scholarly journals Circulating HPV DNA in the Management of Oropharyngeal and Cervical Cancers: Current Knowledge and Future Perspectives

2021 ◽  
Vol 10 (7) ◽  
pp. 1525
Author(s):  
Eriseld Krasniqi ◽  
Maddalena Barba ◽  
Aldo Venuti ◽  
Laura Pizzuti ◽  
Federico Cappuzzo ◽  
...  

Human papillomaviruses (HPVs) are associated with invasive malignancies, including almost 100% of cervical cancers (CECs), and 35–70% of oropharyngeal cancers (OPCs). HPV infection leads to clinical implications in related tumors by determining better prognosis and predicting treatment response, especially in OPC. Currently, specific and minimally invasive tests allow for detecting HPV-related cancer at an early phase, informing more appropriately therapeutical decisions, and allowing for timely disease monitoring. A blood-based biomarker detectable in liquid biopsy represents an ideal candidate, and the use of circulating HPV DNA (ct-DNA) itself could offer the highest specificity for such a scope. Circulating HPV DNA is detectable in the greatest part of patients affected by HPV-related cancers, and studies have demonstrated its potential usefulness for CEC and OPC clinical management. Unfortunately, when using conventional polymerase chain reaction (PCR), the detection rate of serum HPV DNA is low. Innovative techniques such as droplet-based digital PCR and next generation sequencing are becoming increasingly available for the purpose of boosting HPV ct-DNA detection rate. We herein review and critically discuss the most recent and representative literature, concerning the role of HPV ctDNA in OPC and CEC in the light of new technologies that could improve the potential of this biomarker in fulfilling many of the unmet needs in the clinical management of OPC and CEC patients.

2019 ◽  
Author(s):  
Noorossadat Seyyedi ◽  
Fatemeh Farjadian ◽  
Ali Farhadi ◽  
Gholamreza Rafiei Dehbidi ◽  
Reza Ranjbaran ◽  
...  

Gold nanoparticles (AuNPs) are commonly used in biosensors of various kinds. The purification of DNA from cancer tissues is an important step in diagnostic and therapeutic development, but current methods are not optimal. Many cervical cancer patients are also susceptible to high-risk human papillomavirus (HR-HPV) infection. Accurate viral diagnosis has so far relied on the extraction of adequate amounts of DNA from formalin-fixed, paraffin-embedded (FFPE) tissue samples. Since the sensitivity and specificity of commercially available purification kits are not optimal, we designed a DNA purification method based on AuNPs to purify sufficient amounts of HR-HPV DNA from cervical cancer tissue samples. AuNPs were coated with a series of oligonucleotide probes to hybridize to specific DNA sequences of HR-HPV genotypes. With this method, we recovered 733 out of 800 copies of type-specific HPV DNA with complete specificity, compared to 36 copies with a standard commercial kit (Qiagen FFPE).


1998 ◽  
Vol 16 (1) ◽  
pp. 330-337 ◽  
Author(s):  
R M Alani ◽  
K Münger

The human papillomaviruses (HPVS) are small DNA tumor viruses that infect epithelial cells and induce proliferative lesions. Substantial epidemiologic data along with in vitro and in vivo studies have led to the implication of particular HPVs with the development of epithelial malignancies. Greater than 90% of all cervical carcinomas are positive for HPV infection. Most of these lesions are caused by infection with mucosal-associated high-risk HPV subtypes. Much work has been undertaken in basic science laboratories to determine the molecular basis for HPV-associated malignancies. Although many significant advances have been made in understanding the biologic properties of these viruses using in vitro analyses, the field has been greatly hindered until recently by the inability to propagate the virus in culture. In this review, we discuss the basic biologic properties of HPVs and the current understanding of the mechanisms of cellular transformation by malignancy-associated viral subtypes. We place particular emphasis on discussion of the HPV oncogenes, E6 and E7. We also discuss premalignant and malignant disorders of squamous and mucosal epithelia, which have been associated with HPV infections, and the current understanding of the mechanism of HPV-associated carcinogenesis in these settings. We focus these discussions on cervical carcinogenesis and briefly review the particulars regarding HPV-associated malignancies in normal and immunocompromised hosts. We end with a discussion of potential targeted molecular therapies for HPV-associated malignancies that may result from the current knowledge of HPV-related cellular growth dysregulation and carcinogenesis.


