Methodologies of Primary HPV Testing Currently Applied for Cervical Cancer Screening

Chrysostomou, Andreas; Kostrikis, Leondios G.

doi:10.3390/life10110290

Cited by 27 publications

(49 citation statements)

References 72 publications

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“…These tests have a high inter-observer variability (34-94% sensitivity) as their main limitation [2]. More recently, these tests have been replaced by PCR-based assays for the presence of hrHPV in a number of high-income countries [3]. While having an excellent negative predictive value, these assays lack specificity resulting in unnecessary referrals to a gynecologist and overtreatment (Figure 1).…”

Section: Population Screeningmentioning

confidence: 99%

See 1 more Smart Citation

Molecular markers for cervical cancer screening

Güzel

Hoff

Kok

et al. 2021

Expert Review of Proteomics

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This review gives an overview of current screening practices for cervical cancer. In the introduction, we will cover approaches of population screening focusing on high-risk Human Papilloma Virus (hrHPV) and the need for a better triage assay. We will further assess the impact of current vaccination programs on screening. Subsequently, the review will cover various technological aspects of nucleic acid-and protein-based biomarker assays. We will then detail different molecular markers in view of their use in triage assays, emphasizing epigenetic and protein markers. Finally, we will place this in the context of cost-effectiveness considerations in view of their implementation in high-as well as in low-to middle-income countries. Introduction: Cervical cancer remains a significant healthcare problem, notably in low-to middle-income countries. While a negative test for hrHPV has a predictive value of more than 99.5%, its positive predictive value is less than 10% for CIN2+ stages. This makes the use of a so-called triage test indispensable for population-based screening to avoid referring women, that are ultimately at low risk of developing cervical cancer, to a gynecologist. This review will give an overview of tests that are based on epigenetic marker panels and protein markers. Areas covered: There is a medical need for molecular markers with a better predictive value to discriminate hrHPV-positive women that are at risk of developing cervical cancer from those that are not. Areas covered are epigenetic and protein markers as well as health economic considerations in view of the fact that most cases of cervical cancer arise in low-to-middle-income countries. Expert opinion: While there are biomarker assays based on changes at the nucleic acid (DNA methylation patterns, miRNAs) and at the protein level, they are not widely used in population screening. Combining nucleic acid-based and protein-based tests could improve the overall specificity for discriminating CIN2+ lesions that carry a low risk of progressing to cervical cancer within the screening interval from those that carry an elevated risk. The challenge is to reduce unnecessary referrals without an undesired increase in false-negative diagnoses resulting in cases of cervical cancer that could have been prevented. A further challenge is to develop tests for low-and middle-income countries, which is critical to reduce the worldwide burden of cervical cancer.

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Section: Population Screeningmentioning

confidence: 99%

“…A large number of tests has been developed (ca. 250 tests and more than 450 variants thereof) [29], but only a limited number has been validated [30] and approved for routine screening [3]. These tests may be divided according to the target into (i) viral DNA-and (ii) E6/E7 mRNA-based tests [31].…”

Section: Hrhpv Dna and Mrna Assaysmentioning

confidence: 99%

Molecular markers for cervical cancer screening

Güzel

Hoff

Kok

et al. 2021

Expert Review of Proteomics

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“…There are over 200 types of HPV with 14 strains considered to be associated with cervical cancer [13]. Nearly 80 million people in the United States have been infected with most clearing the infection without incident [14].…”

Section: The Evolution Of Hpv and Typesmentioning

confidence: 99%

“…Patient navigators to increase the vaccination rates and found that white patients are less likely to initiate the HPV vaccine than other ethnicities, however once initiated they were more likely to finish the series [22]. Rural parents were much less likely to encourage HPV vaccines as compared to their urban counterparts [13]. Women in the U.S. in general are basically poorly informed about HPV overall and found therefore, that provider education should target Non-Hispanic Blacks, lower level educated women, and those younger than 65 years of age.…”

