scholarly journals Patogenesis Human Papillomavirus (HPV) pada Kanker Serviks

2019 ◽  
Vol 8 (1) ◽  
pp. 23-32
Author(s):  
Paulina Rosa Evriarti ◽  
Andi Yasmon

AbstractCervical cancer is the most common cancer among women in the world. The main cause of the development of cervical cancer is due to persistent infection of a high-risk type (HR) - Human Papillomavirus (HPV). The mechanisms of HPV in causing cervical cancer are discussed in this article that collected from current information published in a scientific journal. The main target of HPV infection is the basal layer of cervical epithelia and the virus could reach its target when there is a microabrasion of epithelial cells. The HPV binds to its specific receptor on the host cellular surface and followed by the entering virus into the cytoplasm through the endocytosis process. After successfully entering the cell, the virus will uncoat and begin the replication process by hijacking the transcription and translation system of host cells. E6 and E7 proteins play an important role in the inactivation of tumor suppressor proteins p53 and pRb, causing the cells to uncontrolled divide (immortal). If the immune response failed to interfere with the replication process and eliminates HPV-infected cells, the HPV infection will lead to cervical cancer. In conclusion, the mechanism of HPV causing cervical cancer is complex and involves important proteins of HPV. AbstrakKanker serviks merupakan kanker paling banyak kedua yang diderita oleh perempuan di dunia. Penyebab utama dari perkembangan kanker serviks yakni adanya infeksi yang persisten tipe high risk (HR) – Human Papillomavirus (HPV). Artikel ini disusun untuk mengetahui mekanisme HPV dalam menimbulkan kanker serviks. Uraian dan tulisan mengenai isi artikel ini diperoleh dengan melakukan beberapa studi literatur yang terkait dengan HPV dalam menyebabkan kanker serviks. HPV dalam perannya menimbulkan kanker serviks diawali dengan masuknya HPV ke dalam lapisan sel epitel pejamu karena adanya mikroabrasi atau luka kecil. Bila berhasil melakukan pelekatan pada sel epitel serviks melalui reseptornya, virus akan diendositosis dan masuk ke dalam sel. Setelah berhasil masuk sel, virus akan mengalami uncoating, kemudian virus akan memulai proses replikasinya dengan cara mengambil alih sistem transkripsi dan translasi sel pejamu. Protein E6 dan E7 berperan penting dalam hal ini karena adanya kedua protein tersebut menghalangi kerja dari protein supressor tumor p53 dan pRb sehingga sel menjadi imortal dan pembelahan sel menjadi tidak terkendali. Apabila proses ini terakumulasi tanpa berhasil dieliminasi oleh sistem imun, infeksi oleh virus HPV dapat menjadi persisten dan timbul suatu keganasan berupa kanker serviks. Dari paparan tersebut, dapat ditarik kesimpulan bahwa mekanisme HPV dalam menyebabkan kanker serviks merupakan mekanisme yang cukup kompleks dan melibatkan protein-protein penting yang ada dalam genom HPV.

2019 ◽  
Author(s):  
Li Song ◽  
Yuanjing Lyu ◽  
Ling Ding ◽  
Xiaoxue Li ◽  
Wen Gao ◽  
...  

Abstract Background: High-risk human papillomavirus (HR-HPV) infection is widely known as the major cause of cervical intraepithelial neoplasia (CIN) and cervical cancer and it’s characteristics vary greatly in different population. Women with abnormal cervical cytology could increase the risk of cervical cancer, however, HR-HPV infection characteristics in women with abnormal cervical cytology remains unclear. Methods: This study was based on baseline survey of the CIN Cohort established in Shanxi Province, China. A total number of 2300 women with cervical abnormalities were enrolled in this study. All participants gave informed consent and agreed to HPV and thinprepcytologic test (TCT). Each individual completed a questionnaire about characteristics related to HPV infection. Results: The overall prevalence of HR-HPV in 2300 women was 32.0%, and the proportion of single and multiple HR-HPV infections were 70.2% and 29.8% in HR-HPV infection women, respectively. The top five HR-HPV genotypes were ranked as HPV16, HPV58, HPV52, HPV53 and HPV51. The prevalence of HR-HPV in atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion and above(HSIL+) were 30.8%, 36.5% and 54.9%, respectively, showing an increasing trend with the severity of cervical cytology ( χ 2 trend =13.952; p <0.001). The women aged 35~45 years, with lower education level, less frequency of bathing, multiple gravidity, multiple parity, history of gynecological diseases and premenopausal women were prone to HR-HPV infection. Conclusions: We defined the characteristics related to HR-HPV infection in abnormal cervical cytology women, and provided an insight for the development and deeply research of HPV vaccine.


