Comparison of Seegene Anyplex II HPV28 assay with BD Onclarity HPV assay for human papillomavirus genotyping

Classified as probably not a substantial claim.

The BD Onclarity HPV assay detects six individual genotypes (HPV 16, 18, 31, 45, 51, and 52) and three groups comprising eight HPV genotypes (HPV 33 and 58; HPV 56, 59, and 66; and HPV 35, 39, and 68).

“Onclarity can detect six individual genotypes (HPV 16, 18, 31, 45, 51, and 52) and three distinct groups comprising a total of eight HPV genotypes (HPV 33 and 58; HPV 56, 59, and 66; and HPV 35, 39, and 68) [11].”

• cites [11] PE Castle, 2011, Evaluation of a New DNA Test for Detection of Carcinogenic Human Papillomavirus, Journal of Clinical Microbiology sourceDisputed

  Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Clinical validation of Onclarity and Anyplex has been performed in previous studies according to international guidelines.

“Although clinical validation of Onclarity and Anyplex has been performed in previous studies according to the international guidelines for human papillomavirus DNA testing [13–17]”

• cites [13] JH Bonde, 2020, Clinical and Analytical Performance of the BD Onclarity HPV Assay with SurePath Screening Samples from the Danish Cervical Screening Program Using the VALGENT Framework, J Clin Microbiol sourcePartly supported

  The Discussion explicitly says that previous studies validated Onclarity using the international guidelines. The References list an Anyplex clinical evaluation within the VALGENT-3 framework, but our copy does not say that Anyplex was validated according to those international guidelines. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [14] DM Ejegod, 2016, Clinical and analytical performance of the BD Onclarity HPV assay for detection of CIN2+ lesions on SurePath samples., Papillomavirus Res. sourcePartly supported

  The Discussion (Comparison to the literature; page not provided) reports earlier clinical performance studies of Onclarity, and the References list prior Onclarity clinical-validation studies. This paper does not address Anyplex or establish that validation of both assays followed international guidelines. It also cautions that its own referral-population study cannot assess primary-screening performance. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [15] C Estrade, 2014, Comparison of Seegene Anyplex II HPV28 with the PGMY-CHUV assay for human papillomavirus genotyping, J Clin Microbiol sourceDisputed

  The Discussion says Anyplex II HPV28 is suitable as an adjunct to a clinically validated test and that its readout ought to be evaluated for primary cervical cancer screening—not that it had already been clinically validated under international guidelines. The introduction discusses guideline-based validation of Abbott and Roche tests, not Anyplex or Onclarity; our copy does not address Onclarity. (LLM, conf=0.84)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured
• cites [16] A Latsuzbaia, 2016, Analytical performance evaluation of Anyplex II HPV28 and Euroarray HPV for genotyping of cervical samples, Diagn Microbiol Infect Dis sourceNot checked — no full text of the source
• cites [17] C Pasquier, 2017, Comparison of Cobas® HPV and Anyplex™ II HPV28 assays for detecting and genotyping human papillomavirus, Diagn Microbiol Infect Dis sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

HPV-based cervical cancer screening has superior sensitivity and negative predictive value compared with cytology screening tests.

“HPV-based cervical cancer screening is widely used and has superior sensitivity and negative predictive value compared with cytology screening tests [7].”

• cites [7] G Koliopoulos, 2017, Cytology versus HPV testing for cervical cancer screening in the general population, The Cochrane database of systematic reviews sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

The majority of cervical cancers and their precursor lesions are derived from HPV infections.

“The majority of cervical cancers and their precursor lesions are derived from human papillomavirus (HPV) infections [1].”

• cites [1] N Muñoz, 2003, Epidemiologic classification of human papillomavirus types associated with cervical cancer, New England journal of medicine sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The Seegene Anyplex II HPV28 assay is designed to detect 14 hrHPV types, five possible hrHPV types, and nine low-risk HPV types.

“It has been specifically designed to simultaneously detect 14 hrHPV types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68), five possible hrHPV types (HPV26, 53, 69, 73, and 82), and nine low-risk (lr)HPV types (HPV 6, 11, 40, 42, 43, 44, 53, 54, and 70) [12].”

• cites [12] I Baasland, 2019, Clinical performance of Anyplex II HPV28 by human papillomavirus type and viral load in a referral population., PLoS One sourcePartly supported

  The Materials and methods > HPV testing passage confirms that Anyplex II HPV28 detects 14 hrHPV types, five possible hrHPV types, and nine low-risk types, and its first two type lists match the citing sentence. The citing sentence’s low-risk list does not match: it names HPV53, which the paper lists as a possible hrHPV type, and omits low-risk HPV61. (LLM, conf=0.94)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

14 anogenital HPVs are categorized as high-risk HPV types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68).

