HPV-mediated Cervical Cancer: A Systematic review on Immunological Basis, Molecular Biology and Immune evasion mechanisms

2021 ◽  
Vol 23 ◽  
Author(s):  
Ramar Vanajothi ◽  
Natarajan Srikanth ◽  
Rajendran Vijayakumar ◽  
Manikandan Palanisamy ◽  
Sundaresan Bhavaniramya ◽  
...  

Background: Human papillomavirus (HPV), one of the most frequently transmitted viruses globally, causing several malignancies including cervical cancer Aim: Owing to their unique pathogenicity HPV viruses can persist in the host organism for a longer duration than other virus types, to complete their lifecycle. During its association with the host, HPV causes various pathological conditions affecting the immune system by evading the host immune- mechanisms leading to the progression of various diseases, including cance Method: To date, ~ 150 serotypes were identified, and certain high-risk HPV types are known to be associated with genital warts and cervical cancer. As of now, two prophylactic vaccines are in use for the treatment of HPV infection, however, no effective antiviral drug is available for HPV-associated disease/infections. Numerous clinical and laboratory studies are being investigated to formulate an effective and specific vaccine again HPV infections and associated diseases Result: As the immunological basis of HPV infection and associated disease progress persist indistinctly, deeper insights on immune evasion mechanism and molecular biology of disease would aid in developing an effective vaccine. Conclusion: Thus this review focuses, aiming a systematic review on the immunological aspects of HPV-associated cervical cancer by uncovering immune evasion strategies adapted by HPV.

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 714
Author(s):  
Matthias Läsche ◽  
Horst Urban ◽  
Julia Gallwas ◽  
Carsten Gründker

Cervical cancer is responsible for around 5% of all human cancers worldwide. It develops almost exclusively from an unsolved, persistent infection of the squamocolumnar transformation zone between the endo- and ecto-cervix with various high-risk (HR) human papillomaviruses (HPVs). The decisive turning point on the way to persistent HPV infection and malignant transformation is an immune system weakened by pathobionts and oxidative stress and an injury to the cervical mucosa, often caused by sexual activities. Through these injury and healing processes, HPV viruses, hijacking activated keratinocytes, move into the basal layers of the cervical epithelium and then continue their development towards the distal prickle cell layer (Stratum spinosum). The microbial microenvironment of the cervical tissue determines the tissue homeostasis and the integrity of the protective mucous layer through the maintenance of a healthy immune and metabolic signalling. Pathological microorganisms and the resulting dysbiosis disturb this signalling. Thus, pathological inflammatory reactions occur, which manifest the HPV infection. About 90% of all women contract an HPV infection in the course of their lives. In about 10% of cases, the virus persists and cervical intra-epithelial neoplasia (CIN) develops. Approximately 1% of women with a high-risk HPV infection incur a cervical carcinoma after 10 to 20 years. In this non-systematic review article, we summarise how the sexually and microbial mediated pathogenesis of the cervix proceeds through aberrant immune and metabolism signalling via CIN to cervical carcinoma. We show how both the virus and the cancer benefit from the same changes in the immune and metabolic environment.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1576-1576
Author(s):  
Sally Nneoma Akarolo-Anthony ◽  
Celestine C. Ogbonna ◽  
Oluranti Ayotunde Famooto ◽  
Eileen O. Dareng ◽  
Maryam Al-Mujtaba ◽  
...  

