Human papillomavirus genotyping for the eight oncogenic types can improve specificity of HPV testing in women with mildly abnormal Pap results

Abstract

To evaluate whether human papillomavirus (HPV) genotyping for the selected oncogenic HPV types can improve the efficacy of HPV DNA testing in predicting cervical intraepithelial neoplasia (CIN 2/3) in women with mildly abnormal Pap results, we compared HPV DNA testing and HPV genotyping for eight oncogenic types (16, 18, 31, 33, 35, 45, 52 and 58) in Pap specimens with abnormal results (HSIL, 20 cases; LSIL, 42 cases; ASC-US, 94 cases) and follow-up biopsies. Using consensus primer-mediated PCR assays, HPV DNA was detected in 90% (18/20) of HSIL, 95% (40/42) of LSIL and 64% (60/94) of ASC-US cases. HPV DNA positivity was significantly associated with CIN 2/3/carcinoma (Po0.001) in women with ASC-US, but not in women with LSIL (P ¼ 0.52). Of HPV DNA-positive specimens, the eight oncogenic HPV types were detected in 83% of HSIL cases (15/18), 53% of LSIL cases (21/40), and 47% of ASC-US cases (28/60). The eight oncogenic HPV types were significantly associated with CIN 2/3/carcinoma (OR, 10.6; 95% CI, 3.98-28.10; Po0.001), whereas no significant association was observed between the non-eight oncogenic HPV types and CIN 2/3/carcinoma (OR, 2.20; 95%CI, 0.80-6.03; P ¼ 0.125). In women with ASC-US, HPV genotyping for the eight oncogenic types showed higher specificity (81 vs 46%) and positive predictive value (PPV, 44 vs 26%) in predicting CIN 2/3/carcinoma compared to HPV DNA testing. Similarly, in women with LSIL, higher specificity (69 vs 8%) and PPV (62 vs 39%) for predicting CIN 2/3/carcinoma were also observed using HPV genotyping test for the eight oncogenic types compared to HPV DNA testing. Our findings suggested that HPV genotyping for the eight oncogenic types might be useful to improve the efficacy of HPV DNA testing for predicting CIN 2/3/carcinoma in women with mildly abnormal Pap results, which may lead to personalized clinical management with improved patient compliance for follow-up. Modern Pathology (2008Pathology ( ) 21, 1037Pathology ( -1043 doi:10.1038/modpathol.2008 published online 23 May 2008 Keywords: human papillomavirus; HPV; genotyping; HSIL; LSIL; ASCUS Oncogenic HPV infection has been recognized as a primary risk factor responsible for more than 99% of cervical carcinoma and high-grade cervical precancerous lesions, that is, CIN 2/3.1 Persistent oncogenic HPV infection has been considered as the most important factor to determine cervical precancerous lesion progression. 2,3 In the United States, HPV DNA testing in conjunction with Pap cytology test has become standard practice for patient management in gynecology clinics and cervical cancer prevention programs. 4,5 Reflex oncogenic HPV DNA testing using pooled-probes has proved cost effective in the triage of women with atypical squamous cells of under-determined significance (ASC-US).6 Triage of women with low-grade squamous intraepithelial lesions (LSIL) using HPV DNA testing was recently recommended, but only for postmenopausal women. 4 The reason that HPV DNA testing was not recommended initially in the triage of women with LSIL...

Comparison of the performance of the PANArray™ HPV test and DNA chip test for genotyping of human papillomavirus in cervical swabs

“…Furthermore, genotyping for specific oncogenic HPV types has also been shown to increase the positive predictive value and specificity in predicting CIN2/3 and carcinoma in women with ASCUS and LSIL, thus possibly tailoring clinical management of these women 5 . Especially, in the vaccine era, HPV genotyping may be considered useful for assessing the prevalence of specific HPV types and for determining genotype unmasking (i.e., an increase in prevalence of non-vaccine HPV types) in registries and population-based studies.…”

Invader human papillomavirus (HPV) type 16 and 18 assays as adjuncts to HPV screening of cervical papanicolaou smears with atypical squamous cells of undetermined significance

“…These findings are reminiscent of the ALTS trial. 12 In addition, in a recent study that evaluated the presence of 8 selected HR HPV virus types in mildly abnormal Pap smears, Guo et al 22 noted the highest association of !CIN-2 with HPV-16 and HPV-18 in women who had Pap smears with ASC-US.…”

“…Guo et al, 22 studying 8 of the most common 16 Further studies will be needed to address the significance of various values for analytical sensitivity, because the presence of very low HPV DNA levels detectable by highly sensitive assays may not correlate clinically with the development or presence of disease. Because the majority (73%) of our known HR HPV-positive women was negative for HPV-16 and at low risk for !CIN-2, the triage of these women to immediate colposcopy may represent excessive intervention for a relatively low-risk process.…”

Posthysterectomy Cytology Screening

“…This is similar when compared with VAIN. There are many other types of HPV that may result in an abnormal cytologic result, but these may have no real association with neoplasia [13]. Pearce et al [5] analyzed 9,610 vaginal cytologic specimens from patients after hysterectomy.…”