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FDA-APPROVED MOLECULAR TESTS USED TO DEFINE HUMAN PAPILLOMAVIRUS (HPV) INFECTIONS WHICH CAUSE CERVIX CANCER

Year 2023, Volume: 45 Issue: 1, 1 - 11, 31.03.2023

Abdulhamit Çalı Rukiye Aslan Cem Çelik Ahmet Alim

https://doi.org/10.7197/cmj.1187503

Abstract

Human papillomavirus (HPV) is a non-enveloped, commonly sexually transmitted virus with icosahedral symmetry and double-stranded circular DNA. Its genome, which is about 8 kb in size, encodes early genes (E1-8) and two late structural capsid genes (L1 and L2). Among the genes that play a role in viral pathogenesis, L1, E6, and E7 genes frequently exist. The E6 and E7 viral genes have a significant role in apoptosis inhibition, viral spread, development of squamous intraepithelial lesion (SIL), cell immortalization, neoplastic transformation, and invasive cancer.
Demonstration of the relationship between cervical cancer and HPV infections has led to increased interest in this subject and the classification of some HPV genotypes in the high-risk group (HR-HPV) for cervical cancer. Numerous commercial molecular tests have been developed for the identification of HPV genotypes involving different approaches. HPV molecular tests approved by the US Food and Drug Administration (FDA) include Hybrid Capture® 2 (HC2), Cervista™, cobas®, Aptima®, and BD Onclarity™. This article reviews the methodologies, limitations, and commonalities of five FDA-approved tests. The HC2 and Cervista™ tests use non-PCR-based signal amplification methods, while the cobas® and BD Onclarity™ tests use PCR-based target amplification methods. On the other hand, the Aptima® test uses the mRNA transcriptional mediated amplification (TMA) method.
Each of these methods used in the diagnosis and follow-up of HPV has its strengths and weaknesses. These HPV molecular tests have high sensitivity and specificity. They are also more automated and repeatable than cytological methods. In addition to these advantages, there are also several limitations. Because of these limitations, molecular tests are no more perfect than cytological tests. This situation shows that these tests should not be used alone in the evaluation of HPV infections and cancer identification. On the contrary, HPV test results should be correlated with cytology or biopsy findings.