1576 Background: The incidence of cervical cancer has remained stable in HIV+ women but the prevalence and multiplicity of high risk HPV (hrHPV) infection, a necessary cause of cervical cancer, appears different comparing HIV+ to HIV- women. Because this has not been well studied in Africa, we conducted this study to identify single and multiple hrHPV infection among HIV+ and HIV- women in Nigeria. Methods: We enrolled HIV+ and HIV- women presenting at our cervical cancer screening program in Abuja, Nigeria between April 2012 and August 2012. Using a nurse administered questionnaire, we collected information on demographic characteristics, risk factors of HPV infection and cervical exfoliated cells samples from all participants. We used Roche Linear Array HPV Genotyping Test to characterize the prevalent HPV according to manufacturer’s instruction and logistic regression models to estimate the association between HIV infection and the risk of high-risk HPV infection. Results: There were 278 participants, 40% (111) of whom were HIV negative, 54% (151) HIV positive and 6% (16) with HIV status unknown. Of these, 108 HIV+ women cases and 149 HIV- women controls were available for analysis. The mean ages (±SD) were 37.6 (±7.7) for HIV+ and 36.6 (±7.9) years for HIV- women (p-value = 0.34). Cases and controls had similar socio-demographic characteristics. Among HIV+ women, HPV35 (8.7%) and HPV56 (7.4%) were the most prevalent hrHPV, while HPV52 and HPV68 (2.8%, each) were the most prevalent among HIV- women. The age adjusted RR for prevalent hrHPV was 4.18 (95% CI 2.05 – 8.49, p-value <0.0001), comparing HIV+ to HIV- women. The multivariate RR for any HPV and multiple hrHPV was 3.75 (95% CI 2.08 – 6.73, p-value 0.01) and 6.6 (95% CI 1.49 – 29.64, p-value 0.01) respectively, comparing HIV+ to HIV- women, adjusted for age, and educational level. Conclusions: HIV infection was associated with increased risk of any HPV, hrHPV and multiple HPV infections. Oncogenic HPV types 35, 52, 56 and 68 may be more important risk factors for cervical pre-cancer and cancer among women in Africa. Polyvalent hrHPV vaccines meant for African populations should protect against HPV types other than 16 and 18.


2016 ◽  
Vol 5 (4) ◽  
pp. 99-104
Author(s):  
Jin Zhang

AbstractHuman papillomavirus (HPV) is a DNA virus that infects the skin and mucous membranes of the human body. Approximately 80% of sexually active women are likely infected with HPV. Cervical cancer is one of the most common malignant tumors and is second in incidence only to breast cancer. Infection with high-risk HPV types is the main risk factor for cervical cancer, which is currently the only malignant tumor with a clearly defined etiology. HPV infection is also closely related to the incidence and development of other malignant tumors. In addition to cervical cancer, HPV can cause other urogenital tumors, as well as tumors in the digestive tract, lungs, eyes, skin, and other organ systems. This paper provides a review of the progress in HPV infection-related research and provides novel ideas for the study of tumor etiology and mechanisms.


2005 ◽  
Vol 16 (2) ◽  
pp. 83-91 ◽  
Author(s):  
François Coutlee ◽  
Danielle Rouleau ◽  
Alex Ferenczy ◽  
Eduardo Franco

Human papillomaviruses (HPVs) are the etiological agents of several genital cancers, including cancer of the uterine cervix. The detection of HPV infection in genital samples may increase the sensitivity of primary and secondary screenings of cervical cancer. HPV testing may also improve the specificity of screening programs, resulting in the avoidance of overtreatment and cost savings for confirmatory procedures. The major determinants of clinical progression of HPV infection include persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load, integration of viral DNA and presence of several potential cofactors. Signal amplification HPV-DNA detection techniques (Hybrid Capture II, Digene Corporation, USA) are standardized, commercially available, and capable of detecting several high-risk HPV types. They also increase the sensitivity of screening for high-grade lesions in combination with cytology. The sensitivity of these techniques to detect high-grade lesions is higher than that of cytology, but the referral rate for colposcopy is greater. These techniques are approved for the triage to colposcopy of women with cervical smears interpreted as atypical squamous cells of undetermined significance. Triage and screening for cervical cancer using HPV will probably be restricted to women aged 30 years or older because of the high prevalence of infection in younger women. Amplification techniques are ideal for epidemiological studies because they minimize the misclassification of HPV infection status. These techniques can detect low HPV burden infections. Consensus primers amplify most genital types in one reaction, and the reverse hybridization of amplicons with type-specific probes allows for the typing of HPV-positive samples. Consensus PCR assays are currently under evaluation for diagnostic purposes. HPV testing is currently implemented for the clinical management of women.


