Testing for human papillomavirus in cervical cancer screening

Abstract

High-risk human papillomavirus (hrHPV) testing has become an integral component of cervical cancer screening, given that persistent infection with hrHPV was recognized as a significant risk factor for most precancers and cancers of the cervix. Particularly, testing for hrHPV types (in conjunction with cervical cytology) has been approved for primary screening in women over 30 years of age and for cost-effective triaging of equivocal cervical cytology results. HPV was a small double-stranded DNA virus that cannot be cultured in vitro; so, different types of tests have been developed to detect its presence. Various molecular techniques were available for detecting the presence and/or quantity of hrHPV. In this review, the testing options for hrHPV and its surrogates, with an emphasis on those approved by the US Food and Drug Administration (FDA), were detailed. Cancer (Cancer Cytopathol) 2011;119:219-27. V C 2011 American Cancer Society.KEY WORDS: HPV testing, human papillomavirus, cervical cancer screening.High-risk human papillomavirus (hrHPV) testing has become an integral component of cervical cancer screening. Epidemiologic studies provide strong evidence supporting hrHPV infection as a necessary stage in the development of cervical cancer.1-5 Although cervical infection with hrHPV is common, the majority of these cases are self-limited and resolve within 2 years. 6-8 In a small percentage, the infection persists and allows for the overexpression of key HPV oncoprotein-producing genes including E6 and E7. These proteins play an important role in cell cycle dysregulation and promote uncontrolled cell survival and proliferation in a multistep progression that may culminate with invasive carcinoma. 9 With the recognition that persistent infection with hrHPV is a significant risk factor and a necessary precursor for most precancers and cancers of the cervix, hrHPV testing has become an important facet of large-scale screening programs. Particularly, testing for hrHPV types (in conjunction with cervical cytology) has been approved for primary screening in women over 30 years of age and for cost-effective triaging of equivocal cervical cytology results. In this review, the testing options for hrHPV and its surrogates, with an emphasis on those approved by the US Food and Drug Administration (FDA), will be detailed.

Human Papillomavirus Community in Healthy Persons, Defined by Metagenomics Analysis of Human Microbiome Project Shotgun Sequencing Data Sets

“…There are 12 low-risk HPV types that cause genital warts and are rarely associated with cervical cancers. Current HPV detection kits were designed to cover the HPV types present in the cervical region, with an emphasis on detecting high-and low-risk HPV types (51)(52)(53). Our findings indicate that the cervical HPV detection kits may not be appropriate for use in detection of HPV in other organs because of the difference in organ tropisms of HPV types as shown in the phylogenetic analysis and the difference in dominant HPV types between organs (Fig.…”

“…The preclinical and subclinical HPV infections might not develop into a clinical disease under the suppression of a competent immune system. For example, out of the 14 HPV types designated high-risk for cervical cancer by the IARC (48), 10 (types 16,18,39,45,51,52,56,59,66, and 68) were present in the vagina of nine women with no clinical diseases. Some high-risk HPV types were also detected in samples from the skin (types 18, 45, and 58), gut (types 18, 58, and 68), and mouth (type 66) in healthy subjects.…”

Clinical Prediction Based on HPV DNA Testing by Hybrid Capture 2 (HC2) in Combination with Liquid-based Cytology (LBC)

“…HC2 can detect the most common carcinogenic HPV genotypes. The FDA has recommended 1.0 relative light unit for positive result (1 pg HPV DNA per 1 ml of sampling buffer) (Iftner et al, 2003) and use in patients with equivocal cervical cytology results in conjunction with primary routine Pap testing for women over the age of 30 (Nishino et al, 2011). The main limitations are potential cross-reaction with untargeted non-carcinogenic HPV genotypes such as 11, 54 and 66 which would reduce the positive predictive value of HPV testing and clinical specificity, inability to identify specific types, discriminate multiple infections and lack of an internal control to evaluate specimen adequacy (Seme et al, 2006;Castle et al, 2008).…”

Techniques for maximizing the performance of molecular pathology testing: responsibilities of all pathologists

“…The material obtained by scraping from liquid-based smears is a successful source for molecular tests (83)(84)(85)(86)(87)(88)(89)(90)(91). The advantage of liquid-based studies is that they can be easily applied and put into protective fluid after obtaining the sample, which is necessary for the protection of the nucleic acid, immediately.…”