mixed infection (high- and low-risk Human Papillomavirus) was more prevalent in the 66–70 age group (29.3%) and in the Southern Region of Santa Catarina (26.4%). The most frequent genotypes in the state of Santa Catarina were non-16/18 high oncogenic risk Human Papillomavirus (76.9% of positive cases). Human Papillomavirus 16 was found in 17.1% of positive cases and Human Papillomavirus 18 in 6.6%. Conclusion: The most prevalent types of Human Papillomavirus in the state of Santa Catarina in the past 6 years are the non-16/18 high oncogenic risk Human Papillomavirus types, which are viral types not covered by the current Human Papillomavirus vaccines available in Brazil.

Correlation of the ALA-PDT Treatment Efficacy and the HPV Genotype Profile of Genital Warts after Cryotherapy Failure and Podophyllotoxin Therapy in Male Patients.

Background: Genital warts are the manifestation of the human papillomavirus (HPV) infection, which may last for weeks or months before the clinical presentation. The primary aim of the study was the correlation of the DNA HPV genotypes eradication with the treatment response in male patients with persistent genital warts. Methods: Twenty-one male patients (age range: 22–58) after failure of cryotherapy and podophyllotoxin treatment were enrolled in the study. Genetic tests (Real Time - PCR method) analyzed the presence of DNA-HPV before and 6 months after four sessions (4 weeks apart) of photodynamic therapy with 5-aminolaevulinic acid (ALA-PDT). The treatment efficacy was evaluated before each PDT session and at the end of the study. Results: The single HPV DNA type was present in 15/21 of the patients (13/15 HPV6). The high-risk HPV types were found in 8/21 subjects, of which 6/8 had several types. Six months after four sessions of PDT, complete response was found in 16/21 (76.19%; p = 0.0007) of patients, and DNA HPV clearance was found in 66.67% (p = 0.03). The eradication rate differed among patients with primary low-risk and high-risk HPV types—76.92% (10/13; p = 0.0003) and 50% (4/8; p = 0.05) respectively. Conclusion: ALA-PDT is an effective treatment even after the failure of previous modalities. The persistence of clinical lesions and high oncological risk HPV types should be an indication for treatment prolongation.

Human Papilloma Virus Types 16/18 Distribution in Invasive Cervical Cancer: An Evidence for Vaccination in Bihar, India

There is high incidence of cervical cancer in Bihar, India. Vaccination for cervical cancer in developed countries has played a crucial role in limiting the incidence rate of cervical cancer worldwide. In consideration of debate on clinical efficacy of Human Papilloma Virus (HPV) vaccine in India, study on the prevalence of high risk HPV 16/18 strains in different regions of the nation becomes very crucial. Few individual states have started vaccination but centralised vaccination program does not exist due to lack of sufficient genotypic study of Human Papilloma Virus in different parts of India. Bihar is the third most populous state of India and HPV 16/18 distribution has not been reported yet. The nationwide data of HPV 16/18will help to develop a unified centralised vaccination program. We carried out a distribution study of high risk HPV type 16 and 18 in cervical cancer patients attending a tertiary care hospital of Bihar, India.HPV 16/18 types were analysed in cervical cancer tissues (n = 96) of patients attending the regional cancer hospital of Bihar. Tissue samples were analysed for HPV 16 and HPV 18 using a Real Time PCR technique. The results suggest very high prevalence of HPV 16/18. HPV was identified in all the samples (96/96). About, 74 (77.08%) samples presented with HPV 16 whereas, 16 (16.67%) of the samples presented with HPV 18. 6 Co-infection was presented in 6 (6.25%) of the samples of cervical cancer tissues. HPV 16/18 prevalence is more in the women aged between 41 to 61 years.We report 100% prevalence of HPV16/18 in the cervical cancer tissue samples. A way to minimise this gynaecological concern would be to introduce prophylactic vaccines and early screening in the state of Bihar. The data generated would be crucial in drafting for community screening of HPV. We strongly emphasize the prophylactic HPV Vaccination against HPV 16 to control the alarming rate of cervical cancer in one of the most populous state of India, Bihar.

Intrabodies targeting human papillomavirus 16 E6 and E7 oncoproteins for therapy of established HPV-associated tumors

BackgroundThe oncogenic activity of the high risk human papillomavirus type 16 (HPV16) is fully dependent on the E6 and E7 viral oncoproteins produced during viral infection. The oncoproteins interfere with cellular homeostasis by promoting proliferation, inhibiting apoptosis and blocking epithelial differentiation, driving the infected cells towards neoplastic progression. The causal relationship between expression of E6/E7 and cellular transformation allows inhibiting the oncogenic process by hindering the activity of the two oncoproteins. We previously developed and characterized some antibodies in single-chain format (scFvs) against the HPV16 E6 and E7 proteins, and demonstrated both in vitro and in vivo their antitumor activity consisting of protective efficacy against tumor progression of HPV16-positive cells.MethodsEnvisioning clinical application of the best characterized anti-HPV16 E6 and –HPV16 E7 scFvs, we verified their activity in the therapeutic setting, on already implanted tumors. Recombinant plasmids expressing the anti-HPV16 E6 scFvI7 with nuclear targeting sequence, or the anti-HPV16 E7 scFv43M2 with endoplasmic reticulum targeting sequence were delivered by injection followed by electroporation to three different preclinical models using C57/BL6 mice, and their effect on tumor growth was investigated. In the first model, the HPV16+ TC-1 Luc cells were used to implant tumors in mice, and tumor growth was measured by luciferase activity; in the second model, a fourfold number of TC-1 cells was used to obtain more aggressively growing tumors; in the third model, the HPV16+ C3 cells where used to rise tumors in mice. To highlight the scFv possible mechanism of action, H&E and caspase-3 staining of tumor section were performed.ResultsWe showed that both the anti-HPV16 E6 and HPV16 E7 scFvs tested were efficacious in delaying tumor progression in the three experimental models and that their antitumor activity seems to rely on driving tumor cells towards the apoptotic pathway.ConclusionBased on our study, two scFvs have been identified that could represent a safe and effective treatment for the therapy of HPV16-associated lesions. The mechanism underlying the scFv effectiveness appears to be leading cells towards death by apoptosis. Furthermore, the validity of electroporation, a methodology allowed for human treatment, to deliver scFvs to tumors was confirmed.