2015 ◽  
Vol 9 (06) ◽  
pp. 571-576 ◽  
Author(s):  
Fatimah Saeed Alhamlan ◽  
Ahmed A Al-Qahtani ◽  
Mohammed N Al-Ahdal

Human papillomavirus (HPV) infection is a significant etiological factor and an important prognosticator in cervical cancer. Indeed, researchers worldwide have confirmed these roles for high-risk HVPs in over 70% of cervical cancer cases. According to the World Health Organization, approximately 561,200 new cancer cases (5.2% of all new cancers) are attributed to HPV infection. Over 120 types of HPV are classified further as either low-risk HPV (LR-HPV) or high-risk HPV (HR-HPV) based on their oncological potential of transforming cells. The LR-HPV types cause benign hyperproliferative lesions (i.e. genital warts) while the HR-HPV types are strongly associated with premalignant and malignant cervical lesions. Data on the prevalence of HPV, survival of infected patients, and mortality rate are scarce in Saudi Arabia. The unsubstantiated assumption of a low prevalence of HPV in Saudi Arabia has contributed to limiting HPV research in this conservative country. Therefore, the goal of this review is to shed light on the current HPV research being conducted and the prevalence of HPV in Saudi Arabia.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yan Shen ◽  
Jing Xia ◽  
Huihui Li ◽  
Yang Xu ◽  
Sanping Xu

Abstract Background The incidence rate of cervical cancer is increasing yearly. The persistent infection of high-risk human papillomavirus (HPV) is the main factor leading to cervical cancer. HPV infection is double peak type. This study aimed at analyzing the HPV distribution characteristics, infection rate, and risk of age in pre- and postmenopausal women. So as to provide reference for the prevention of HPV infection and cervical cancer screening strategy. Methods A retrospective analysis of 4614 women who underwent cervical cytology, and HPV examination from January 2018 to October 2019 at the healthcare department of Wuhan Union Hospital was done. We explored the characteristics and distribution of HPV infections around the menopause, then comparing the infection rate of HPV in postmenopause and over 65 years old, in order to analyze the influence of different ages on HPV infection. Results Generally, the HPV infection rate was 13.10% (539/4115), whereby the high-risk subtype constituted 73.84% (398/539) of all positive cases. On the other hand, the HPV39 infection was more common in postmenopausal women; however, there was no significant difference in the distribution of the other types in the pre- and postmenopausal women. The first four types were 52/53/58/16. The results further showed that the rates of HPV infection before and after menopause were 12.34% (367/2975) and 15.09% (172/1140), respectively, which had no significant difference (P = 0.056), but more susceptible to high-risk HPV infection after the age of 65 (P = 0.041). Except for 40 years old to menopause, the infection rate of high-risk HPV in this age group was different from that in postmenopause (P = 0.023, 0.729 (0.555, 0.957)), other age groups had no significant effect on high-risk HPV infection. Conclusions It was concluded that whether menopause has nothing to do with HPV infection. Moreover, the risk of high-risk HPV infection in women aged 40 to premenopausal is relatively low, but the infection rate increases after 65. Hence the cutoff screening age should be appropriately prolonged.


2021 ◽  
Vol 118 (41) ◽  
pp. e2108359118
Author(s):  
Alejandra García ◽  
Giovanna Maldonado ◽  
José L. González ◽  
Yuri Svitkin ◽  
David Cantú ◽  
...  

Cervical cancer is the fourth most common cause of cancer in women worldwide in terms of both incidence and mortality. Persistent infection with high-risk types of human papillomavirus (HPV), namely 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68, constitute a necessary cause for the development of cervical cancer. Viral oncoproteins E6 and E7 play central roles in the carcinogenic process by virtue of their interactions with cell master proteins such as p53, retinoblastoma (Rb), mammalian target of rapamycin (mTOR), and c-MYC. For the synthesis of E6 and E7, HPVs use a bicistronic messenger RNA (mRNA) that has been studied in cultured cells. Here, we report that in cervical tumors, HPV-18, -39, and -45 transcribe E6/E7 mRNAs with extremely short 5′ untranslated regions (UTRs) or even lacking a 5′ UTR (i.e., zero to three nucleotides long) to express E6. We show that the translation of HPV-18 E6 cistron is regulated by the motif ACCaugGCGCG(C/A)UUU surrounding the AUG start codon, which we term Translation Initiation of Leaderless mRNAs (TILM). This motif is conserved in all HPV types of the phylogenetically coherent group forming genus alpha, species 7, which infect mucosal epithelia. We further show that the translation of HPV-18 E6 largely relies on the cap structure and eIF4E and eIF4AI, two key translation initiation factors linking translation and cancer but does not involve scanning. Our results support the notion that E6 forms the center of the positive oncogenic feedback loop node involving eIF4E, the mTOR cascade, and p53.


