Recent Advances on Prediction of Human Papillomaviruses Risk Types

2019 ◽  
Vol 20 (3) ◽  
pp. 236-243
Author(s):  
Yuhua Yao ◽  
Huimin Xu ◽  
Manzhi Li ◽  
Zhaohui Qi ◽  
Bo Liao

Background:Some studies have shown that Human Papillomavirus (HPV) is strongly associated with cervical cancer. As we all know, cervical cancer still remains the fourth most common cancer, affecting women worldwide. Thus, it is both challenging and essential to detect risk types of human papillomaviruses.Methods:In order to discriminate whether HPV type is highly risky or not, many epidemiological and experimental methods have been proposed recently. For HPV risk type prediction, there also have been a few computational studies which are all based on Machine Learning (ML) techniques, but adopt different feature extraction methods. Therefore, we conclude and discuss several classical approaches which have got a better result for the risk type prediction of HPV.Results:This review summarizes the common methods to detect human papillomavirus. The main methods are sequence- derived features, text-based classification, gap-kernel method, ensemble SVM, Word statistical model, position- specific statistical model and mismatch kernel method (SVM). Among these methods, position-specific statistical model get a relatively high accuracy rate (accuracy=97.18%). Word statistical model is also a novel approach, which extracted the information of HPV from the protein “sequence space” with word statistical model to predict high-risk types of HPVs (accuracy=95.59%). These methods could potentially be used to improve prediction of highrisk types of HPVs.Conclusion:From the prediction accuracy, we get that the classification results are more accurate by establishing mathematical models. Thus, adopting mathematical methods to predict risk type of HPV will be the main goal of research in the future.

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Cong Wang ◽  
Yabing Hai ◽  
Xiaoqing Liu ◽  
Nanfang Liu ◽  
Yuhua Yao ◽  
...  

Discrimination of high-risk types of human papillomaviruses plays an important role in the diagnosis and remedy of cervical cancer. Recently, several computational methods have been proposed based on protein sequence-based and structure-based information, but the information of their related proteins has not been used until now. In this paper, we proposed using protein “sequence space” to explore this information and used it to predict high-risk types of HPVs. The proposed method was tested on 68 samples with known HPV types and 4 samples without HPV types and further compared with the available approaches. The results show that the proposed method achieved the best performance among all the evaluated methods with accuracy 95.59% andF1-score 90.91%, which indicates that protein “sequence space” could potentially be used to improve prediction of high-risk types of HPVs.


Author(s):  
Nathalie L. Ambounda ◽  
Sylvain H. Woromogo ◽  
Olive M. Kenmogne ◽  
Felicite E. Yagata Moussa ◽  
Vicky N. Simo Tekem ◽  
...  

Background: High-risk oncogenic human papillomaviruses (HPV) are the cause of sexually transmitted viral infection. Its persistence is a risk factor for precancerous lesions of the cervix, which will constitute the base of cervical cancer. In the world, the prevalence of high-risk oncogenic HPV is 66.7%, which is higher among women starting their sexual activity.Methods: An analytical cross-sectional study was conducted in high schools in Gabon regarding parents. The variables selected were the socio-cultural and demographic characteristics of the parents, their knowledge of human papillomavirus vaccination and their acceptability of HPV vaccination and finally the feasibility of HPV vaccination. The statistical test used was Pearson's Chi-square, and a difference was considered significant for p<0.05.Results: The majority of parents, 89%, were informed of the existence of cervical cancer. However, 73.4% of them were unaware of the existence of vaccination against cervical cancer. Only 2.4% of parents had vaccinated their daughters against cervical cancer at the time of the study. These parents only 53.4% expressed an interest in vaccinating their daughters in 53.4% of cases. The ability to vaccinate children is associated with the socio-professional status of parents (p˂0.000).Conclusions: The majority of parents approved school-based vaccination against human papillomavirus infections despite its reported cost and lack of information. The integration of anti-HPV vaccination into the expanded programme on immunization in Gabon will improve immunization coverage.


2020 ◽  
pp. 1276-1281 ◽  
Author(s):  
Paul Thistle ◽  
Rabea Parpia ◽  
Debanjan Pain ◽  
Hang Lee ◽  
Justen Manasa ◽  
...  