2020 ◽  
Author(s):  
Jude Ogechukwu Okoye ◽  
Simon Imakwu Okekpa ◽  
Chiemeka Franklin Chukwukelu ◽  
Ifeoma Nora Onyekachi-Umeh ◽  
Anthony Ajuluchukwu Ngokere

SummaryBackgroundCervical Cancer is the 6th most common and 3rd most deadly cancer among women. Despite the fact that majority of the countries in Asia and Africa have similar economy and low life expectancy, the mean age standardized incidence rate (ASIR) of cervical cancer is substantially higher in Africa than Asia. Thus, this study aimed to identify the correlates of the higher ASIR rates in Africa relative to Asia.MethodsPeer-reviewed articles published between 2004 and 2017 were selected using the PRISMA standard. Sources of articles include Google Scholar, Scopus, PubMed Central, and EMBASE. Search keywords included: HPV genotypes, cervical cancer, HPV vaccine, and multiple infection in Africa and Asia.ResultA total of 29 and 17 full-length articles were selected from Africa and Asia respectively. Based on estimates in the general population, the incidence of high-risk HPV (hrHPV) types in Africa and Asia was 3.5 and 1.0 respectively. The prevalence of HPV infection was higher in Africa than in Asia (p< 0.001). The prevalence of HPV infection between 2004-2009 and 2010-2017 decreased in Africa but increased in Asia. More so, the prevalence of multiple HPV and non-vaccine HPV infection were higher in Africa than Asia (p< 0.001). The prevalent HPV types in Africa were HPV16, HPV18, and HPV52, while that of Asia were HPV16, HPV52, and HPV58, in descending order of prevalence. This study revealed that nonavalent HPV vaccine could prevent the development of 69.3% and 83.2% of HPV associated cervical abnormalities in Africa and Asia, respectively.ConclusionThis study revealed higher prevalence of HPV infection and multiple HPV infection in Africa compared with Asia, which could be responsible for the higher ASIR in Africa. It suggests that nonavalent vaccination including cervical screening using Pap smear could prevent over 90% of the cervical abnormalities in Africa.


2018 ◽  
Vol 19 (11) ◽  
pp. 3297 ◽  
Author(s):  
Wieke Kremer ◽  
Marjolein van Zummeren ◽  
Daniëlle Heideman ◽  
Birgit Lissenberg-Witte ◽  
Peter Snijders ◽  
...  

Data on human papillomavirus (HPV) type-specific cervical cancer risk in women living with human immunodeficiency virus (WLHIV) are needed to understand HPV–HIV interaction and to inform prevention programs for this population. We assessed high-risk HPV type-specific prevalence in cervical samples from 463 WLHIV from South Africa with different underlying, histologically confirmed stages of cervical disease. Secondly, we investigated DNA hypermethylation of host cell genes ASCL1, LHX8, and ST6GALNAC5, as markers of advanced cervical disease, in relation to type-specific HPV infection. Overall, HPV prevalence was 56% and positivity increased with severity of cervical disease: from 28.0% in cervical intraepithelial neoplasia (CIN) grade 1 or less (≤CIN1) to 100% in invasive cervical cancer (ICC). HPV16 was the most prevalent type, accounting for 9.9% of HPV-positive ≤CIN1, 14.3% of CIN2, 31.7% of CIN3, and 45.5% of ICC. HPV16 was significantly more associated with ICC and CIN3 than with ≤CIN1 (adjusted for age, ORMH 7.36 (95% CI 2.33–23.21) and 4.37 (95% CI 1.81–10.58), respectively), as opposed to non-16 high-risk HPV types. Methylation levels of ASCL1, LHX8, and ST6GALNAC5 in cervical scrapes of women with CIN3 or worse (CIN3+) associated with HPV16 were significantly higher compared with methylation levels in cervical scrapes of women with CIN3+ associated with non-16 high-risk HPV types (p-values 0.017, 0.019, and 0.026, respectively). When CIN3 and ICC were analysed separately, the same trend was observed, but the differences were not significant. Our results confirm the key role that HPV16 plays in uterine cervix carcinogenesis, and suggest that the evaluation of host cell gene methylation levels may monitor the progression of cervical neoplasms also in WLHIV.