2011 ◽  
Vol 6 (1) ◽  
pp. 31-44
Author(s):  
Indra Balachandran

High-risk human papillomavirus (HPV) infection and viral persistence is a major risk factor in the development of squamous intraepithelial lesions and invasive carcinoma of the cervix. In the United States, deaths due to squamous cell carcinoma of the cervix have fallen by 75% since the 1960s because of Papanicolaou (Pap) smear screening. However, the traditional Pap had a sensitivity of about 70% for detecting clinically significant precancerous lesions and cancer because of sampling and interpretive errors. The introduction of 2 liquid-based Pap smear collection systems in the 1990s, the use of HPV testing as a triage and co-testing with Pap smear, and the introduction of 2 automated screening devices have had a significant impact on improving the detection of such precancerous lesions. This review provides an analysis of the changes in Pap smear collection, improvements in screening, the evolutionary changes of high-risk HPV testing, reporting terminology of Pap smears, and clinical management guidelines. The future impact of 2 prophylactic HPV vaccines on the incidence of cervical carcinoma is also discussed. This article also discusses alternatives such as primary screening for high-risk HPV testing with visual inspection for cervical cancer detection used in resource-poor settings with a high incidence of cervical cancer.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1008
Author(s):  
Andrejs Lifsics ◽  
Valerija Groma ◽  
Maksims Cistjakovs ◽  
Sandra Skuja ◽  
Renars Deksnis ◽  
...  

Human papillomavirus (HPV) was proven to play a significant role in cancer development in the oropharynx. However, its role in the development of laryngeal (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) remains to be clarified. High-risk HPV (HR-HPV) viral proteins E6 and E7 are considered to be pertinent to HPV-related carcinogenesis. Hence, our aim was to estimate LSCC and HPSCC for HR-HPV DNA, p16, and E6/E7 oncoprotein status by using molecular virology and immunohistochemistry methods. The prevalence of HPV16 infection was 22/41 (53.7%) and 20/31 (64.5%) for LSCC and HPSCC, accordingly. The majority of HPV16+ tumor samples were stage III or IV. In most samples, the presence of either HPV16 E6 or HPV16 E7 viral protein in dysplastic or tumor cells was confirmed using immunohistochemistry. Our results suggest a high prevalence of HPV16 as a primary HR-HPV type in LSCC and HPSCC. The lack of HPV E6/E7 oncoproteins in some tumor samples may suggest either the absence of viral integration or the presence of other mechanisms of tumorigenesis. The utilization of p16 IHC as a surrogate marker of HR-HPV infection is impractical in LSCC and HPSCC.


2021 ◽  
Author(s):  
Sunardhi Widyaputra ◽  
Natallia Pranata ◽  
Ignatius Setiawan ◽  
Jamas Ari Anggraini

Human papillomavirus (HPV) infection accounts for approximately 5.2% of the worldwide human cancer burden. Molecular epidemiologic evidence clearly indicates that certain types of HPV are the principal cause of both cervical and oral cancers. Major oncoproteins E6 and E7 can inactivate p53 and pRB proteins because it happened genome instability and dysregulation host cell cycles. This virus is an epithelial tropism, vulnerable area mainly at the basal layer and epithelial stem cell, because it still has a high proliferation capacity, so it can support the replication of the virus. Virions bind initially to the glycosaminoglycan (GAG) chains of heparan sulphate proteoglycan (HSPG). More than 99% cervical cancer arise at the cervical transformation zone. In oral cavity, exposed areas of the basal layer will be very susceptible to HPV infection. The HPV presence in the oral area is considered as one of the etiologics of oral cancer in those who do not have bad habits such as smoking, betel chewing, or poor oral hygiene. Our study successfully identified HPV type 58 in dental calculus. Dental calculus, calcified oral plaque biofilm, has been shown to be an abundant, nearly ubiquitous, and long-term reservoir of the ancient oral microbiome, including bacteria, archaea, eukaryote, and viruses. During biomineral maturation process, several biological contents around the oral region should be trapped, including the exfoliated virus contained cells. Dental calculus is a promising source of HPV and carcinogens molecules in the oral cavity and could be used as a biomarker for early detection.


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.


2020 ◽  
Author(s):  
Jacqueline Monteiro ◽  
Ricardo Roberto de Souza Fonseca ◽  
Tuane Ferreira ◽  
Luana Rodrigues ◽  
Andreza Silva ◽  
...  

Abstract Background: Human papillomavirus (HPV) is the most common sexually transmitted disease in the world. Several studies have shown a higher prevalence of HPV infection in HIV-infected women. The aim of this study was to determine the prevalence and the genotype diversity of HPV infection in HIV-infected women.Methods: From April 2010 to December 2012 cervical specimens were collected from 169 HIV-infected women who screening for cervical cancer at Reference Unit in Belém. The detection of HPV infection was performed by nested PCR and HPV type was performed using the commercial kit.Results: The prevalence of HPV infection was 63,3%. Of the 47 genotyped samples, 40,4% was found positive for high risk-HPV 16 and 12.8% for high risk-HPV 52. HPV infection was predominant in the group of women with no incidence of cytological abnormalities and more prevalent in women of reproductive age, unmarried, low education level and who used condoms during sexual intercourse. It was observed an association between HPV infection and independent variables, such as condom use, multiple sexual partners and history of sexually transmitted diseases.Conclusions: High-risk types of HPV infection were prevalent in our study. Infection with multiple high-risk HPV genotypes may potentiate the development of cervical cancer in HIV-infected women.


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