“14 anogenital HPVs have been categorized as high-risk HPV (hrHPV) types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) [3].”

• cites [3] EM Burd, 2003, Human papillomavirus and cervical cancer, Clin Microbiol Rev sourcePartly supported

  The Introduction categorizes all 14 listed types as high-risk, and the HPV DNA Detection section lists those exact 14 as targets of high-risk type-specific PCR assays. But the Introduction also includes HPV 34 and 70 in its high-risk category, so it does not support a total of only 14 high-risk types. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

HPV genotyping is needed to triage patients for cervical cancer screening.

“HPV genotyping is also needed to triage patients for cervical cancer screening [25]”

• cites [25] JH Bonde, 2020, Clinical Utility of Human Papillomavirus Genotyping in Cervical Cancer Screening: A Systematic Review., J Low Genit Tract Dis sourcePartly supported

  The Conclusions (page not supplied) say genotype information can be used to triage HPV-positive women. They do not say genotyping is needed for cervical cancer screening; the Discussion says cytology will remain the triage method for HPV-positive samples for the foreseeable future. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Onclarity is an FDA-approved HPV genotyping test widely used for cervical cancer screening, including at several major hospitals in South Korea.

“Onclarity is an FDA-approved HPV genotyping test widely used for cervical cancer screening including several major hospitals at South Korea [29].”

• cites [29] MS Kim, 2020, Utility of Human Papillomavirus Testing for Cervical Cancer Screening in Korea., International Journal of Environmental Research and Public Health sourcePartly supported

  Methods §2.5 identifies BD Onclarity as an HPV genotyping assay, and Methods §2.1 reports its use in cervical screening at Samsung Changwon Hospital in Korea. The paper does not establish FDA approval, widespread use, or use at several major South Korean hospitals; its study draws records from one hospital. Page numbers were not available in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Onclarity targets the E6/E7 gene of HPV, whereas Anyplex targets the L1 gene.

“Although Onclarity targets the E6/E7 gene of HPV [14], Anyplex targets the L1 gene [36].”

• cites [14] DM Ejegod, 2016, Clinical and analytical performance of the BD Onclarity HPV assay for detection of CIN2+ lesions on SurePath samples., Papillomavirus Res. sourceSupported
• cites [36] J Bonde, 2018, The Valgent4 protocol: Robust analytical and clinical validation of 11 HPV assays with genotyping on cervical samples collected in SurePath medium., J Clin Virol sourceCould not verify

  Table 1 lists both BD Onclarity and Seegene Anyplex assays and gives their amplicon lengths, but not the HPV genes they target. Sections 3.9.1 and 3.9.3 describe Onclarity testing without identifying an E6/E7 target. Searches for L1 and E6/E7 found no passage in our copy establishing the claimed targets. (LLM, conf=0.77)

  Experimental — accuracy not yet measured

May combine two claims.

Patients tend to visit different hospitals and may repetitively undergo similar HPV genotyping assays because of the relatively lower costs of national health insurance in Korea.

“Meanwhile, patients tend to visit different hospitals and may repetitively undergo similar HPV genotyping assays due to relatively lower costs of national health insurance in Korea [33–35].”

• cites [33] F Ng, 2020 sourceNot checked — no full text of the source
• cites [34] JY Shin, 2011, Overlapping medication associated with healthcare switching among Korean elderly diabetic patients, Journal of Korean medical science sourcePartly supported

  The Introduction says patients in Korea can visit any healthcare provider, and the Results document switching between institutions among elderly diabetic patients. The paper does not address repeated HPV genotyping assays or show that relatively low National Health Insurance costs cause such visits. Page numbers are not available in our copy. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [35] K Kim, 2017, Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications., Journal of Hospital Infection sourcePartly supported

  The Discussion (page not available) describes “doctor shopping” in South Korea as seeking treatment at various hospitals for the same ailment, supporting the hospital-visits portion. It does not say that patients repeatedly undergo HPV genotyping or that lower national-health-insurance costs cause those visits. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

HPV genotyping is needed to establish the impact of HPV vaccination programs.