PURPOSE High-risk human papillomaviruses (hrHPV) are the primary cause of cervical cancer. Human papillomavirus (HPV) vaccination is expected to prevent cervical cancers caused by the HPV types included in vaccines and possibly by cross-protection from other types. This study sought to determine the hrHPV type distribution in women at a rural Zimbabwe hospital. METHODS We implemented a cross-sectional study at the Karanda Mission Hospital. Using the Visual Inspection with Acetic Acid Cervicography technique, clinicians collected cervical swabs from 400 women presenting for screening for cervical cancer. Samples were initially analyzed by Cepheid GeneXpert; candidate hrHPV genotypes were further characterized using the Anyplex II HPV28 Detection Kit. RESULTS Twenty-one percent of the 400 women were positive for a high-risk genotype when using the GeneXpert analyzer; 17% were positive when using the multiplex analysis. Almost two thirds of the hrHPV women had a single DNA type identified, whereas one third had multiple genotypes, ranging from 2 to 5. hrHPV was observed more frequently in HIV-positive than in HIV-negative women (27% v 15%). Of the 113 isolates obtained, 77% were hrHPV genotypes not included in the bivalent or quadrivalent vaccines, and 47% represented DNA types not covered in the nonavalent vaccine. Forty-seven percent of the women with hrHPV harbored a single genotype that was not covered by the nonavalent vaccine. CONCLUSION A large fraction of hrHPV isolates from women participating in a cervical cancer screening program in northern Zimbabwe are DNA types not covered by the bivalent, quadrivalent, or nonavalent vaccines. These findings suggest the importance of characterizing the hrHPV DNA types isolated from cervical neoplasia in this population and determining whether cross-immunization against these genotypes develops after administration of the vaccines in current use.


1997 ◽  
Vol 15 (2) ◽  
pp. 610-619 ◽  
Author(s):  
P Viladiu ◽  
F X Bosch ◽  
X Castellsagué ◽  
N Muñoz ◽  
J M Escribà ◽  
...  

PURPOSE To assess whether human papillomavirus (HPV) DNA detection in cervical cancer specimens, or antibodies to selected HPV 16 peptides are predictors of tumor recurrence and long-term survival in patients with squamous cell invasive cervical cancer. SUBJECTS AND METHODS Four hundred seventy-one cases included in two population-based case-control studies underwent follow-up evaluation. The survival and cause of death were ascertained for 410 cases (87%), with a median follow-up time of 4.6 years after diagnosis. HPV DNA was assessed using an L1 polymerase chain reaction (PCR)-based system and Southern hybridization (SH) on scraped cytologic specimens or biopsies. HPV 16 antibodies to E2, L2, and E7 peptides were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS Clinical stage was the only independent prognostic factor for recurrence or survival. Although seropositivity to HPV 16 E7/3 peptide predicted a twofold excess risk of mortality (adjusted hazards ratio [HRa] = 2.0; 95% confidence interval [CI], 1.2 to 3.3), the association was restricted to stage I (HRa = 6.6; 95% CI, 1.2 to 37.6) and II (HRa = 5.9; 95% CI, 2.1 to 16.5) patients. The presence of HPV DNA (HRa = 0.9; 95% CI, 0.5 to 1.5), different estimates of the HPV viral load and the HPV type identified were not predictors of tumor recurrence or survival. CONCLUSION The presence of antibodies to HPV 16 E7 proteins is of prognostic value in early-stage cervical cancer. Our results provide strong evidence that detection and typing of HPV DNA in cervical cells or tissues is not a prognostic factor for recurrence or survival.


Author(s):  
NF Brusnigina ◽  
MA Makhova ◽  
OM Chernevskaya ◽  
KA Orlova ◽  
EA Kolesnikova ◽  
...  