Immunogenicity of Plant-Produced Human Papillomavirus (HPV) Virus-Like Particles (VLPs).

Cervical cancer is ranked fourth among the top cancers in women and is the second most common cancer in low- and middle-income regions, with ~570,000 new cases reported in 2018, which attributed to 84% of worldwide cervical cancer cases. Three commercially available prophylactic Human papillomavirus (HPV) vaccines are effective at preventing HPV infections. However, these vaccines are expensive due to their complex production systems, therefore limiting their use in developing countries. Recently, the use of plants to produce vaccines has emerged as a cost-effective alternative to conventionally used expression systems. Here, L1 proteins of eight high-risk (HPV 16, 18, 31, 33, 35, 45, 52, and 58) and two low risk (HPV 6 and 34) HPV types were successfully expressed in Nicotiana benthamiana, and transmission electron microscopy (TEM) analysis showed the presence of VLPs and/or capsomeres. Immunogenicity studies were conducted in mice utilizing HPV 35, 52, and 58 and showed that type-specific L1-specific antibodies were produced which were able to successfully neutralize homologous HPV pseudovirions in pseudovirion-based neutralization assays (PBNAs). This work demonstrated the potential for using plant-based transient expression systems to produce affordable and immunogenic HPV vaccines, particularly for developing countries.

Molecular prevalence and phylogenetic analysis of human papillomavirus in normal cervical samples from northern Iran

Cervical infection with the human papillomavirus (HPV) is one of the most common sexually transmitted infections. The aim of this study was to determine the exact types of HPV based on sequencing and cloning of L1 in the north of Iran. In this study, 371 Pap smear samples with normal cytology were collected from health care centers of Mazandaran, Iran. Detection of HPV DNA was performed by PCR amplification of the conserved regions of the L1 gene, then the complete sequence of the L1 gene cloned and sequenced. The HPV genotypes were determined by blast search, then the sequences were compared and the phylogenetic tree was constructed. In this study, the total number of 39 (10.51%) samples out of 371 samples were positive for HPV DNA. The positive samples were identified to be eight HPV types, including 16, 6, 66, 58, 56, 11, 35 and 59. HPV type16 (28.2%) and HPV type 6 (20.51%) were found to be the most prevalent high risk and low risk HPV types in the positive samples, respectively. The prevalence for other types were as fallow: HPV 66 (23.07%), 58 (12.82%), 56 (5.12%), 11(5.12%), 35 (2.56%), 59 (2.56%). Genotyping by DNA sequencing is a reliable, accurate method for HPV screening and genotyping in clinical samples. HPV detection and genotyping in the normal samples is important to evaluate the prevalence of high risk and low risk virus in the population. It is also important for vaccination strategies and the development of type-specific vaccines.

Association of human papilloma virus (HPV) infection with oncological outcomes in urothelial bladder cancer

BackgroundBladder cancer is one of the leading causes of cancer death in adults worldwide. There are various risk factors described for the bladder cancer development including genetic background as well as environmental exposure. Currently, infectious agents such as human papilloma virus (HPV) has also been linked to bladder cancer risk. The current study aimed to evaluate the potential correlation between HPV infection and the oncological outcome in urothelial bladder cancer.MethodsTotally 106 tissue samples of histopathologically confirmed transitional cell carcinoma (TCC) of the urinary bladder were included in this study. The presence of high risk (types 16 and 18) and low risk (types 11 and 6) types of HPV was evaluated using polymerase chain reaction (PCR) followed by in situ hybridization.ResultsOut of 106 bladder cancer patients, a total of 24 cases (22.6%) were positive HPV infection. The most common type of HPV detected was type 16 followed by types 11 and 18, and 6. According to independent T-test results, there was a significant association between mean age and HPV infection (P = 0.015). Moreover, our findings showed a significant relation between infection with HPV and tumor stage, tumor grade, muscle invasion of the tumor, as well as tumor recurrence. The results of Chi-square Test indicated that there is significant statistical association between types of HPV and tumor grade (P-Value = 0.044).ConclusionOur findings indicated that a family history of cancer and HPV infection can be potential independent predictive factors for tumor recurrence in bladder cancer. Overall, the results of this study strongly indicate a significant relationship between HPV infection and an aggravated outcome of the disease and a higher risk of recurrence in patients with bladder cancer.