“establish the impact of HPV vaccination programs [27, 28]”

• cites [27] M Paz-Zulueta, 2018, Prevalence of high-risk HPV genotypes, categorised by their quadrivalent and nine-valent HPV vaccination coverage, and the genotype association with high-grade lesions, BMC cancer sourcePartly supported

  The Discussion (page unavailable) says that HPV genotype prevalence in unvaccinated women can be used to estimate the potential impact of quadrivalent and nine-valent vaccines. It does not say genotyping is necessary to establish the observed impact of vaccination programs; it also cautions against generalizing its estimates to the general population. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites [28] KRM Leite, 2020, HPV Genotype Prevalence and Success of Vaccination to Prevent Cervical Cancer., Acta Cytologica sourceNot checked — no full text of the source

May combine two claims.

Anyplex is widely used for cervical cancer screening in South Korea, including at the authors' hospital.

“Anyplex is also widely used for cervical cancer screening in South Korea, including at our hospital [30–32].”

• cites [30] KA So, 2016, Human Papillomavirus Prevalence and Type Distribution Among 968 Women in South Korea., J Cancer Prev sourcePartly supported

  The Materials and Methods (Study population; Human papillomavirus DNA testing, pages not provided) document use of Anyplex for HPV testing at Korea University Guro Hospital. The paper does not establish that Anyplex is widely used for cervical cancer screening across South Korea or that it is used at the citing authors’ hospital. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [31] EH Nah, 2017, Human Papillomavirus Genotype Distribution Among 18,815 Women in 13 Korean Cities and Relationship With Cervical Cytology Findings., Ann Lab Med. sourceSupported
• cites [32] YT Ouh, 2018, Prevalence of human papillomavirus genotypes and precancerous cervical lesions in a screening population in the Republic of Korea, 2014–2016, J Gynecol Oncol sourcePartly supported

  The Methods (HPV DNA testing; page unavailable) report that Anyplex was used on 7,331 samples at a Korean screening organization in 2016. This establishes use in a South Korean screening setting, but not that Anyplex was widely used nationwide or used at the citing authors’ hospital. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women of 30 years and older are widely accepted and used to validate HPV assays.

“Currently, “Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women of 30 years and older” [21] are widely accepted and used to validate HPV assays.”

• cites [21] CJ Meijer, 2009, Guidelines for human papillomavirus DNA test requirements for primary cervical cancer screening in women 30 years and older, International journal of cancer sourcePartly supported

  The “Validation guidelines for candidate HPV assays” section sets out criteria for validating HPV tests, supporting the identification of this paper as a source of validation guidelines. But the “Laboratory guidelines for HPV testing” section calls them a proposal intended to achieve international consensus; it does not establish that they were already widely accepted or widely used to validate assays. Page numbers are unavailable in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Onclarity has an amplification target range from 79 to 137 base pairs, whereas Anyplex has a target range of approximately 150 base pairs.

“Moreover, Onclarity has an amplification target range from 79 to 137 base pairs, whereas Anyplex has a target range of ~150 base pairs [36].”

• cites [36] J Bonde, 2018, The Valgent4 protocol: Robust analytical and clinical validation of 11 HPV assays with genotyping on cervical samples collected in SurePath medium., J Clin Virol sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

HPV16 and HPV18 constitute more than 70% of cervical cancers.

“Although HPV16 and HPV18 constitute >70% of cervical cancers [3, 22]”

• cites [3] EM Burd, 2003, Human papillomavirus and cervical cancer, Clin Microbiol Rev sourcePartly supported

  The Introduction says HPV16 accounts for about half of cervical cancer cases in the United States and Europe, while HPV18, HPV31, and HPV45 together account for another 25–30%. It does not assign that additional share to HPV18 alone or establish that HPV16 and HPV18 together exceed 70%. (LLM, conf=0.89)

  Experimental — accuracy not yet measured
• cites [22] S de Sanjose, 2013, Age-specific occurrence of HPV16- and HPV18-related cervical cancer, Cancer Epidemiol Biomarkers Prev sourceSupported

Classified as probably not a substantial claim.

Previous studies suggest that a wider range of HPV genotyping may confer additional clinical benefits.