Keywords

Cervical canser Human papillomavirüs HPV Molecular diagnosis

References

  • 1Ursu RG, Damian C, Porumb-Andrese E, et al. Merkel Cell Polyoma Virus and Cutaneous Human Papillomavirus Types in Skin Cancers: Optimal Detection Assays, Pathogenic Mechanisms, and Therapeutic Vaccination. Pathogens. 2022;11(4).
  • Ryan KJ. (Us AD, Başustaoğlu A, eds.). Sherris Tibbi̇ Mi̇krobi̇yoloji̇. Yedinci Baskı. Ankara. Hipokrat Yayınevi; 2019.
  • Taberna M, Mena M, Pavón MA, et al. Human papillomavirus-related oropharyngeal cancer. Ann Oncol. 2017;28(10):2386-2398.
  • Şahiner F. Genital insan papillomavirus enfeksiyonlarının moleküler tanısında karşılaşılan sorunlar ve yeni gelişmeler. Mikrobiyol Bul. 2014;48(4).
  • Faridi R, Zahra A, Khan K, Idrees M. Oncogenic potential of human papillomavirus (HPV) and its relation with cervical cancer. Virol J. 2011;8:1-8.
  • Abreu ALP, Souza RP, Gimenes F, Consolaro MEL. A review of methods for detect human Papillomavirus infection. Virol J. 2012;9(1):1-9.
  • Zur Hausen H. Molecular pathogenesis of cancer of the cervix and its causation by specific human papillomavirus types. Curr Top Microbiol Immunol. 1994;186:131-156.
  • Salazar KL, Duhon DJ, Olsen R, Thrall M. A review of the FDA-approved molecular testing platforms for human papillomavirus. J Am Soc Cytopathol. 2019;8(5):284-292.
  • Nih.gov [homepage on the Internet]. Ankara: The Papillomavirus Episteme. Cited [2022 August 19]. Available from: https://pave.niaid.nih.gov/locus_viewer?seq_id=HPV16REF.
  • Lenhoff A. Five FDA-approved HPV assays. MLO Med Lab Obs. 2012;44(7):14,16,18.
  • Shen-Gunther J, Yu X. HPV molecular assays: Defining analytical and clinical performance characteristics for cervical cytology specimens. Gynecol Oncol. 2011;123(2):263-271.
  • Hubbard RA. Human papillomavirus testing methods. Arch Pathol Lab Med. 2003;127(8):940-945.
  • Villa LL, Denny L. Methods for detection of HPV infection and its clinical utility. Int J Gynecol Obstet. 2006;94(SUPPL. 1).
  • Wei ZT, Chen HL, Wang CF, et al. Depiction of Vaginal Microbiota in Women With High-Risk Human Papillomavirus Infection. Front Public Heal. 2021;8(January):1-10.
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975;98(3):503-517.
  • Hwang SJ, Shroyer KR. Biomarkers of cervical dysplasia and carcinoma. J Oncol. 2012;2012.
  • Meyer T, Arndt R, Stockfleth E, et al. Strategy for typing human papillomaviruses by RFLP analysis of PCR products and subsequent hybridization with a generic probe. Biotechniques. 1995;19(4):632-639.
  • Takács T, Jeney C, Kovács L, et al. Molecular beacon-based real-time PCR method for detection of 15 high-risk and 5 low-risk HPV types. J Virol Methods. 2008;149(1):153-162.
  • Gibson UEM, Heid CA, Williams PM. A novel method for real time quantitative RT-PCR. Genome Res. 1996;6(10):995-1001.
  • Ilhan ZE, Łaniewski P, Thomas N, et al. Deciphering the complex interplay between microbiota, HPV, inflammation, and cancer through cervicovaginal metabolic profiling. EBioMedicine. 2019;44:675-690.
  • Magaji YG, Kolo I, Baba J, Suleiman KO. An overview of the general characteristics, pathogenicity, transmission, and diagnosis of human papillomavirus (HPV). 2022;1(1):27-39.
  • Castle PE, Lorincz AT, Mielzynska-Lohnas I, et al. Results of human papillomavirus DNA testing with the Hybrid Capture 2 assay are reproducible. J Clin Microbiol. 2002;40(3):1088-1090.
  • Castle PE, Wheeler CM, Solomon D, Schiffman M, Peyton CL. Interlaboratory reliability of hybrid capture 2. Am J Clin Pathol. 2004;122(2):238-245.
  • Kurian EM, Caporelli ML, Baker S, et al. Cervista HR and HPV 16/18 assays vs hybrid capture 2 assay: Outcome comparison in women with negative cervical cytology. Am J Clin Pathol. 2011;136(5):808-816.
  • Min KJ, So KA, Lee J, et al. Comparison of the Seeplex HPV4A ACE and the Cervista HPV assays for the detection of HPV in hybrid capture 2 positive media. J Gynecol Oncol. 2012;23(1):5-10.
  • Day SP, Hudson A, Mast A, et al. Analytical performance of the Investigational Use Only CervistaTM HPV HR test as determined by a multi-center study. J Clin Virol. 2009;45(SUPPL. 1):S63-S72.
  • Einstein MH, Martens MG, Garcia FAR, et al. Clinical validation of the Cervista® HPV HR and 16/18 genotyping tests for use in women with ASC-US cytology. Gynecol Oncol. 2010;118(2):116-122.
  • Guo M, Khanna A, Dawlett M, et al. Efficacy of reflex HPV16/18 genotyping in predicting CIN3/VAIN3 in women with HPV+/Pap– results. J Am Soc Cytopathol. 2016;5(1):31-36.
