Archives of Virology

, Volume 128, Issue 1–2, pp 123–133 | Cite as

Definition of human papillomavirus type 16 DNA levels in low and high grade cervical lesions by a simple polymerase chain reaction technique

  • G. Terry
  • L. Ho
  • D. Jenkins
  • M. Hills
  • A. Singer
  • B. Mansell
  • E. Beverley
Original Papers


Human papillomavirus type 16 (HPV 16) is associated with a high proportion of cervical cancers and pre-cancers but has also been reported by some workers to be widely distributed in the normal population. Using a semi-quantitative polymerase chain reaction technique (PCR) operated with carefully regulated sensitivity we have established two distinct levels of HPV 16 DNA which distinguish between high and low grade cervical lesions. The potential use of such an approach in the understanding and management of HPV related cervical disease is discussed.


Polymerase Chain Reaction Infectious Disease Cervical Cancer Normal Population Cervical Lesion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Bauer HM, Ting Y, Greer CE, Chambers JC, Tashiro C, Chimera J, Reingold A, Manos MM (1991) Genital human papillomavirus infection in female university students as determined by a PCR-based method. JAMA 265: 472–477Google Scholar
  2. 2.
    Buckley CH, Butler EB, Fox H (1982) Cervical intraepithelial neoplasia. J Clin Pathol 35: 1–13Google Scholar
  3. 3.
    Campion MJ, McCance DJ, Cuzick J, Singer A (1986) Progressive potential of mild cervical atypia: a colposcopic, cytological and virological study. Lancet ii: 237–240Google Scholar
  4. 4.
    Collins JE, Jenkins D, McCance DJ (1988) Detection of human papillomavirus DNA sequences by in situ DNA-DNA hybridisation in cervical intraepithelial neoplasia and invasive carcinoma: a retrospective study. J Clin Pathol 41: 289–295Google Scholar
  5. 5.
    Cornelissen MTE, Smits HL, Briet MA, van den Tweel JG, Struyk APHB, van der Noordaa J, ter Schegget J (1990) Uniformity of the splicing pattern of the E6/E7 transcripts in human papillomavirus type 16-transformed human fibroblasts, human cervical premalignant lesions and carcinomas. J Gen Virol 71: 1243–1246Google Scholar
  6. 6.
    Crum CP, Mitao M, Levine RU, Silverstein S (1985) Cervical papillomaviruses segregate within morphologically distinct precancerous lesions. J Virol 54: 675–681Google Scholar
  7. 7.
    Cullen AP, Reid R, Campion M, Lorincz AT (1991) Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasia. J Virol 65: 606–612Google Scholar
  8. 8.
    Cuzick J, Singer A, de Stavola BL, Chomet J (1990) Case-control study of risk factors for cervical intraepithelial neoplasia in young women. Eur J Cancer 26: 684–690Google Scholar
  9. 9.
    Cuzick J, Terry G, Ho L, Hollingworth T, Anderson M (1992) Human papillomavirus type 16 DNA in cervical smears as a predictor of high grade cervical intraepithelial neoplasia. Lancet 339: 959–960Google Scholar
  10. 10.
    Di Luca D, Pilotti S, Stefanon B, Rotola A, Monini P, Tognon M, de Palo G, Rilke F, Cassai E (1986) Human papillomavirus type 16 DNA in genital tumours: a pathological and molecular analysis. J Gen Virol 67: 583–589Google Scholar
  11. 11.
    Durst M, Kleinheinz A, Hotz M, Gissmann L (1985) The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumour. J Gen Virol 66: 1515–1522Google Scholar
  12. 12.
    Durst M, Dzarlieva-Petrusevska RT, Boukamp P, Fusenig NE, Gissmann L (1987) Molecular and cytogenetic analysis of immortalized human primary keratinocytes obtained after transfection with human papillomavirus type 16 DNA. Oncogene 1: 251–256Google Scholar
  13. 13.
    El Awady MF, Kaplan JB, O'Brien SJ, Burk RD (1987) Molecular analysis of integrated human papillomavirus 16 sequences in the cervical cancer cell line SiHa. Virology 159: 389–398Google Scholar
  14. 14.
    Ferenczy A, Winkler B (1987) Anatomy and histology of the cervix. In: Kurman R (ed) Blaustein's pathology of the female genital tract, 3rd edn. Springer, New YorkGoogle Scholar
  15. 15.
    Fuchs PG, Girardi F, Pfister H (1988) Human papillomavirus DNA in normal, metaplastic, preneoplastic and neoplastic epithelia of the cervix uteri. Int J Cancer 41: 41–45Google Scholar
  16. 16.
    Fukushima M, Yamakawa Y, Shimano S, Hashimoto M, Sawada Y, Fujinaga K (1990) The physical state of human papillomavirus 16 DNA in cervical carcinoma and cervical intraepithelial neoplasia. Cancer 66: 2155–2161Google Scholar
  17. 17.
    Gilliland G, Perrin S, Blanchard D, Bunn HF (1990) Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction. Proc Natl Acad Sci 87: 2725–2729Google Scholar
  18. 18.
    Hawley-Nelson P, Vousden KH, Hubbert NL, Lowy DR, Schiller JT (1989) HPV 16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. EMBO J 8: 3905–3910Google Scholar
  19. 19.
    Heger S, Gissmann L (1990) Attempts to identify integration of HPV-DNA in CIN-lesions and condylomata acuminata. Papillomavirus Workshop 1990, Heidelberg, p 187Google Scholar
  20. 20.
