CC BY-NC-ND 4.0 · J Lab Physicians 2022; 14(03): 336-342
DOI: 10.1055/s-0042-1748919
Original Article

Evaluation of HPV E6/E7 mRNA Detection in Clinically Suspected Cases of Cervical Cancer with Abnormal Cytology: Time to Upgrade the Screening Protocols

Bhawna Sharma
1   Department of Microbiology, Government Medical College, Amritsar, Punjab, India
Vikas Lakhanpal
2   Department of Internal Medicine, Government Medical College, Amritsar, Punjab, India
Kanwardeep Singh
1   Department of Microbiology, Government Medical College, Amritsar, Punjab, India
Loveena Oberoi
1   Department of Microbiology, Government Medical College, Amritsar, Punjab, India
Preet Kamal Bedi
3   Department of Obstetrics and Gynaecology, Government Medical College, Amritsar, Punjab, India
Pushpa Devi
1   Department of Microbiology, Government Medical College, Amritsar, Punjab, India
› Author Affiliations
Funding None.


Background Human papillomavirus (HPV) E6/E7 mRNA tests determine the oncogenic activity of the virus and represent a good clinical biomarker for predicting the risk of cervical cancer. So, the present study was conducted to know the role of HPV E6/E7 mRNA as a predictive biomarker for cervical carcinoma.

Methodology The present study was conducted on 55 clinical samples of cervical scrapings and biopsy from the clinically suspected cases (based on signs and symptoms) of cervical cancer having abnormal PAP smear. The samples were processed in three steps—(1) HPV DNA detection, (2) HPV E6/E7 mRNA detection, and (3) histopathological analysis.

Results Out of a total of 55 patients, 16 (29.09%) were positive for both HPV E6/E7 mRNA and HPV DNA and six were positive for only HPV DNA. So, a total of 22 (40%) patients were positive for HPV DNA. Out of these 22 samples, 10 (45.5%) were of HPV-16, six (27.3%) were of HPV-18, four (18.2%) were of HPV-31, and two (9.1%) were of HPV-45. Out of total 16 patients positive for HPV E6/E7 mRNA, 10 (62.5%) were of genotype 16 and six (37.5%) were of genotype 18. The patients who were found positive for HPV 31 and 45 genotypes did not have E6/E7 mRNA expression. On colposcopic-guided biopsy, among these 16 samples, eight (50%) were diagnosed with invasive squamous cell carcinoma, six (37.5%) with cervical intraepithelial neoplasia grade 3 (CIN3), and two (12.5%) with CIN2. Out of those six patients in whom only HPV DNA was positive, five had normal biopsy findings and one had CIN1.

Conclusion The present study suggests that HPV E6/E7 mRNA detection could be more reliable than DNA testing for predicting the risk of progression of HPV-induced cervical lesions to cervical carcinoma and it can be used as a non-invasive tool for triage and patient follow-up.


Ethical clearance was taken from institute's ethical committee.