  • Einstein MH, Garcia FAR, Mitchell AL, Day SP. Age-stratified performance of the cervista HPV 16/18 genotyping test in women with ASC-US cytology. Cancer Epidemiol Biomarkers Prev. 2011;20(6):1185-1189.
  • Bartholomew DA, Luff RD, Quigley NB, Curtis M, Olson MC. Analytical performance of Cervista ® HPV 16/18 genotyping test for cervical cytology samples. J Clin Virol. 2011;51(1):38-43.
  • Guo M, Khanna A, Dhillon J, et al. Cervista HPV assays for fine-needle aspiration specimens are a valid option for human papillomavirus testing in patients with oropharyngeal carcinoma. Cancer Cytopathol. 2014;122(2):96-103.
  • Genta MLND, Martins TR, Lopez RVM, et al. Multiple HPV genotype infection impact on invasive cervical cancer presentation and survival. PLoS One. 2017;12(8):1-10.
  • Fda.gov [homepage on the Internet]. Ankara: cobas HPV Test South Branchburg: Roche Molecular Systems. Cited [2022 August 4]. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf10/p100020s017c.pdf.
  • Chao X, Sun T, Wang S, et al. Research of the potential biomarkers in vaginal microbiome for persistent high-risk human papillomavirus infection. Ann Transl Med. 2020;8(4):100-100.
  • Rao A, Young S, Erlich H, et al. Development and characterization of the cobas human papillomavirus test. J Clin Microbiol. 2013;51(5):1478-1484.
  • Motevaseli E, Azam R, Akrami SM, et al. The Effect of Lactobacillus crispatus and Lactobacillus rhamnosus Culture Supernatants on Expression of Autophagy Genes and HPV E6 and E7 Oncogenes in The HeLa Cell Line. Cell J. 2016;17(4):601-607.
  • Komatsu A, Igimi S, Kawana K. Optimization of human papillomavirus (HPV) type 16 E7-expressing lactobacillus-based vaccine for induction of mucosal E7-specific IFNγ-producing cells. Vaccine. 2018;36(24):3423-3426.
  • Hesselink AT, Berkhof J, Van Der Salm ML, et al. Clinical validation of the HPV-Risk assay, a novel real-time PCR assay for detection of high-risk human papillomavirus DNA by targeting the E7 region. J Clin Microbiol. 2014;52(3):890-896.
  • Stoler MH, Wright TC, Sharma A, et al. High-risk human papillomavirus testing in women with ASC-US cytology: Results from the athena HPV study. Am J Clin Pathol. 2011;135(3):468-475.
  • Fda.gov [homepage on the Internet]. Ankara. Aptima HPV Assay (Genprobe). Cited [2022 August 3]. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf10/P100042c.pdf.
  • Borgogna JC, Shardell MD, Santori EK, et al. The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis. BJOG. 2020;127(2):182-192.
  • Alemany L, Saunier M, Alvarado I, Quirós B, J S, Shin H. HPV DNA prevalence and type distribution in anal carcinomas worldwide. Int J Cancer. 2015;136(1):1-23.
  • Ratnam S, Coutlee F, Fontaine D, et al. Aptima HPV E6/E7 mRNA test is as sensitive as hybrid capture 2 assay but more specific at detecting cervical precancer and cancer. J Clin Microbiol. 2011;49(2):557-564.
  • Castle PE, Eaton B, Reid J, Getman D, Dockter J. Comparison of human papillomavirus detection by Aptima HPV and cobas HPV tests in a population of women referred for colposcopy following detection of atypical squamous cells of undetermined significance by Pap cytology. J Clin Microbiol. 2015;53(4):1277-1281.
  • Preisler S, Rebolj M, Ejegod DM, Lynge E, Rygaard C, Bonde J. Cross-reactivity profiles of hybrid capture II, cobas, and APTIMA human papillomavirus assays: Split-sample study. BMC Cancer. 2016;16(1):1-13.
  • Fda.gov [homepage on the Internet]. Ankara. BD OnclarityTM HPV Assay. Cited [2022 August 5]. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf16/P160037C.pdf.
  • Ejegod DM, Junge J, Franzmann M, et al. Clinical and analytical performance of the BD OnclarityTM HPV assay for detection of CIN2+ lesions on SurePath samples. Papillomavirus Res. 2016;2:31-37.
  • Bottari F, Sideri M, Gulmini C, et al. Comparison of onclarity Human Papillomavirus (HPV) assay with hybrid capture II HPV DNA assay for detection of cervical intraepithelial neoplasia grade 2 and 3 lesions. J Clin Microbiol. 2015;53(7):2109-2114.
  • Fda.gov [homepage on the Internet]. Ankara. Hybrid Capture 2. HC2 High-Risk HPV DNA Test. Cited [2022 August 5]. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf/P890064S009c.pdf.
  • Fda.gov [homepage on the Internet]. Ankara. Cervista HPV 16/18. Cited [2022 August 5]. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf8/p080015c.pdf.
  • Fda.gov [homepage on the Internet]. Ankara. Cervista HPV HR. Cited [2022 August 5]. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf8/p080014c.pdf.