    Ho-Terry L, Terry GM, Londesborough P (1990) Diagnosis of foetal rubella virus infection by polymerase chain reaction. J Gen Virol 71: 1607–1611Google Scholar
  21. 21.
    Kaur P, McDougall JK, Cone R (1989) Immortalization of primary human epithelial cells by cloned cervical carcinoma DNA containing human papillomavirus type 16 E6/E7 open reading frames. J Gen Virol 70: 1261–1266Google Scholar
  22. 22.
    Lorincz AT, Lancaster WD, Temple GF (1986) Cloning and characterisation of the DNA of a new human papillomavirus from a woman with dysplasia of the uterine cervix. J Virol 58: 225–228Google Scholar
  23. 23.
    Maniatis T, Fritsch EF, Sambrook J (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, New YorkGoogle Scholar
  24. 24.
    Manos M, Lee K, Greer C, Waldman J, Kiviat N, Holmes K, Wheeler C (1990) Looking for human papillomavirus type 16 by PCR. Lancet 335: 734Google Scholar
  25. 25.
    McCance DJ, Campion MJ, Clarkson PK, Chester PM, Jenkins D, Singer A (1985) Prevalence of human papillomavirus type 16 DNA sequences in cervical intra-epithelial neoplasia and invasive carcinoma of the cervix. Br J Obstet Gyn 92: 1101–1105Google Scholar
  26. 26.
    McIndoe WA, McLean MR, Jones RW, Mullins PR (1984) The invasive potential of carcinoma in situ of the cervix. J Am College Obstet Gyn 64: 451–458Google Scholar
  27. 27.
    Munger K, Phelps WC, Bubb V, Howley PM, Schlegel R (1989) The E6 and E7 genes of the human papillomavirus type 16 together are necessary and sufficient for transformation of primary human keratinocytes. J Virol 63: 4417–4421Google Scholar
  28. 28.
    Nuovo GJ, Darfler MM, Impraim CC, Bromley SE (1991) Occurrence of multiple types of human papillomavirus in genital tract lesions. Am J Pathol 138: 53–58Google Scholar
  29. 29.
    Richart RM (1990) A modified terminology for cervical intraepithelial neoplasia. Obstet Gyn 75: 131–133Google Scholar
  30. 30.
    Romanczuk H, Villa LL, Schlegel R, Howley PM (1991) The viral transcriptional regulatory region upstream of the E6 and E7 genes is a major determinant of the differential immortalization activities of human papillomavirus types 16 and 18. J Virol 65: 2739–2744Google Scholar
  31. 31.
    Schneider A, Oltersdorf T, Schneider V, Gissman L (1987) Distribution pattern of human papilloma virus 16 genome in cervical neoplasia by molecular in situ hybridisation of tissue sections. Int J Cancer 39: 717–721Google Scholar
  32. 32.
    Schneider-Maunoury S, Croissant O, Orth G (1987) Integration of human papillomavirus type 16 DNA sequences: a possible early event in the progression of genital tumours. J Virol 61: 3295–3298Google Scholar
  33. 33.
    Seedorf K, Krammer G, Durst M, Suhai S, Rowekamp WG (1985) Human papillomavirus type 16 DNA sequence. Virology 145: 181–185Google Scholar
  34. 34.
    Shirasawa H, Tomita Y, Kubota K, Kaiae T, Sekiya S, Takamizawa H, Simizu B (1986) Detection of human papillomavirus type 16 DNA and evidence for integration into the cell DNA in cervical dysplasia. J Gen Virol 67: 2011–2015Google Scholar
  35. 35.
    Smotkin D, Prokoph H, Wettstein FO (1989) Oncogenic and nononcogenic human genital papillomaviruses generate the E7 mRNA by different mechanisms. J Virol 63: 1441–1447Google Scholar
  36. 36.
    Van den Brule AJC, Claas ECJ, du Maine M, Melchers WJG, Helmerhorst T, Quint WGV, Lindeman J, Meijer CJLM, Walboomers JMM (1989) The use of anti-contamination primers in the polymerase chain reaction for the detection of human papilloma virus genotypes in cervical scrapes and biopsies. J Med Virol 29: 20–27Google Scholar
  37. 37.
    Van den Brule AJC, Snijders PJF, Gordijn RLJ, Bleker OP, Meijer CJLM, Walboomers JMM (1990) General primer-mediated polymerase chain reaction permits the detection of sequenced and still unsequenced human papillomavirus genotypes in cervical scrapes and carcinomas. Int J Cancer 45: 644–649Google Scholar
  38. 38.
    Van den Brule AJC, Walboomers JMM, Du Maine M, Kenemans P, Meijer CJLM (1991) Difference in prevalence of human papillomavirus genotypes in cytomorphologically normal cervical smears is associated with a history of cervical intraepithelial neoplasia. Int J Cancer 48: 404–408Google Scholar
  39. 39.
    Young LS, Bevan IS, Johnson MA, Blomfield PI, Bromidge T, Maitland NJ, Woodman BCJ (1989) The polymerase chain reaction: a new epidemiological tool for investigating cervical human papillomavirus infection. Br Med J 298: 14–18Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • G. Terry
    • 1
    • 2
  • L. Ho
    • 1
    • 2
  • D. Jenkins
    • 3
  • M. Hills
    • 3
  • A. Singer
    • 4
  • B. Mansell
    • 4
  • E. Beverley
    • 4
  1. 1.Department of Chemical PathologyUniversity CollegeLondon
  2. 2.Department of Medical MicrobiologyUniversity CollegeLondon
  3. 3.Department of HistopathologyWhittington HospitalLondon
  4. 4.Department of GynaecologyRoyal Northern HospitalLondonUK

Personalised recommendations