Section: Vaccine Hesitancymentioning

confidence: 99%

Preventing Human Papilloma Virus through Community Education and Vaccination

Baldwin¹,

Rinke²

2021

Cervical Cancer - A Global Public Health Treatise

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Human Papilloma Virus (HPV) affects many members of the community. To better educate the community in a participatory manner, engaging those outside of the health care arena is necessary. To prevent the spread of the disease in the United States, reaching the parents of children at the vulnerable age of 9–11 years of age is critical. The barriers to education of parents and children around the spread of a sexually transmitted disease are vast and difficult to overcome. However, the use of proven vaccinations give healthcare providers and community advocates the main tool for prevention of the spread of the disease. It is often taboo to discuss anything related to sexual promiscuity or sexual activity in the United States in the public schools. The biggest myth includes the fear parents and grandparents have is that if HPV is talked about, then the child may become sexually active sooner. This myth needs to be challenged with science and reality including taking on the those vehemently opposed to vaccines, known as “Anti-Vaxers” that obstruct vaccine education. The strategies utilized in public health outreach to the community should be reviewed and uniquely developed for each diverse community to overcome the challenges in the prevention of HPV.

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“…Advances in diagnostic techniques, in particular, the development of easy-to-use molecular genetic tests, are replacing the use of the consolidated Pap test as a screening tool. HPV testing, using HPV DNA from exfoliated cervical cells, has been proposed based on the evidence of the role of "high-risk" types of HPV (especially HPV- 16, 18, 31, 33, 45, 51, 52, and 56) as the etiological agent of cervical cancer [163]. A significant increase in the validity of the available techniques allowed to demonstrate the presence of "highrisk" HPV in a high percentage of both invasive cancers and H-SIL, while the prevalence was low in the healthy population and moderate in L-SIL [164].…”

Section: Specimen Adequacymentioning

confidence: 99%

Genetic Screening of Cervical Cancer

Comparetto¹,

Borruto²

2021

obm genet

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Medical genetics plays an important role in the screening and prevention of numerous diseases. Thus, it is important to develop effective screening and prevention programs and improve the assessment of the susceptibility of diseases. The development of screening and prevention programs depends on the identification of early biomarkers (including functional and behavioral) for the risk and onset of the disease, and such programs need to be designed according to internationally accepted criteria. Cervical cancer represents a very relevant disease from the health and social perspective; around 528,000 new cases are diagnosed every year globally, of which, 85% are from developing countries, representing almost 12% of all cancers in females. Substantial reductions in the incidence of and mortality from cervical cancer have been observed after the introduction of prevention campaigns with the implementation of cervical screening programs through Papanicolaou (Pap) tests and, in particular, following the introduction of organized programs which guarantee a high level of screening coverage, as well as, the quality and continuity of diagnostic-therapeutic procedures. It is estimated that Pap smear screening every 3-5 years provides 80% protection against the onset of cancer. Advances in diagnostic techniques, particularly the development of easy-to-use molecular genetic tests, are replacing the use of the established Pap smear as a screening tool. This is possible owing to the discovery in 1975 that some cellular morphological changes (koilocytosis) were related to the presence of a Human Papillomavirus (HPV) infection. The HPV test is performed on a small sample of cells taken from the cervix, similar to the Pap test; however, it is not a morphological exam but a molecular biology exam that detects the presence of HPV by identifying its deoxyribonucleic acid (DNA) or messenger ribonucleic acid (mRNA). The results of numerous experimental studies have demonstrated a greater sensitivity of this test compared to the sensitivity of the traditional Pap test. However, the HPV test has a lower specificity due to two main factors: 1) The HPV test is based on the search for the types of viruses that have a greater oncogenic potential, and 2) It does not discriminate between transient infections and persistent and productive infections. The most widely used molecular tests are based on the search for HPV sequences and genotyping using molecular biology techniques, such as direct hybridization, qualitative polymerase chain reaction (PCR), and viral nucleotide sequencing.

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Methodologies of Primary HPV Testing Currently Applied for Cervical Cancer Screening

Cited by 27 publications

References 72 publications

Molecular markers for cervical cancer screening

Molecular markers for cervical cancer screening

Preventing Human Papilloma Virus through Community Education and Vaccination

Genetic Screening of Cervical Cancer

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