Is HPV DNA testing specificity comparable to that of cytological testing in primary cervical cancer screening? Results of a meta‐analysis of randomized controlled trials

Abstract

Human-papillomavirus (HPV) DNA testing has been proposed as an alternative to primary cervical cancer screening using cytological testing. Review of the evidence shows that available data are conflicting for some aspects. The overall goal of the study is to update the performance of HPV DNA as stand-alone testing in primary cervical cancer screening, focusing particularly on the aspects related to the specificity profile of the HPV DNA testing in respect to cytology. We performed a metaanalysis of randomized controlled clinical trials. Eight articles were included in the meta-analysis. Three outcomes have been investigated: relative detection, relative specificity, and relative positive predictive value (PPV) of HPV DNA testing versus cytology. Overall evaluation of relative detection showed a significantly higher detection of CIN21 and CIN31 for HPV DNA testing versus cytology. Meta-analyses that considered all age groups showed a relative specificity that favored the cytology in detecting both CIN21 and CIN31 lesions whereas, in the ‡30 years' group, specificity of HPV DNA and cytology tests was similar in detecting both CIN21 and CIN31 lesions. Results of the pooled analysis on relative PPV showed a not significantly lower PPV of HPV DNA test over cytology. A main key finding of the study is that in women aged ‡30, has been found an almost overlapping specificity between the two screening tests in detecting CIN2 and above-grade lesions. Therefore, primary screening of cervical cancer by HPV DNA testing appears to offer the right balance between maximum detection of CIN21 and adequate specificity, if performed in the age group ‡30 years.Cervical cancer is the third leading cancer site worldwide among women, 1 and virtually all cases are associated with persistent infection with high-risk serotypes of human papillomavirus (HPV). The infection with HPV is necessary, although not sufficient, for developing cervical cancer. Over 70% of cervical HPV infections clear spontaneously within 24 months without causing lesions. Only a small proportion of infections will persist beyond 2 years.2 The persistent infections with HPV can lead to dysplasia of the transformation zone epithelium of the uterine cervix. This preinvasive lesion, that is known as cervical intraepithelial neoplasia (CIN), represents the main precursor to invasive cervical cancer.Over the last decades, developed countries have observed a dramatic decrease in mortality related to cervical cancer. 3This positive trend is consistently the consequence of the adoption of large-scale screening programs that are based on Papanicolau (Pap) cytology test. Despite this success, the main limitation of Pap test is represented by its low sensitivity and, consequently, high proportion of false-negative tests that require repeating the screening test at relatively short intervals. 4 The recognition of the critical role of HPV in cervical cancer etiology has fostered the achievement of medical advances for prevention of cervical cancer through HPV vaccination and earl...

PAX1 methylation as an auxiliary biomarker for cervical cancer screening: A meta-analysis

“…Nevertheless, the transient nature of age-dependent prevalence of HPV infection suggests that the overall specificity and/or positive predictive value can be compromised [12][13][14]. Only a minute fraction of HPV infections actually progress to cervical neoplasia.…”

Acceptability and feasibility of a community based participatory research project comparing cytology and urine HPV DNA testing for cervical cancer screening in Yap, Federated States of Micronesia

“…HPV DNA testing has proven to be an important adjunct to cervical cytology (Pap) screening for the early detection of precancerous lesions [3]. Recent studies have demonstrated that HPV DNA testing has higher sensitivity than Pap smear testing [4,5]. In March 2014, the U.S. Food and Drug Administration advisory panel recommended that HPV DNA testing could serve as the primary tool for cervical cancer screening.…”

Prevención del cáncer cérvico-uterino en Chile: Mucha vacuna y poco Papanicolau

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“…Meta-análisis comparativos entre el diagnóstico de infección por VPH usando métodos moleculares versus citología convencional indican que en mujeres > 30 años, estos nuevos métodos permitirían detectar un mayor número de casos de NIE tipo II y III con la misma especificidad que la citología y podrían ser justificados en este segmento 10 . Sin embargo, hasta ahora estas nuevas metodologías se han aplicado y evaluado principalmente en países desarrollados y su costo es mayor que el del Papanicolau.…”

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