HPV status in women with high-grade dysplasia on cervical biopsy and preceding negative HPV tests

Ge, Yimin; Mody, Roxanne; Olsen, Randall J.; Zhou, Haijun; Luna, Eric; Armylagos, Donna; Puntachart, Natu; Hendrickson, Heather; Schwartz, Mary R.; Mody, Dina R.

doi:10.1016/j.jasc.2019.01.001

Cited by 17 publications

(14 citation statements)

References 34 publications

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“…7,8 HPV-negative HSIL or cervical cancer cases have been reported with both HPV DNA and mRNA testing. [22][23][24][25][26] In this study, hrHPV-negative HSIL accounted for ~4.8% of HSIL cytology, and this result is consistent with reporting rates of ~5% to 8% in earlier studies. 8,27,28 Explanations for the hrHPV-negative HSIL results have included inadequate sampling, interference material, technical errors, lesion regression, low viral loads, non-hrHPV infections, and a loss of L1 gene expression.…”

Section: Discussionsupporting

confidence: 92%

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Aptima HPV messenger RNA testing and histopathologic follow‐up in women with HSIL cytology: A study emphasizing additional review of HPV‐negative cases

Austin

et al. 2021

Cancer Cytopathology

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Background High‐risk human papillomavirus (hrHPV) messenger RNA (mRNA) testing, the Food and Drug Administration–approved testing platform since 2013, has been increasing as a cervical screening alternative to hrHPV DNA testing methods. This study reports the largest routine clinical follow‐up study reported to date of hrHPV mRNA cotesting and histopathologic follow‐up results for women with high‐grade squamous intraepithelial lesion (HSIL) cytology results. Methods HSIL Papanicolaou test results for women cotested with Aptima hrHPV mRNA testing between June 2015 and November 2020 were analyzed along with recorded histopathologic follow‐up results within 6 months of screening. Results Aptima hrHPV mRNA–positive results were reported for 95.2% of the cotested HSIL cytology cases (905 of 951). Histopathologic cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed on follow‐up in 538 of 701 hrHPV mRNA–positive cases (76.8%) and in 15 of 36 hrHPV mRNA–negative cases (41.7%). Additional reviews of the hrHPV mRNA–negative HSIL cases showed variable interpretations, and confirmatory blinded‐review interpretations of HSIL or atypical squamous cells, cannot exclude high‐grade squamous intraepithelial lesion were more likely in cases with histopathologic CIN2+ (77.5% [93 of 120]) than those with cervical intraepithelial neoplasia grade 1 or negative findings (63.1% [101 of 160]; P < .01). Conclusions This large routine‐clinical‐practice study confirms the previously reported high sensitivity of hrHPV mRNA testing for the detection of high‐grade cervical dysplasia and cervical cancers. The blinded‐review findings indicate that additional cytology review may be helpful for confirming an interpretation of HSIL in daily practice, especially for hrHPV‐negative HSIL cases.

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Section: Discussionsupporting

confidence: 92%

“…HPV‐negative HSIL or cervical cancer cases have been reported with both HPV DNA and mRNA testing 22‐26 . In this study, hrHPV‐negative HSIL accounted for ~4.8% of HSIL cytology, and this result is consistent with reporting rates of ~5% to 8% in earlier studies 8,27,28 .…”

Section: Discussionsupporting

confidence: 90%

Aptima HPV messenger RNA testing and histopathologic follow‐up in women with HSIL cytology: A study emphasizing additional review of HPV‐negative cases

Austin

et al. 2021

Cancer Cytopathology

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“…Enrolment of patients started in November 2018 and closed in April 2020. Because a negative HPV test is very rare in patients with HSIL and since, according to our guidelines, we do not test patients for high-risk HPV in cases of HSIL, the test was not performed prior to inclusion in the study [29]. Inclusion criteria were as follows: (i) newly diagnosed and previously untreated HSIL in women aged from 18 to 35 years or up to 40 years in case of nulliparity; (ii) adequate colposcopy (i.e., fully visible lesion and transformation zone); (iii) negative pregnancy test; (iv) safe contraception; and (v) freely given and signed informed consent.…”

Section: Methodsmentioning

confidence: 99%

Comparison of Conservative Treatment of Cervical Intraepithelial Lesions with Imiquimod with Standard Excisional Technique Using LLETZ: A Randomized Controlled Trial