Supplementary Material

Publication History

Article published online:
04 July 2022

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  • References

  • 1 Ferlay J, Soerjomataram I, Ervik M. et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No.11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013
  • 2 Stanley M. HPV—immune response to infection and vaccination. Infect Agent Cancer 2010; 5: 19
  • 3 Muñoz N, Bosch FX, de Sanjosé S. et al; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348 (06) 518-527
  • 4 Herrero R, Hildesheim A, Bratti C. et al. Population-based study of human papillomavirus infection and cervical neoplasia in rural Costa Rica. J Natl Cancer Inst 2000; 92 (06) 464-474
  • 5 Abreu ALP, Souza RP, Gimenes F, Consolaro ME. A review of methods for detect human Papillomavirus infection. Virol J 2012; 9: 262
  • 6 Hwang SJ, Shroyer KR. Biomarkers of cervical dysplasia and carcinoma. J Oncol 2012; 2012: 507286
  • 7 zur Hausen H. Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst 2000; 92 (09) 690-698
  • 8 Scheurer ME, Tortolero-Luna G, Guillaud M. et al. Correlation of human papillomavirus type 16 and human papillomavirus type 18 e7 messenger RNA levels with degree of cervical dysplasia. Cancer Epidemiol Biomarkers Prev 2005; 14 (08) 1948-1952
  • 9 Coquillard G, Palao B, Patterson BK. Quantification of intracellular HPV E6/E7 mRNA expression increases the specificity and positive predictive value of cervical cancer screening compared to HPV DNA. Gynecol Oncol 2011; 120 (01) 89-93
  • 10 Sørbye SW, Arbyn M, Fismen S, Gutteberg TJ, Mortensen ES. HPV E6/E7 mRNA testing is more specific than cytology in post-colposcopy follow-up of women with negative cervical biopsy. PLoS One 2011; 6 (10) e26022
  • 11 Kraus I, Molden T, Holm R. et al. Presence of E6 and E7 mRNA from human papillomavirus types 16, 18, 31, 33, and 45 in the majority of cervical carcinomas. J Clin Microbiol 2006; 44 (04) 1310-1317
  • 12 Molden T, Kraus I, Skomedal H, Nordstrøm T, Karlsen F. PreTect HPV-Proofer: real-time detection and typing of E6/E7 mRNA from carcinogenic human papillomaviruses. J Virol Methods 2007; 142 (1-2): 204-212
  • 13 Zerat L. La nouvelle terminologie de Bethesda: quellschangements? Rev Prat Gynecol Obstet. Numero Special 2002: 3-10
  • 14 Solomon D, Davey D, Kurman R. et al; Forum Group Members; Bethesda 2001 Workshop. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA 2002; 287 (16) 2114-2119
  • 15 Buckley CH, Butler EB, Fox H. Cervical intraepithelial neoplasia. J Clin Pathol 1982; 35 (01) 1-13
  • 16 Kaur H, Kaur S, Goyal L, Kaur P. Prevalence of carcinoma cervix in rural Punjab and need to create awareness regarding cervical cancer. Indian J Public Health Res Develop 2013; 4 (03) 111
  • 17 Senapati R, Nayak B, Kar SK, Dwibedi B. HPV genotypes distribution in Indian women with and without cervical carcinoma: implication for HPV vaccination program in Odisha, Eastern India. BMC Infect Dis 2017; 17 (01) 30
  • 18 Bzhalava D, Eklund C, Dillner J. International standardization and classification of human papillomavirus types. Virology 2015; 476: 341-344
  • 19 Origoni M, Cristoforoni P, Carminati G. et al. E6/E7 mRNA testing for human papilloma virus-induced high-grade cervical intraepithelial disease (CIN2/CIN3): a promising perspective. Ecancermedicalscience 2015; 9: 533
  • 20 Ho CM, Lee BH, Chang SF. et al. Type-specific human papillomavirus oncogene messenger RNA levels correlate with the severity of cervical neoplasia. Int J Cancer 2010; 127 (03) 622-632
  • 21 Molden T, Nygård JF, Kraus I. et al. Predicting CIN2+ when detecting HPV mRNA and DNA by PreTect HPV-proofer and consensus PCR: a 2-year follow-up of women with ASCUS or LSIL Pap smear. Int J Cancer 2005; 114 (06) 973-976
  • 22 Dabeski D, Duvlis S, Basheska N. et al. Comparison between HPV DNA testing and HPV E6/E7 MRNA testing in women with squamous cell abnormalities of the uterine cervix. Prilozi (Makedon Akad Nauk Umet Odd Med Nauki) 2019; 40 (01) 51-58 (Makedon Akad Nauk Umet Odd Med Nauki)
  • 23 Cuschieri K, Wentzensen N. Human papillomavirus mRNA and p16 detection as biomarkers for the improved diagnosis of cervical neoplasia. Cancer Epidemiol Biomarkers Prev 2008; 17 (10) 2536-2545
  • 24 Liu TY, Xie R, Luo L. et al. Diagnostic validity of human papillomavirus E6/E7 mRNA test in cervical cytological samples. J Virol Methods 2014; 196: 120-125
  • 25 Salimović-Bešić I, Tomić-Čiča A, Smailji A, Hukić M. Comparison of the detection of HPV-16, 18, 31, 33, and 45 by type-specific DNA- and E6/E7 mRNA-based assays of HPV DNA positive women with abnormal Pap smears. J Virol Methods 2013; 194 (1-2): 222-228
  • 26 Zhang S-K, Guo Z, Wang P. et al. The potential benefits of HPV E6/E7 mRNA test in cervical cancer screening in China. Front Oncol 2020; 10: 533253
  • 27 Duvlis S, Popovska-Jankovic K, Arsova ZS, Memeti S, Popeska Z, Plaseska-Karanfilska D. HPV E6/E7 mRNA versus HPV DNA biomarker in cervical cancer screening of a group of Macedonian women. J Med Virol 2015; 87 (09) 1578-1586
  • 28 Yao YL, Tian QF, Cheng B, Cheng YF, Ye J, Lu WG. Human papillomavirus (HPV) E6/E7 mRNA detection in cervical exfoliated cells: a potential triage for HPV-positive women. J Zhejiang Univ Sci B 2017; 18 (03) 256-262
  • 29 Hui C, Bai H, Liu J. et al. Accuracy of HPV E6/E7 mRNA examination using in situ hybridization in diagnosing cervical intraepithelial lesions. Diagn Pathol 2021; 16 (01) 13
  • 30 Sun J, Yue Y, Li R. et al. Detection of HPV E6/E7 mRNA in the diagnosis of cervical cancer and precancerous lesions after kidney transplantation. Am J Transl Res 2021; 13 (06) 7312-7317
  • 31 Wang HY, Kim H, Park KH. Diagnostic performance of the E6/E7 mRNA-based Optimygene HR-HPV RT-qDx assay for cervical cancer screening. Int J Infect Dis 2019; 78: 22-30
  • 32 Liu J, Yang T, Hu Y, Ye C. The value of HPV E6/E7 mRNA quantitative analysis in distinguishing high-grade cervical squamous intraepithelial lesions from low-grade cervical squamous intraepithelial lesions. J Virol Methods 2021; 289: 114014
  • 33 Aggarwal R, Gupta S, Nijhawan R. et al. Prevalence of high-risk human papillomavirus infections in women with benign cervical cytology: a hospital based study from North India. Indian J Cancer 2006; 43 (03) 110-116
  • 34 Asiaf A, Ahmad ST, Mohammad SO, Zargar MA. Review of the current knowledge on the epidemiology, pathogenesis, and prevention of human papillomavirus infection. Eur J Cancer Prev 2014; 23 (03) 206-224
  • 35 Rama CH, Roteli-Martins CM, Derchain SF. et al. [Prevalence of genital HPV infection among women screened for cervical cancer]. Rev Saude Publica 2008; 42 (01) 123-130
  • 36 Remschmidt C, Kaufmann AM, Hagemann I, Vartazarova E, Wichmann O, Deleré Y. Risk factors for cervical human papillomavirus infection and high-grade intraepithelial lesion in women aged 20 to 31 years in Germany. Int J Gynecol Cancer 2013; 23 (03) 519-526
  • 37 Available at: [cited Oct 3, 2021]