SERVİKS KANSERİNE NEDEN OLAN HUMAN PAPİLLOMAVİRÜS (HPV) ENFEKSİYONLARININ TANIMLANMASI İÇİN KULLANILAN FDA ONAYLI MOLEKÜLER TESTLER

Year 2023, Volume: 45 Issue: 1, 1 - 11, 31.03.2023

Abdulhamit Çalı Rukiye Aslan Cem Çelik Ahmet Alim

https://doi.org/10.7197/cmj.1187503

Abstract

Keywords

Rahim ağzı kanseri Human papillomavirüs HPV Moleküler tanı

References

  • 1Ursu RG, Damian C, Porumb-Andrese E, et al. Merkel Cell Polyoma Virus and Cutaneous Human Papillomavirus Types in Skin Cancers: Optimal Detection Assays, Pathogenic Mechanisms, and Therapeutic Vaccination. Pathogens. 2022;11(4).
  • Ryan KJ. (Us AD, Başustaoğlu A, eds.). Sherris Tibbi̇ Mi̇krobi̇yoloji̇. Yedinci Baskı. Ankara. Hipokrat Yayınevi; 2019.
  • Taberna M, Mena M, Pavón MA, et al. Human papillomavirus-related oropharyngeal cancer. Ann Oncol. 2017;28(10):2386-2398.
  • Şahiner F. Genital insan papillomavirus enfeksiyonlarının moleküler tanısında karşılaşılan sorunlar ve yeni gelişmeler. Mikrobiyol Bul. 2014;48(4).
  • Faridi R, Zahra A, Khan K, Idrees M. Oncogenic potential of human papillomavirus (HPV) and its relation with cervical cancer. Virol J. 2011;8:1-8.
  • Abreu ALP, Souza RP, Gimenes F, Consolaro MEL. A review of methods for detect human Papillomavirus infection. Virol J. 2012;9(1):1-9.
  • Zur Hausen H. Molecular pathogenesis of cancer of the cervix and its causation by specific human papillomavirus types. Curr Top Microbiol Immunol. 1994;186:131-156.
  • Salazar KL, Duhon DJ, Olsen R, Thrall M. A review of the FDA-approved molecular testing platforms for human papillomavirus. J Am Soc Cytopathol. 2019;8(5):284-292.
  • Nih.gov [homepage on the Internet]. Ankara: The Papillomavirus Episteme. Cited [2022 August 19]. Available from: https://pave.niaid.nih.gov/locus_viewer?seq_id=HPV16REF.
  • Lenhoff A. Five FDA-approved HPV assays. MLO Med Lab Obs. 2012;44(7):14,16,18.
  • Shen-Gunther J, Yu X. HPV molecular assays: Defining analytical and clinical performance characteristics for cervical cytology specimens. Gynecol Oncol. 2011;123(2):263-271.
  • Hubbard RA. Human papillomavirus testing methods. Arch Pathol Lab Med. 2003;127(8):940-945.
  • Villa LL, Denny L. Methods for detection of HPV infection and its clinical utility. Int J Gynecol Obstet. 2006;94(SUPPL. 1).
  • Wei ZT, Chen HL, Wang CF, et al. Depiction of Vaginal Microbiota in Women With High-Risk Human Papillomavirus Infection. Front Public Heal. 2021;8(January):1-10.
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975;98(3):503-517.
  • Hwang SJ, Shroyer KR. Biomarkers of cervical dysplasia and carcinoma. J Oncol. 2012;2012.
  • Meyer T, Arndt R, Stockfleth E, et al. Strategy for typing human papillomaviruses by RFLP analysis of PCR products and subsequent hybridization with a generic probe. Biotechniques. 1995;19(4):632-639.
  • Takács T, Jeney C, Kovács L, et al. Molecular beacon-based real-time PCR method for detection of 15 high-risk and 5 low-risk HPV types. J Virol Methods. 2008;149(1):153-162.
  • Gibson UEM, Heid CA, Williams PM. A novel method for real time quantitative RT-PCR. Genome Res. 1996;6(10):995-1001.
  • Ilhan ZE, Łaniewski P, Thomas N, et al. Deciphering the complex interplay between microbiota, HPV, inflammation, and cancer through cervicovaginal metabolic profiling. EBioMedicine. 2019;44:675-690.