2007 ◽  
Vol 23 (4) ◽  
pp. 213-227 ◽  
Author(s):  
F. Xavier Bosch ◽  
Silvia de Sanjosé

Cervical cancer has been recognized as a rare outcome of a common Sexually Transmitted Infection (STI). The etiologic association is restricted to a limited number of viral types of the family of the Human Papillomaviruses (HPVs). The association is causal in nature and under optimal testing systems, HPV DNA can be identified in all specimens of invasive cervical cancer. As a consequence, it has been claimed that HPV infection is a necessary cause of cervical cancer. The evidence is consistent worldwide and implies both the Squamous Cell Carcinomas (SCC), the adenocarcinomas and the vast majority (i.e. > 95%) of the immediate precursors, namely High Grade Squamous Intraepithelial Lesions (HSIL)/Cervical Intraepithelial Neoplasia 3 (CIN3)/Carcinomain situ. Co-factors that modify the risk among HPV DNA positive women include the use of oral contraceptives (OC) for five or more years, smoking, high parity (five or more full term pregnancies) and previous exposure to other sexually transmitted diseases such as Chlamydia Trachomatis (CT) and Herpes Simplex Virus type 2 (HSV-2). Women exposed to the Human Immunodeficiency Virus (HIV) are at high risk for HPV infection, HPV DNA persistency and progression of HPV lesions to cervical cancer.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Barbara Golob ◽  
Mario Poljak ◽  
Ivan Verdenik ◽  
Mojca Kolbezen Simoniti ◽  
Eda Vrtačnik Bokal ◽  
...  

Human papillomaviruses (HPV) are the most frequently sexually transmitted viruses and etiological agents of several human cancers. Controversial results of the role of HPV in infertile population on sperm parameters have been published. The aim of this study was to estimate the type-specific prevalence of HPV DNA infection of the external genitalia and semen in 340 Slovenian men from infertile couples and to establish the relationship between seminal HPV DNA infection and abnormal sperm parameters. Self-taken swabs of the entire penile surface and semen samples were collected, and HPV detection and genotyping were performed. HPV DNA was detected in 37.12% of external genitalia and in 13.61% of semen samples with high HPV type concordance of both sampling sites. The most prevalent HPV types in the male external genitalia were HPV-CP6108 and HPV-84. The most prevalent HPV types in semen were HPV-53 and HPV-CP6108. The prevalence of HPV infection between normozoospermic men and men with abnormal sperm parameters did not differ significantly. Sperm quality did not differ significantly between men with seminal HPV infection and uninfected men. In conclusion, the men from infertile couples are equally susceptible to HPV infection regardless of their fertile potential; seminal HPV infection does not impair sperm quality.


1988 ◽  
Vol 99 (3) ◽  
pp. 296-301 ◽  
Author(s):  
Norris K. Lee ◽  
Diane B. Ritter ◽  
Abby E. Gross ◽  
David J. Myssiorek ◽  
Anna S. Kadish ◽  
...  

Human papillomaviruses (HPVs) have been identified in benign and cancerous epithelial lesions of the femal genital tract. They have also been identified in papillomata and cancers of the upper aerodigestive tract. This study investigates the hypothesis that lesions of the cervicovaginal area are more common in women with cancers of the head and neck region. The presence of HPV in lesions of both regions is examined. Seven female patients with cancer of the upper aerodigestive tract had DNA analysis of their carcinoma specimens. HPV type 16 was found in two of the seven (28%). Fourteen female patients with upper aerodigestive tract cancers had Papanicolaou smears to search for cytologic evidence of HPV infection, and cervicovaginal lavages to analyze DNA from exfoliated cervical cells. Five of thirteen (38%) Papanicolaou smears revealed koilocytotic atypia and three of these patients had HPV DNA types 16 or 18 identified in the cervical lavage. The incidence of cervical atypia noted is 13-fold greater than average. One patient had HPV type 16 in both her supraglottic cancer and in her cervicovaginal lavage. Evidence of HPV infection at two separate anatomic sites suggests a systemic susceptibility to HPV infection.


2002 ◽  
Vol 83 (11) ◽  
pp. 2753-2763 ◽  
Author(s):  
Michelle A. Ozbun

Human papillomaviruses (HPVs) are aetiological agents of human malignancies, most notably cervical cancers. The life-cycles of HPVs are dependent on epithelial differentiation, and this has impeded many basic studies of HPV biology. The organotypic (raft) culture system supports epithelial differentiation such that infectious virions are synthesized in raft tissues from epithelial cells that replicate extrachromosomal HPV genomes. The CIN-612 9E cell line maintains episomal copies of HPV type 31b (HPV31b), an HPV type associated with cervical cancers. Many previous studies, including our own, have focused on characterizing the later stages of the HPV31b life-cycle in CIN-612 9E raft tissues. In this study, we have used the raft system to generate large numbers of HPV31b viral DNA (vDNA)-containing particles. We found a biologically contained homogenization system to be efficient at virion extraction from raft epithelial tissues. We also determined that vDNA-containing particles could be directly quantified from density-gradient fractions. Using an RT–PCR assay, the presence of newly synthesized, spliced HPV31b transcripts was detected following HPV31b infection of the immortalized HaCaT epithelial cell line. Spliced E6 and E1∧E4 RNAs were detected using a single round of RT–PCR from cells infected with a dose as low as 1·0 vDNA-containing particle per cell. Spliced E1*I,E2 transcripts were found in cells infected with an HPV31b dose as low as 10 vDNA-containing particles per cell. Infectivity was blocked by HPV31 antiserum, but was not affected by DNase I. This work lays a foundation for a detailed analysis of the early events in HPV infection.


2005 ◽  
Vol 86 (10) ◽  
pp. 2709-2720 ◽  
Author(s):  
Nicolas F. Schlecht ◽  
Robert D. Burk ◽  
Joel M. Palefsky ◽  
Howard Minkoff ◽  
Xiaonan Xue ◽  
...  