Cokan

Pakiž

Serdinšek

et al. 2021

JCM

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(1) Background: There are limited data on the success of conservative treatment of high-grade cervical squamous intraepithelial lesions (HSIL) with imiquimod directly compared to standard of treatment with LLETZ. (2) Methods: Patients aged 18–40 with histological HSIL (with high-grade cervical intraepithelial neoplasia, CIN2p16+ and CIN3), were randomly assigned to treatment with imiquimod or LLETZ. The primary outcome was defined as the absence of HSIL after either treatment modality. The secondary outcomes were the occurrence of side effects. (3) Results: 52 patients were allocated in each group and were similar regarding baseline characteristics. In the imiquimod group, 82.7% of patients completed treatment, which was successful in 51.9%. All patients in the LLETZ group completed treatment, which was successful in 92.3% (p < 0.001). In the subgroup of CIN2p16+ patients, treatment with imiquimod was not inferior to LLETZ (73.9% vs. 84.2%, p = 0.477). During and after treatment, no cases of progression to cancer were observed. Side effects and severe side effects (local and systemic) were more prevalent in the imiquimod than in the LLETZ group (88.5% vs. 44.2% (p-value < 0.001) and 51.9% vs. 13.5% (p-value < 0.001), respectively). (4) Conclusion: Generally, in patients with HSIL, LLETZ remains the gold standard of treatment. However, in a subgroup analysis of patients with CIN2p16+, the success rate was comparable between the two treatment modalities. Due to the prevalence of side effects, the treatment compliance with imiquimod use may, however, present a clinically important issue.

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“…To study the L1 genetic variability of HPV81, we selected a subset of HPV81 SIs (n = 6) and a subset of HPV81 MIs (n = 4). HPV81 was chosen because it has been frequently observed in association with LSIL and HSIL grade lesions (Minosse et al, 2010;Annunziata et al, 2018;Ge et al, 2019), though it is considered a LR type, and little information is available on its genetic variability. The PCR to amplify the L1 region was based on two PCRs that were combined to obtain the full length of the L1 sequences.…”

Section: L1 and L2 Sequencesmentioning

confidence: 99%

Human Papillomavirus Infections in Cervical Samples From HIV-Positive Women: Evaluation of the Presence of the Nonavalent HPV Genotypes and Genetic Diversity

et al. 2020

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Non-nonavalent vaccine (9v) Human papillomavirus (HPV) types have been shown to have high prevalence among HIV-positive women. Here, 1444 cervical samples were tested for HPV DNA positivity. Co-infections of the 9v HPV types with other HPV types were evaluated. The HPV81 L1 and L2 genes were used to investigate the genetic variability of antigenic epitopes. HPV-positive samples were genotyped using the HPVCLART2 assay. The L1 and L2 protein sequences were analyzed using a self-optimized prediction method to predict their secondary structure. Co-occurrence probabilities of the 9v HPV types were calculated. Non9v types represented 49% of the HPV infections; 31.2% of the non9v HPV types were among the low-grade squamous intraepithelial lesion samples, and 27.3% among the high-grade squamous intraepithelial lesion samples, and several genotypes were low risk. The co-occurrence of 9v HPV types with the other genotypes was not correlated with the filogenetic distance. HPV81 showed an amino-acid substitution within the BC loop (N75Q) and the FGb loop (T315N). In the L2 protein, all of the mutations were located outside antigenic sites. The weak cross-protection of the 9v types suggests the relevance of a sustainable and effective screening program, which should be implemented by HPV DNA testing that does not include only high-risk types.

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HPV status in women with high-grade dysplasia on cervical biopsy and preceding negative HPV tests

Cited by 17 publications

References 34 publications

Aptima HPV messenger RNA testing and histopathologic follow‐up in women with HSIL cytology: A study emphasizing additional review of HPV‐negative cases

Aptima HPV messenger RNA testing and histopathologic follow‐up in women with HSIL cytology: A study emphasizing additional review of HPV‐negative cases

Comparison of Conservative Treatment of Cervical Intraepithelial Lesions with Imiquimod with Standard Excisional Technique Using LLETZ: A Randomized Controlled Trial

Human Papillomavirus Infections in Cervical Samples From HIV-Positive Women: Evaluation of the Presence of the Nonavalent HPV Genotypes and Genetic Diversity

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