  • Magaji YG, Kolo I, Baba J, Suleiman KO. An overview of the general characteristics, pathogenicity, transmission, and diagnosis of human papillomavirus (HPV). 2022;1(1):27-39.
  • Castle PE, Lorincz AT, Mielzynska-Lohnas I, et al. Results of human papillomavirus DNA testing with the Hybrid Capture 2 assay are reproducible. J Clin Microbiol. 2002;40(3):1088-1090.
  • Castle PE, Wheeler CM, Solomon D, Schiffman M, Peyton CL. Interlaboratory reliability of hybrid capture 2. Am J Clin Pathol. 2004;122(2):238-245.
  • Kurian EM, Caporelli ML, Baker S, et al. Cervista HR and HPV 16/18 assays vs hybrid capture 2 assay: Outcome comparison in women with negative cervical cytology. Am J Clin Pathol. 2011;136(5):808-816.
  • Min KJ, So KA, Lee J, et al. Comparison of the Seeplex HPV4A ACE and the Cervista HPV assays for the detection of HPV in hybrid capture 2 positive media. J Gynecol Oncol. 2012;23(1):5-10.
  • Day SP, Hudson A, Mast A, et al. Analytical performance of the Investigational Use Only CervistaTM HPV HR test as determined by a multi-center study. J Clin Virol. 2009;45(SUPPL. 1):S63-S72.
  • Einstein MH, Martens MG, Garcia FAR, et al. Clinical validation of the Cervista® HPV HR and 16/18 genotyping tests for use in women with ASC-US cytology. Gynecol Oncol. 2010;118(2):116-122.
  • Guo M, Khanna A, Dawlett M, et al. Efficacy of reflex HPV16/18 genotyping in predicting CIN3/VAIN3 in women with HPV+/Pap– results. J Am Soc Cytopathol. 2016;5(1):31-36.
  • Einstein MH, Garcia FAR, Mitchell AL, Day SP. Age-stratified performance of the cervista HPV 16/18 genotyping test in women with ASC-US cytology. Cancer Epidemiol Biomarkers Prev. 2011;20(6):1185-1189.
  • Bartholomew DA, Luff RD, Quigley NB, Curtis M, Olson MC. Analytical performance of Cervista ® HPV 16/18 genotyping test for cervical cytology samples. J Clin Virol. 2011;51(1):38-43.
  • Guo M, Khanna A, Dhillon J, et al. Cervista HPV assays for fine-needle aspiration specimens are a valid option for human papillomavirus testing in patients with oropharyngeal carcinoma. Cancer Cytopathol. 2014;122(2):96-103.
  • Genta MLND, Martins TR, Lopez RVM, et al. Multiple HPV genotype infection impact on invasive cervical cancer presentation and survival. PLoS One. 2017;12(8):1-10.
  • Fda.gov [homepage on the Internet]. Ankara: cobas HPV Test South Branchburg: Roche Molecular Systems. Cited [2022 August 4]. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf10/p100020s017c.pdf.
  • Chao X, Sun T, Wang S, et al. Research of the potential biomarkers in vaginal microbiome for persistent high-risk human papillomavirus infection. Ann Transl Med. 2020;8(4):100-100.
  • Rao A, Young S, Erlich H, et al. Development and characterization of the cobas human papillomavirus test. J Clin Microbiol. 2013;51(5):1478-1484.
  • Motevaseli E, Azam R, Akrami SM, et al. The Effect of Lactobacillus crispatus and Lactobacillus rhamnosus Culture Supernatants on Expression of Autophagy Genes and HPV E6 and E7 Oncogenes in The HeLa Cell Line. Cell J. 2016;17(4):601-607.
  • Komatsu A, Igimi S, Kawana K. Optimization of human papillomavirus (HPV) type 16 E7-expressing lactobacillus-based vaccine for induction of mucosal E7-specific IFNγ-producing cells. Vaccine. 2018;36(24):3423-3426.