“previous studies suggest that a wider range of HPV genotyping may confer additional clinical benefits [23, 24]”

• cites [23] CL Trimble, 2005, Spontaneous regression of high-grade cervical dysplasia: effects of human papillomavirus type and HLA phenotype, Clin Cancer Res sourcePartly supported

  The Results report different regression rates for HPV16-related types and other HPV types in women with CIN2/3, and the Discussion suggests that future trials may need HPV-based stratification if the findings are validated. This supports a possible prognostic use for broader genotyping, but the paper does not show that expanding genotyping provides clinical benefits in patient care. (LLM, conf=0.82)

  Experimental — accuracy not yet measured
• cites [24] K Elfgren, 2017, Management of women with human papillomavirus persistence: long-term follow-up of a randomized clinical trial., Am J Obstet Gynecol sourcePartly supported

  The Results report different CIN2+ risks for persistent HPV types, and the Discussion suggests prioritizing women with persistent HPV16 (page not available in our copy). This supports a potential clinical use for type-specific information, but the paper does not evaluate whether genotyping a wider range of HPV types confers additional benefits. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

HPV genotyping is needed to distinguish transient HPV infections from permanent HPV infections.

“distinguish transient HPV infections from permanent HPV infections [26]”

• cites [26] M Jentschke, 2012, Importance of HPV Genotyping for the Screening, Therapy and Management of Cervical Neoplasias., Geburtshilfe Frauenheilkd. sourceSupported

May combine two claims.

From 592 NILM cases, Onclarity determined 368 to be hrHPV negative, whereas Anyplex determined 328 to be hrHPV negative.

“From a total of 592 NILM cases, Onclarity determined 368 cases to be hrHPV negative, whereas Anyplex determined 328 cases to be hrHPV negative.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The hrHPV detection rate was highest for women aged ≥60 years with both Onclarity (59.8%) and Anyplex (64.7%).

“The hrHPV detection rate was highest for women aged ≥60 years with both Onclarity (59.8%) and Anyplex (64.7%).”

May combine two claims.

Kappa values for concordance between Anyplex and Onclarity were excellent for HPV 16, 18, 31, 45, 51, 52, 35/39/68 and 56/59/66, and good for HPV 33/58 (kappa 0.73).

“The kappa values were excellent for HPV 16, 18, 31, 45, 51, 52, 35/39/68, and 56/59/66 and good for HPV 33/58 (kappa value: 0.73).”

May combine two claims.

Agreement between Anyplex and Onclarity for the 14 hrHPV genotypes combined was 90.1%, with a kappa value of 0.8.

“The agreement for the 14 hrHPV combined was 90.1% (kappa value: 0.8) (Table 5).”

May combine two claims.

In NFM samples (N = 592), specificity was 96.3% (95% CI 93.7-98.1) for Onclarity and 85.9% (95% CI 81.9-89.3) for Anyplex.

“| NFM (N = 592) | Total | 264 | 328 | 592 | Specificity 96.3% (CI: 93.7–98.1) | Specificity 85.9% (CI: 81.9–89.3) |”

• Also stated in: § Discussion · plain

  “The specificity of Anyplex was somewhat lower than that of Onclarity for the detection of NILM.”

May combine two claims.

Among ≥CIN2 cases at ≥2+ viral load, six (6/72) were negative for hrHPV by Onclarity and three (3/72) were negative by Anyplex.

“Using the Onclarity assay, six ≥CIN 2 cases were negative for hrHPV (6/72). Using Anyplex, three cases were negative for hrHPV (3/72) (HPV infections ≥2+ (medium) viral load).”

May combine two claims.

For ≥CIN3 lesions (N = 59), sensitivity was 94.6% (95% CI 85.1-98.9) for Onclarity and 100.0% (95% CI 93.3-100.0) for Anyplex.

“| ≥CIN3 (N = 59) | Total | 56 | 3 | 59 | Sensitivity 94.6% (CI: 85.1–98.9) | Sensitivity 100.0% (CI: 93.3–100.0) |”

May combine two claims.

Reporting all HPV infections with 1+ to 3+ viral load yielded only a small increase in detection sensitivity for ≥CIN2 lesions, whereas specificity decreased significantly.

“In this study, reporting all HPV infections with 1+ to 3+ viral load yielded only a small increase in detection sensitivity for ≥CIN 2 lesions, whereas the specificity decreased significantly.”

May combine two claims.

For HPV 33/58, agreement between Onclarity and Anyplex (≥2+ viral load) was 95.1% with a kappa value of 0.73.

“| 33/58 | 71 (7.7%) | 110 (12.0%) | 68 | 3 | 42 | 807 | 95.1 | 0.73 |”

May combine two claims.

Full genotyping with Anyplex might confer additional benefits to patients with ≥CIN2, although the difference is small.

“Full genotyping with Anyplex might confer additional benefits to patients with ≥CIN 2, although the difference is small.”

