Abstract
BackgroundHuman Papilloma Virus (HPV) DNA tests are highly sensitive and can triage women with mild lesions, improving the prognosis and diagnosis of cervical lesions. However, additional efficient strategies should be developed to improve the specificity of these tests.MethodsThis study aimed to evaluate the clinical value of HPV DNA load in improving the diagnosis and prognosis of cervical lesions by p16/Ki-67 testing. Histological samples were collected from 350 women with HR-HPV genotyping and analyzed by qRT-PCR. Immunohistochemical staining was used to assess p16 and Ki-67 expression and clinical performance characteristics were calculated.ResultsOf the cases, 271 had detectable HR-HPV infection, in which HPV-16 was most prevalent (52.0%), followed by HPV-58 (22.5%). P16/Ki-67-positivity increased with histological severity but not for HR-HPV infection. Amongst the 13 HR-HPV genotypes, only HPV-16 (P = 0.016) and HPV-58 (P = 0.004) viral loads significantly correlated with lesion severity. The P16/Ki-67/HPV DNA load co-test indicated an increased sensitivity for the detection of cervical intraepithelial neoplasia (CIN) lesions compared to p16/Ki-67 staining in HPV-16 and/or 58 positive cases. Viral load did not improve the sensitivity of p16/Ki-67 co-test in non-HPV-16 or 58 positive cases. The clinical performance of the p16/Ki-67/HPV DNA load co-test was limited for the prediction of the outcome of CIN1 lesions. However, amongst the 12 HPV-16 and/or 58 positive CIN2 cases in which return visit results were obtained, the behavior of the lesions could be predicted, with a sensitivity, specificity, positive prediction rate (PPV), and negative prediction rate (NPV) of 0.667, 1, 1 and 0.5, respectively.ConclusionCombination of the assessment of HPV DNA load with the intensity of p16 and Ki-67 staining could increase the sensitivity of CIN lesion diagnosis and predict the outcome of CIN2 in patients with a HPV-16 and/or 58 infection.
Highlights
Human papillomavirus (HPV) is a major cause of cervical cancer (CCa) and its screening can improve the diagnosis of both CCa and precancerous lesions [1, 2]
The coexpression of p16 and Ki-67 was developed as an auxiliary marker of cervical precancers [11, 12], but a series of studies reported that an increased risk of highgrade cervical intraepithelial neoplasia (CIN) or CCa is associated with high Human Papilloma Virus (HPV) DNA loads [15, 16], suggesting that HPV is a marker to predict cervical neoplasia
We found that the combination of HPV DNA load and p16/Ki-67 staining could effectively predict the outcome of CIN2 lesions in patients infected with HPV-16 and/or 58
Summary
Human papillomavirus (HPV) is a major cause of cervical cancer (CCa) and its screening can improve the diagnosis of both CCa and precancerous lesions [1, 2]. HPV DNA tests are highly sensitive and can triage women with low-grade or equivocal cytological abnormalities, improving prognosis assessments, and increasing the diagnostic accuracy of cervical intraepithelial neoplasia (CIN) lesions [3]. The specificity of HPV assessments for precancerous CCa is poor as the majority of HPV infections are naturally cleared [4]. More specific molecular markers of CCa have been identified based on studies of HPV-induced carcinogenesis. Human Papilloma Virus (HPV) DNA tests are highly sensitive and can triage women with mild lesions, improving the prognosis and diagnosis of cervical lesions. Additional efficient strategies should be developed to improve the specificity of these tests
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