  • Hesselink AT, Berkhof J, Van Der Salm ML, et al. Clinical validation of the HPV-Risk assay, a novel real-time PCR assay for detection of high-risk human papillomavirus DNA by targeting the E7 region. J Clin Microbiol. 2014;52(3):890-896.
  • Stoler MH, Wright TC, Sharma A, et al. High-risk human papillomavirus testing in women with ASC-US cytology: Results from the athena HPV study. Am J Clin Pathol. 2011;135(3):468-475.
  • Fda.gov [homepage on the Internet]. Ankara. Aptima HPV Assay (Genprobe). Cited [2022 August 3]. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf10/P100042c.pdf.
  • Borgogna JC, Shardell MD, Santori EK, et al. The vaginal metabolome and microbiota of cervical HPV-positive and HPV-negative women: a cross-sectional analysis. BJOG. 2020;127(2):182-192.
  • Alemany L, Saunier M, Alvarado I, Quirós B, J S, Shin H. HPV DNA prevalence and type distribution in anal carcinomas worldwide. Int J Cancer. 2015;136(1):1-23.
  • Ratnam S, Coutlee F, Fontaine D, et al. Aptima HPV E6/E7 mRNA test is as sensitive as hybrid capture 2 assay but more specific at detecting cervical precancer and cancer. J Clin Microbiol. 2011;49(2):557-564.
  • Castle PE, Eaton B, Reid J, Getman D, Dockter J. Comparison of human papillomavirus detection by Aptima HPV and cobas HPV tests in a population of women referred for colposcopy following detection of atypical squamous cells of undetermined significance by Pap cytology. J Clin Microbiol. 2015;53(4):1277-1281.
  • Preisler S, Rebolj M, Ejegod DM, Lynge E, Rygaard C, Bonde J. Cross-reactivity profiles of hybrid capture II, cobas, and APTIMA human papillomavirus assays: Split-sample study. BMC Cancer. 2016;16(1):1-13.
  • Fda.gov [homepage on the Internet]. Ankara. BD OnclarityTM HPV Assay. Cited [2022 August 5]. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf16/P160037C.pdf.
  • Ejegod DM, Junge J, Franzmann M, et al. Clinical and analytical performance of the BD OnclarityTM HPV assay for detection of CIN2+ lesions on SurePath samples. Papillomavirus Res. 2016;2:31-37.
  • Bottari F, Sideri M, Gulmini C, et al. Comparison of onclarity Human Papillomavirus (HPV) assay with hybrid capture II HPV DNA assay for detection of cervical intraepithelial neoplasia grade 2 and 3 lesions. J Clin Microbiol. 2015;53(7):2109-2114.
  • Fda.gov [homepage on the Internet]. Ankara. Hybrid Capture 2. HC2 High-Risk HPV DNA Test. Cited [2022 August 5]. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf/P890064S009c.pdf.
  • Fda.gov [homepage on the Internet]. Ankara. Cervista HPV 16/18. Cited [2022 August 5]. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf8/p080015c.pdf.
  • Fda.gov [homepage on the Internet]. Ankara. Cervista HPV HR. Cited [2022 August 5]. Available from: https://www.accessdata.fda.gov/cdrh_docs/pdf8/p080014c.pdf.
There are 51 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Reviews
Authors

Abdulhamit Çalı 0000-0001-6423-9609

Rukiye Aslan 0000-0001-5843-626X

Cem Çelik 0000-0002-7141-5874

Ahmet Alim 0000-0001-9577-5965

Publication Date March 31, 2023
Acceptance Date March 26, 2023
Published in Issue Year 2023Volume: 45 Issue: 1

Cite

AMA Çalı A, Aslan R, Çelik C, Alim A. FDA-APPROVED MOLECULAR TESTS USED TO DEFINE HUMAN PAPILLOMAVIRUS (HPV) INFECTIONS WHICH CAUSE CERVIX CANCER. CMJ. March 2023;45(1):1-11. doi:10.7197/cmj.1187503
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