• AssumptionRests on an assumption: HPV genotyping assays are useful for triage in cervical cancer screening and for evaluation of HPV vaccination effects.

Classified as probably not a substantial claim. May combine two claims.

Pathological diagnoses of tissue specimens were independently reviewed by two gynecological pathologists in a blinded manner, and discrepant results were repeatedly reviewed until consensus was reached.

“Pathological diagnoses of the tissue specimens were independently reviewed by two gynecological pathologists—JYP and NJP—in a blinded manner. Cases with discrepant results were repeatedly reviewed until a consensus was reached.”

May combine two claims.

Both assays demonstrated excellent HPV DNA genotyping concordance, except for HPV 33/58.

“Both tests demonstrated excellent HPV DNA genotyping concordance, except for HPV 33/58.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

This is the first study to directly compare the clinical performance and genotyping capabilities of Anyplex and Onclarity.

“To the best of our knowledge, this is the first study that directly compares the clinical performance and genotyping capabilities of Anyplex and Onclarity.”

Classified as probably not a substantial claim.

Onclarity only provides information on hrHPVs.

“As Onclarity only provides information on the hrHPVs”

Classified as probably not a substantial claim.

Measuring HPV infections only at the level of positive or negative cannot provide information about the individual HPV genotype.

“Measuring HPV infections only at the level of “positive or negative” cannot provide information about the individual HPV genotype.”

Classified as probably not a substantial claim.

These HPV assay validation guidelines primarily focus on the overall ability of HPV assays to detect clinically relevant hrHPV infections.

“However, these guidelines primarily focus on the overall ability of HPV assays to detect clinically relevant hrHPV infections.”

May combine two claims.

Anyplex may confer additional benefits in the management of patients with ≥CIN2 lesions, although the difference from Onclarity is small.

“Thus, Anyplex may confer additional benefits in the management of patients with ≥CIN 2 lesion, although the difference with Onclarity is small.”

Classified as probably not a substantial claim.

Anyplex offers complete genotyping for 28 HPVs, including hrHPVs, possible hrHPVs and lrHPVs.

“Anyplex offers complete genotyping for 28 HPVs including hrHPVs, possible hrHPVs, and lrHPVs.”

Classified as probably not a substantial claim. May combine two claims.

A comparison of the clinical performance of these widely used tests may provide consistent information about HPV infection status and avoid redundant genotyping tests.

“Therefore, a comparison of the clinical performance of these widely used tests may provide consistent information with regard to HPV infection status and avoid redundant genotyping tests.”

May combine two claims.

Onclarity detects HPV 33/58, 56/59/66 and 35/39/68 in three bulk groups, whereas Anyplex identifies all HPV genotypes individually.

“Although Onclarity detects these genotypes in three bulk groups, Anyplex identifies all HPV genotypes individually.”

May combine two claims.

The study sample was drawn from a tertiary referral hospital, with many patients visiting because of abnormal cytology, biopsy or HPV genotyping test results, which might have influenced the specificity of the Anyplex and Onclarity assays in this study.

“Furthermore, the study sample was from a tertiary referral hospital, many patients visited the hospital due to the abnormal cytology, biopsy, or HPV genotyping test results. This might have influenced the specificity of the Anyplex and Onclarity assays in this study.”

Classified as probably not a substantial claim.

The study did not perform an additional reference genotyping assay such as HC2 or GP5+/6+ PCR to estimate the accuracy of the HPV genotyping tests.

“First, we did not perform the additional reference genotyping assay such as HC2 or GP5+/6+ PCR to estimate the accuracy of the HPV genotyping tests.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Onclarity can detect 14 hrHPV genotypes: HPV 16, 18, 31, 45, 51, 52, 33/58, 56/59/66 and 35/39/68.

“It can detect 14 hrHPV genotypes (HPV 16, 18, 31, 45, 51, 52, 33/ 58, 56/59/66, and 35/39/68).”

The quote only partly states this claim.

The relatively low specificity of Anyplex compared with Onclarity can be partially explained by the high HPV prevalence in the study cohort, which was drawn from a tertiary hospital referral population rather than a routine screening population.

“Thus, the high prevalence of HPV infection in the study cohort might have affected the specificity of the Anyplex assays.”

• Also stated in: § Discussion · plain

  “As our sample was drawn from the patient records of a tertiary hospital, the majority of the patients in our study were referred to the hospital due to abnormal cytology, biopsy, or HPV genotyping results obtained at a local clinic rather than for routine screening purposes.”