Chapter Four - Human Papillomavirus and Its Testing Assays, Cervical Cancer Screening, and Vaccination
Introduction
Human papillomaviruses (HPVs) are a group of about 200 related viruses. More than 40 HPV types can cause sexually transmitted diseases through direct sexual contact such as vaginal, anal, and oral sex. Low-risk HPVs transmitted by sex may result in condylomata acuminata (skin warts) on or around the genitals, anus, mouth, or throat, while high-risk HPVs (hrHPVs) are responsible for HPV-induced cervical, anogenital, oropharyngeal, and other rarer cancers. The HPV genome is incorporated into the host genome, and in particular, the incorporation of E6/E7 genes and subsequent host expression maintains a transformed phenotype which has been linked to oncogenesis. HPV DNA testing is primarily used for the detection of high-risk type of HPV infections to screen for cervical cancer. Various HPV testing methods with different principles have been developed and some of them have been approved for clinical use. Major professional organizations have provided recommendation of using HPV testing for cervical cancer screening. In order to prevent HPV infections and subsequent HPV-associated cancers, HPV vaccines have been developed and used in many countries.
Section snippets
Molecular Biology, Pathogenesis, and Epidemiology of HPV
HPVs are nonenveloped viruses, which consist of an icosahedral capsid containing histone-associated dsDNA. About 200 genotypes have been identified to date, which are differentiated by their genetic sequences encoding the outer capsid protein. HPV infects epithelium of skin and mucosal origins and commonly induces benign self-limiting lesions, but is also known to be potentially oncogenic pathogens associated with cervical, anogenital, and oral cancers. HPV infection is currently one of the
Principles and Methods for HPV Testing
There are over about 200 different genotypes of HPV with around 40 of these types able to infect the anogenital mucosa of humans. Of these 40 types, 14 (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) are considered high risk (HR) for the development of cervical cancer and/or precursor legions. HPV-16 is associated with approximately 60% of cervical cancers, while HPV-18 is associated with 15% of cervical cancers. In 2002, guidelines began inclusion of recommendations for
Cervical Cancer Screening
Historically cervical cancer screening recommendations have changed relatively rapidly since the introduction of the Pap test reflecting emerging data and understanding of the pathogenesis of cervical cancer. Prior to 1980 the ACS recommended a Pap test “as part of a regular checkup” [119]. From 1980 to 1987 the recommendation for cervical cancer screening was for annual Pap smears with cervical cytology for women over the age 20 (younger if sexually active) and if two negative Pap tests, this
HPV Vaccines and the Impact on Cervical Cancer Screening
HPV vaccines consist of type-specific HPV L1 proteins that are capable of self-assembly into VLPs. VLPs do not contain vDNA, and thus are noninfectious. The FDA currently licenses three HPV vaccines. Cervarix (GlaxoSmithKline Biologicals, Rixensart, Belgium) is a bivalent vaccine that provides protection against HPV types 16 and 18, which are responsible for approximately 70% of cervical cancer cases. A quadrivalent HPV vaccine, Gardasil (Merck, Kenilworth, NJ) adds protection against HPV types
Acknowledgments
Section 4, “Cervical Cancer Screening,” is adapted from a prior published article in Current Treatment Options in Oncology by M.R.D. and S.F. entitled “Making Sense of Cervical Cancer Screening” [227] with permission of Springer.
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Update on human papillomavirus – Part II: complementary diagnosis, treatment and prophylaxis
2021, Anais Brasileiros de DermatologiaCitation Excerpt :The following tests have been approved by the FDA to evaluate cervical cancer: the Qiagen Hybrid Capture-2, approved in 2003, is a test that identifies 13 types of HR HPV: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68; the Cervista, approved in 2009, identifies 14 types of HR HPVs; the Cobas HPC, approved in 2011, identifies HPV-16, HPV-18 and other 12 types of HR HPVs in a single reaction, and in 2014 the Cobas 4800, a fully automated test, was the first to be approved by the FDA as the first line screening for cervical cancer risk in women aged 25 or older; the Aptima HPV Assay, approved in 2011, focuses on the identification of HPV E6/E7 oncogenes through the detection of messenger RNA of 14 types of HR HPV and, finally, the Onclarity, approved in 2018, also detects the oncogenes E6 and E7 of 14 types of HR HPV. All of these tests show high sensitivity and specificity.17,18 The Brazilian National Health Surveillance Agency, ANVISA, approves most of these tests, in addition to others.19
Prognosis prediction signature of seven immune genes based on HPV status in cervical cancer
2020, International ImmunopharmacologyCitation Excerpt :Therefore, it is urgent to find useful biomarkers to improve the prognosis of patients with CC. Human papillomavirus (HPV), including high-risk HPV (HR-HPV) and low-risk HPV (LR-HPV) [10], mainly causes CC, anogenital cancer, and head and neck squamous cell carcinoma (HNSCC), which accounts for about 5% of all cancers in the world [11,12]. Especially, HR-HPV should be taken more attention because of its close association with the occurrence and development of CC and HNSCC [13,14].
Updates in Cervical Cytology: The 90-Year-Long Journey from Battle Creek to Today
2018, Surgical Pathology ClinicsCitation Excerpt :Additional issues in vaccination revolve around not only access and cost, but social and interpersonal attitudes. Concerns regarding vaccination safety and association with increased incidence of sexually transmitted infections have been mitigated through multiple studies.43 Increased vaccination, however, presents an interesting diagnostic dilemma in cervical cancer screening in that a reduction in the prevalence of high-risk HPV types is expected to cause a decrease in positive predictive value of cervical cancer screening.