Highly oncogenic human papillomavirus (HPV) 16 and 18 variants might be expected to be particularly aggressive in HIV-positive women. The association of HPV16 and 18 variant lineages with race, human immunodeficiency virus (HIV) coinfection, CD4+ T-cell count, HIV-RNA level, time-to-clearance of HPV infection and presence of squamous intraepithelial lesions (SIL) among women in the Women's Interagency HIV Study was studied. Subjects were followed semi-annually with Pap smear and cervicovaginal lavage (CVL). HPV DNA was detected in CVLs using MY09/11 L1 PCR assay. Specimens positive for HPV16/18 underwent E6 PCR and sequencing to determine the variant present. Specimens from 195 HPV16- and 162 HPV18-positive women were classified into variant lineages based on sequencing results. African variants of HPV16 and HPV18 were significantly more prevalent among African-Americans than among Caucasians [42 versus 14 % (P=0·001) and 60 versus 13 % (P<0·001), respectively]. However, it was not possible to detect associations between the HPV16 or 18 variant lineages and other factors studied. African variants of HPV16/18 were more common in women of African descent living outside Africa, which could reflect mixing behaviours and/or immunogenetic factors. However, in a large population of HIV-infected women, the variant of HPV16 or 18 was unrelated to persistence of infection or presence of SIL. If non-European variants are more oncogenic, the effect may involve a late stage in cervical tumorigenesis.


Pathogens ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 267
Author(s):  
Jian Xie ◽  
Pengwei Zhang ◽  
Mac Crite ◽  
Daniel DiMaio

Human papillomaviruses are important pathogens responsible for approximately 5% of cancer as well as other important human diseases, but many aspects of the papillomavirus life cycle are poorly understood. To undergo genome replication, HPV DNA must traffic from the cell surface to the nucleus. Recent findings have revolutionized our understanding of HPV entry, showing that it requires numerous cellular proteins and proceeds via a series of intracellular membrane-bound vesicles that comprise the retrograde transport pathway. This paper reviews the evidence supporting this unique entry mechanism with a focus on the crucial step by which the incoming virus particle is transferred from the endosome into the retrograde pathway. This new understanding provides novel insights into basic cellular biology and suggests novel rational approaches to inhibit HPV infection.


2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Zuyi Chen ◽  
Qiongyao Li ◽  
Qiong Huang ◽  
Huaqing Liu ◽  
Hongwu Jiang ◽  
...  

Abstract Background Human papillomavirus (HPV) is one of the most common sexually transmitted viruses. Data about HPV infection in Guizhou is limited. Methods 56,768 cervical samples were collected and genotyped for 15 main high risk and 6 main low risk HPV types. Results 16.95% (9623/56768) of samples were HPV positive; 90.70% (8728/9623) of HPV positive women were infected by high risk HPV. High risk and high risk mix infection (1458; 70.85%) was the most common mix HPV infection type. The highest HPV detection rate was found in age group 41–45 years old (detection rate = 17.89%) (χ2 = 204.77; P < 0.001); the highest within-group HPV infection rates were found in the ≤20 (25.62%) and ≥ 61 (24.67%) years old age groups, the lowest within-group HPV infection rate was found in the 31–35 years old age group (15.02%). The highest mix infection proportions were found in the ≥61 (36.06%) and ≤ 20 (33.63%) years old age groups (χ2 = 111.21; P < 0.001), the lowest mix infection proportion was found in the 41–45 (17.42%) years old age group. The highest high risk infection proportions were found in the 26–30 (92.98%), ≥61 (92.68%), and 36–40 (92.16%) years old age groups (χ2 = 31.72; P < 0.001), the lowest high risk infection proportion was found in the ≤20 (84.96%) years old age group. HPV infection rates varied with seasons in Guizhou. Conclusions Characteristics of HPV distribution in Guizhou were identified. There were significant differences in HPV distribution among age groups, prevention strategies should be adjusted according to the characteristics.


2020 ◽  
Author(s):  
Nara Diniz Soares Pessoa ◽  
Thatiana Correia Melo ◽  
Rodrigo Pinheiro Araldi ◽  
Rofrigo Franco Carvalho ◽  
Willy Becak ◽  
...  

In this study, we evaluated the presence of early and late Human Papillomavirus (HPV) proteins in retinoblastoma Brazilian patients. For this, 8 formalin-fixed paraffin-embedded retinoblastoma tissue blocks were used. HPV DNA presence was determined by in situ hybridization (ISH). Immunohistochemistry were performed to verify HPV16/18 E6, E1^E4, and L1 proteins. HPV was detected in all retinoblastoma tumors and viral DNA was labeled in tumor cells, retinal layers and optical nerve structures. In addition, E1^E4, E6 and L1 proteins were detected in all samples in the same areas where HPV DNA was detected. Our data showed the presence and expression of early and late HPV proteins in retinoblastoma tumors from Brazilian children. However, further studies should be performed to clarify the role of HPV infection in retinoblastoma tumor.


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