The purpose of the study was to assess detection rates of human papillomavirus in cervical cancer cases of Nizhny Novgorod. Materials and methods. We used the real-time polymerase chain reaction (PCR) to test samples of mucosa lining of the cervical canal and/or transformation zone taken from 630 women with cervical dysplasia of different degrees and 107 incident cases of cervical cancer that did not undergo treatment. The detection and differentiation of 14 genotypes of high-risk human papillomaviruses (HPV) was carried out using the AmpliSens® HPV HCR-genotype-FRT PRC kit. Results. The overall infection rate of women with oncogenic human papillomaviruses was 41.8%. Among the genotypes, HPV 16 (39.2%), 18 (15.5%), 33 (16.6%), and 56 (11.9%) predominated. A high prevalence of oncogenic HPV was detected in the women with cervical intraepithelial neoplasia (58.1%) and cervical cancer (90%). The spectrum of genotypes in women with neoplasia of various degrees differed. In women with CIN II and CIN III, vaccine-preventable HPV genotypes (HPV 16 and 18) playing the leading role in the development of cervical cancer were the most frequent. The same genotypes dominated in the women with invasive cervical cancer. One oncogenic HPV genotype was usually found in the infected women (69%). The high-risk HPV infection was often combined with Ureaplasma ssp (49.3%), Mycoplasma hominis (20.1%), Cytomegalovirus (21.1%), and Herpes simplex I/II (18.2%) infections. Combinations of high-risk HPV with Chlamydia trachomatis and Herpes 6 were found in 8.3% and 5% of the cases, respectively. Conclusions. Our findings proved a wide prevalence of high carcinogenic risk HPV 16 and 18 genotypes, thus indicating the expediency of using Cervarix and Gardasil vaccines registered in the Russian Federation and containing antigens to these types of virus for specific prevention of the HPV infection.


2015 ◽  
Vol 89 (10) ◽  
pp. 5276-5287 ◽  
Author(s):  
Melanie McFarlane ◽  
Alasdair I. MacDonald ◽  
Andrew Stevenson ◽  
Sheila V. Graham

ABSTRACTHigh-risk human papillomaviruses (HR-HPV) cause anogenital cancers, including cervical cancer, and head and neck cancers. Human papillomavirus 16 (HPV16) is the most prevalent HR-HPV. HPV oncogenesis is driven by two viral oncoproteins, E6 and E7, which are expressed through alternative splicing of a polycistronic RNA to yield four major splice isoforms (E6 full length, E6*I, E6*II, E6*X). The production of multiple mRNA isoforms from a single gene is controlled by serine/arginine-rich splicing factors (SRSFs), and HPV16 infection induces overexpression of a subset of these, SRSFs 1, 2, and 3. In this study, we examined whether these proteins could control HPV16 oncoprotein expression. Small interfering RNA (siRNA) depletion experiments revealed that SRSF1 did not affect oncoprotein RNA levels. While SRSF3 knockdown caused some reduction in E6E7 expression, depletion of SRSF2 resulted in a significant loss of E6E7 RNAs, resulting in reduced levels of the E6-regulated p53 proteins and E7 oncoprotein itself. SRSF2 contributed to the tumor phenotype of HPV16-positive cervical cancer cells, as its depletion resulted in decreased cell proliferation, reduced colony formation, and increased apoptosis. SRSF2 did not affect transcription from the P97promoter that controls viral oncoprotein expression. Rather, RNA decay experiments showed that SRSF2 is required to maintain stability of E6E7 mRNAs. These data show that SRSF2 is a key regulator of HPV16 oncoprotein expression and cervical tumor maintenance.IMPORTANCEExpression of the HPV16 oncoproteins E7 and E6 drives HPV-associated tumor formation. Although increased transcription may yield increased levels of E6E7 mRNAs, it is known that the RNAs can have increased stability upon integration into the host genome. SR splicing factors (SRSFs) control splicing but can also control other events in the RNA life cycle, including RNA stability. Previously, we demonstrated increased levels of SRSFs 1, 2, and 3 during cervical tumor progression. Now we show that SRSF2 is required for expression of E6E7 mRNAs in cervical tumor but not nontumor cells and may act by inhibiting their decay. SRSF2 depletion in W12 tumor cells resulted in increased apoptosis, decreased proliferation, and decreased colony formation, suggesting that SRSF2 has oncogenic functions in cervical tumor progression. SRSF function can be targeted by known drugs that inhibit SRSF phosphorylation, suggesting a possible new avenue in abrogating HPV oncoprotein activity.


