Human papillomavirus DNA detection in plasma and cervical samples of women with a recent history of low grade or precancerous cervical dysplasia

Cocuzza, Clementina; Martinelli, Marianna; Sina, Federica; Piana, Andrea; Sotgiu, Giovanni; Dell’Anna, Tiziana; Musumeci, Rosario

doi:10.1371/journal.pone.0188592

Cited by 39 publications

(50 citation statements)

References 35 publications

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“…HPV DNA has also been detected in PBMC of patients with cervical cancer . In addition, HPV DNA was detected in serum or plasma of patients with precancerous cervical dysplasia, head and neck squamous cell carcinoma, and oropharyngeal carcinoma . The presence of HPV DNA in blood from these patients has been explained by the presence of metastatic infected cells or remains of HPV‐infected cells in blood.…”

Section: Discussionmentioning

confidence: 99%

Detection and quantitation of human papillomavirus DNA in peripheral blood mononuclear cells from blood donors

Vergara

Balanda

Vidal

et al. 2019

Journal of Medical Virology

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Human papillomavirus (HPV) is the etiological agent of cervical cancer. Also, HPV has been associated with anogenital cancer, oropharyngeal cancer, genital warts, and other dermatological diseases. HPV infects epithelial cells and their replication is closely linked to epithelial differentiation. The presence of HPV DNA in peripheral blood mononuclear cells (PBMC) has been reported in some patients with head and neck cancer, cervical cancer, and other genital diseases. However, the presence of HPV DNA in blood in asymptomatic subjects is still unresolved. The objective of this study was to evaluate the presence of HPV DNA in PBMC from asymptomatic blood donors. Blood samples were collected from 207 healthy Chilean blood donors.Genomic DNA was extracted from PBMC and HPV DNA detection was performed by real-time quantitative polymerase chain reaction assays with GP5+/6+ primers. HPV typing was carried out by genetic sequencing of a 140 to 150 bp fragment of the L1 gene. HPV DNA was detected in 6.8% (14/207) of blood donors. Single HPV infections were detected in seven blood donors. High-risk HPV was found in 6.3% (13/207) of cases: nine blood donors were infected with HPV-16, five with HPV-18, two with HPV-51, and one case was infected with either 32, 33, 45, 59, 66, 70, or 82. The median viral load value was 21.3 copies/mL blood or 13.4 HPV (+) cells per 10 4 PBMC. These results show that HPV DNA is present in PBMC from healthy blood donors and it suggests that blood could be a new route of HPV dissemination. K E Y W O R D S blood donors, HPV DNA detection, human papillomavirus, PBMC

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Section: Discussionmentioning

confidence: 99%

Detection and quantitation of human papillomavirus DNA in peripheral blood mononuclear cells from blood donors

Vergara

Balanda

Vidal

et al. 2019

Journal of Medical Virology

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“…We have shown that PBMCs bind both virus and viral DNA. Other studies have 419 demonstrated that viral DNA can be detected in serum and plasma (Cocuzza et al, 2017;Jeannot 420 et al, 2016). We have detected viral DNA in serum of the infected mice.…”

Section: Viral Dna Was Detected In Blood Samples Of Crpv Infected Rabmentioning

confidence: 96%

Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models

Cladel

Jiang

et al. 2019

Preprint

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Human papillomavirus (HPV) infections are commonly thought to be strictly sexually transmitted. However, studies have demonstrated the presence of HPV in cancers of many non-sexual internal organs, raising the question as to how the viruses gain access to these sites. A possible connection between blood transfusion and HPV-associated disease has not received much attention. We show, in two animal models, that blood infected with papillomavirus yields infections at permissive sites. Furthermore, we demonstrate that blood from actively infected mice can transmit the infection to naïve animals. Finally, we report papillomavirus infections in the stomach tissues of animals infected via the blood. Stomach tissues are not known to be permissive for papillomavirus infection, although the literature suggests that HPVs may be associated with a subset of gastric cancers. These results indicate that the human blood supply, which is not screened for papillomaviruses, could be a potential source of HPV infection and subsequent cancers.SUMMARYHuman papillomaviruses cause 5% of human cancers. Currently, blood banks do not screen for these viruses. We demonstrate that blood transfused from papillomavirus-infected animals produces infections in recipients. Public health implications are significant if the same is true for humans.DefinitionsLocal papillomavirus infection: An infection initiated by the direct application of virus or viral DNA to the site of infectionIntravenous (IV) papillomavirus infection: An infection resulting from blood-borne delivery of virus or viral DNA to the site of infection.

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“…These proof‐of‐concept studies could also be applicable to other viral cancers such as HPV‐induced cervical cancer and hepatitis B/C (HBV/HCV)‐induced liver cancer. HPV‐DNA can be detected in plasma, although the smaller studies published so far show conflicting results regarding whether the presence of cell‐free HPV‐DNA can distinguish between infected individuals, those with precancerous lesions and those with cervical carcinoma . Elevated levels of HBV DNA in serum are a strong predictor of risk of hepatocellular carcinoma , but there are few published studies on the association between plasma hepatitis virus DNA and cancer and its role as a biomarker is therefore not yet established.…”

Section: Can Ctdna Be Used In Cancer Screening Programmes In Defined mentioning

confidence: 99%

Cell‐free tumour DNA testing for early detection of cancer – a potential future tool

et al. 2019

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In recent years, detection of cell‐free tumour DNA (ctDNA) or liquid biopsy has emerged as an attractive noninvasive methodology to detect cancer‐specific genetic aberrations in plasma, and numerous studies have reported on the feasibility of ctDNA in advanced cancer. In particular, ctDNA assays can capture a more ‘global’ portrait of tumour heterogeneity, monitor therapy response, and lead to early detection of resistance mutations. More recently, ctDNA analysis has also been proposed as a promising future tool for detection of early cancer and/or cancer screening. As the average proportion of mutated DNA in plasma is very low (0.4% even in advanced cancer), exceedingly sensitive techniques need to be developed. In addition, as tumours are genetically heterogeneous, any screening test needs to assay multiple genetic targets in order to increase the chances of detection. Further research on the genetic progression from normal to cancer cells and their release of ctDNA is imperative in order to avoid overtreating benign/indolent lesions, causing more harm than good by early diagnosis. More knowledge on the sources and elimination of cell‐free DNA will enable better interpretation in older individuals and those with comorbidities. In addition, as white blood cells are the major source of cell‐free DNA in plasma, it is important to distinguish acquired mutations in leukocytes (benign clonal haematopoiesis) from an upcoming haematological malignancy or other cancer. In conclusion, although many studies report encouraging results, further technical development and larger studies are warranted before applying ctDNA analysis for early cancer detection in the clinic.

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Human papillomavirus DNA detection in plasma and cervical samples of women with a recent history of low grade or precancerous cervical dysplasia

Cited by 39 publications

References 35 publications

Detection and quantitation of human papillomavirus DNA in peripheral blood mononuclear cells from blood donors

Detection and quantitation of human papillomavirus DNA in peripheral blood mononuclear cells from blood donors

Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models

Cell‐free tumour DNA testing for early detection of cancer – a potential future tool

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