2018 ◽  
Vol 7 (1) ◽  
pp. 12-17 ◽  
Author(s):  
Ting Miao

Abstract Persistent infection by human papillomavirus (HPV) is an important factor causing cervical cancer. In recent years, infection with multiple HPV types has been confirmed in various studies. High-risk HPV 16 and 18 and low-risk HPV 6 are the most common causes of multitype HPV infection. Infection with multiple types of HPV, which results from individual susceptibility, is crucial in tumor susceptibility. This paper summarizes the common types of multiple HPV infection to enable further research on the relationship between HPV and tumor susceptibility.


Medicina ◽  
2021 ◽  
Vol 57 (10) ◽  
pp. 1025
Author(s):  
Agne Vitkauskaite ◽  
Joana Celiesiute ◽  
Vijoleta Juseviciute ◽  
Kristina Jariene ◽  
Erika Skrodeniene ◽  
...  

Our study aimed to evaluate the distribution of genotypes and allele frequencies of IL-6 597A/G (rs1800797) and 174G/C (rs1800795) polymorphisms in HPV infected and uninfected healthy women and cervical cancer patients. A PCR based Multiplex HPV genotyping test kit was used for in vitro detection and differentiation of high risk HPV genotypes. Genotyping of two polymorphisms, IL-6 597A/G (rs1800797) and 174G/C (rs1800795), was performed using the KASP genotyping assay kit. Cervical cancer patients were more likely to be HPV positive than control patients. Allele C of IL-6 rs1800795 was associated with a higher risk of cervical cancer by 2.26-fold and genotype CC by 5.37-fold. Genotype CC of IL-6 rs1800795 was more frequent in the HPV positive group compared with the HPV negative group (p = 0.002). Allele G of IL-6 rs1800797 was more frequently found in women with HPV16/HPV18 compared to other HPV types (p = 0.045). Women with AA genotypes of IL-6 rs1800797 were less frequently infected with HPV16/HPV18 compared to other HPV types (p = 0.045). The major finding of the study is the significant association of C allele and CC genotype of IL-6 1800795 gene with cervical cancer in the Lithuanian population. Genotype CC of IL-6 rs1800795 has a significant association with HPV infection as well.


2017 ◽  
pp. 99-103
Author(s):  
Van Bao Thang Phan ◽  
Hoang Bach Nguyen ◽  
Van Thanh Nguyen ◽  
Thi Nhu Hoa Tran ◽  
Viet Quynh Tram Ngo

Introduction: Infection with HPV is the main cause of cervical cancer. Determining HPV infection and the types of HPV plays an important role in diagnosis, treatment and prognosis of cervicitis/cervical cancer. Aims: Determining proportion of high-risk HPV types and the occurrence of coinfection with multiple HPV types. Methods: 177 women with cervicitis or abnormal Pap smear result were enrolled in the study. Performing the real-time PCR for detecting HPV and the reverse DOT-BLOT assay for determining type of HPV in cases of positive PCR. Results: 7 types of high-risk HPV was dectected, the majority of these types were HPV type 18 (74.6%) and HPV type 16 (37.6%); the proportion of infection with only one type of HPV was 30.4% and coinfection with multiple HPV types was higher (69.6%), the coinfected cases with 2 and 3 types were dominated (32.2% and 20.3%, respectively) and the coinfected cases with 4 and 5 types were rare. Conclusion: Use of the real-time PCR and reverse DOT-BLOT assay can determine the high-risk HPV types and the occurrence of coinfection with multiple HPV types. Key words: HPV type, Reverse DOT-BLOT, real-time PCR,PCR, cervical cancer


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