2020 ◽  
Vol 401 (5) ◽  
pp. 585-599 ◽  
Author(s):  
Om Basukala ◽  
Vanessa Sarabia-Vega ◽  
Lawrence Banks

AbstractHuman papillomaviruses (HPVs) are major human carcinogens, causing around 5% of all human cancers, with cervical cancer being the most important. These tumors are all driven by the two HPV oncoproteins E6 and E7. Whilst their mechanisms of action are becoming increasingly clear through their abilities to target essential cellular tumor suppressor and growth control pathways, the roles that post-translational modifications (PTMs) of E6 and E7 play in the regulation of these activities remain unclear. Here, we discuss the direct consequences of some of the most common PTMs of E6 and E7, and how this impacts upon the multi-functionality of these viral proteins, and thereby contribute to the viral life cycle and to the induction of malignancy. Furthermore, it is becoming increasingly clear that these modifications, may, in some cases, offer novel routes for therapeutic intervention in HPV-induced disease.


2016 ◽  
Vol 150 (3-4) ◽  
pp. 217-226 ◽  
Author(s):  
Ge Gao ◽  
David I. Smith

High-risk human papillomaviruses (HPVs) are known to be associated with different anogenital cancers including cervical, anal, penile, and vaginal cancers. They are also found to be responsible for the dramatic increases in oropharyngeal squamous cell carcinoma (OPSCC) observed in the United States and Europe. The model for how high-risk HPVs induce cancer formation comes from studies of cervical cancer which usually involves integration of the HPV into the human genome and subsequent changes due to induced chromosomal instability. Recent work, discussed here, however suggests that this model may not be completely correct. In addition, we summarize studies now done in OPSCC which demonstrate that the role of HPV in these cancers may be different from that in cervical cancer. Finally, we propose new models for how HPV may be involved in the formation of these 2 cancers.


2013 ◽  
Vol 154 (16) ◽  
pp. 603-618 ◽  
Author(s):  
Péter Bősze

The last 20 years is one of the most remarkable periods in the fight against cancer, with the realization that some human papillomaviruses are causally related to cancer and with the development of the vaccine against human papillomavirus infections. This is a historical event in medicine and the prophylactic human papillomavirus vaccines have provided powerful tools for primary prevention of cervical cancer and other human papillomavirus-associated diseases. This is very important as human papillomavirus infection is probably the most common sexually transmitted infection worldwide, and over one million women develop associated cancer yearly, which is about 5% of all female cancers, and half of them die of their disease. Cancers associated with oncogenic human papillomaviruses, mostly HPV16 and 18, include cervical cancer (100%), anal cancer (95%), vulvar cancer (40%), vaginal cancer (60%), penile cancer (40%), and oro-pharingeal cancers (65%). In addition, pre-cancers such as genital warts and the rare recurrent respiratory papillomatosis are also preventable by vaccination. Currently, the human papillomavirus vaccines have the potential to significantly reduce the burden of human papillomavirus associated conditions, including prevention of up to 70% of cervical cancers. Two prophylactic human papillomavirus vaccines are currently available worldwide: a bivalent vaccine (types 16 and 18), and a quadrivalent vaccine (types 6, 11, 16, and 18). Randomized controlled trials conducted on several continents during the last 10 years have demonstrated that these vaccines are safe without serious side effects; they are highly immunogenic and efficacious in preventing incident and persistent vaccine-type human papillomavirus infections, high grade cervical, vulvar and vaginal intraepithelial neoplasia and so on. In addition, the quadrivalent vaccine has been shown to prevent genital warts in women and men. The vaccine is most effective when given to human papillomavirus naive girls. The human papillomavirus vaccines have been incorporated into national immunization programs in 22 European countries. Routine vaccination is recommended for girls aged between 9 and 13 years and catch-up vaccination for females between 13 and 25 years of age. There is no excuse not to incorporate the vaccines into the Hungarian national immunization program. Albeit vaccination is expensive, it is cost-effective in the long run definitely. Anyway, vaccination is a matter of the specialty and the national health program, but not of business. We all are obliged to prevent human suffering. Orv. Hetil., 2013, 154, 603–618.


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