HPV Virus Scientific Facts - Research

Fuessel Haws AL, He Q, Rady PL, Zhang L, Grady J, Hughes TK, Stisser K, Konig R, Tyring SK. Department of Microbiology, University of Texas Medical Branch, Galveston, TX 77030, USA.

Based on epidemiological and research evidence, HPV has a causal role in cervical carcinogenesis. Several HPV detection methods exist to date; the most commonly used method for detection of genital HPVs consists of nested PCR using the MY09/11 and GP5(+)/6(+) primer sets (MY/GP(+)). Recently, the PGMY09/11 primer set, a modified version of the MY09/11 primer set, was introduced for single PCR and was found to detect a wider range of HPV types. The next logical step was taken and the efficacy of nested PCR using the PGMY09/11 and GP5(+)/6(+) primer sets (PGMY/GP(+)) to detect HPV in cervical samples was evaluated. In this comparative study, nested PCR using the novel PGMY/GP(+) primer set combination was found to be more type sensitive than the nested PCR with the MY/GP(+) primer sets, detecting a wider range of HPV types, low copy HPVs, and better characterizing samples infected with multiple strains of HPV. Standardization and use of the PGMY/GP(+) PCR system could aid physicians in providing more efficient HPV screening and better treatment for patients.

Publication Types:
• Evaluation Studies

Int J Gynecol Cancer. 2005 Jan-Feb;15(1):4-12.

Chemoprevention and vaccines: a review of the nonsurgical options for the treatment of cervical dysplasia.

Bell MC, Alvarez RD. The University of South Dakota School of Medicine, Vermillion, SD, USA.

Human papillomavirus (HPV)-related disease is a significant health problem in the United States and throughout the world, especially in developing countries. Standard treatment to date has been surgical excision, but we ask the question "For what other clinically evident, virally mediated disease is the standard of treatment surgery?" The authors performed a systematic literature review and selected articles most relevant to the topic. This article reviews prevention, chemoprevention, and vaccine trials for the prevention and treatment of HPV-related disease of the genital tract. Significant advances have been made in the last decade, and the future holds promise for effective nonsurgical options for the patients with cervical dysplasia and other HPV-associated diseases.

Clin Infect Dis. 2005 Feb 1;40(3):451-7. Epub 2005 Jan 7.

Determination of human papillomavirus (HPV) load and type in high-grade cervical lesions surgically resected from HIV-infected women during follow-up of HPV infection.

Lillo FB, Lodini S, Ferrari D, Stayton C, Taccagni G, Galli L, Lazzarin A, Uberti-Foppa C. Laboratory of Virology, Scientific Institute San Raffaele, Milan, Italy.

BACKGROUND: The role of human papillomavirus (HPV) load and the importance of multiple-strain HPV infections as biomarkers for the development of cervical disease were evaluated in human immunodeficiency virus (HIV)-positive women. METHODS: A total of 108 samples were analyzed, 64 of which were obtained from 16 HIV-positive women who underwent surgical resection of the cervical cone for treatment of a histologically confirmed high-grade cervical intraepithelial neoplasm (cases) and 44 of which were obtained from 22 HIV-positive women who had high-risk HPV but a negative colposcopy result (controls). Each patient underwent periodic examinations at 6-12-month intervals that included colposcopy, Papanicolaou testing, biopsy (if indicated), and cervical brushing for HPV testing. Viral typing was performed by reverse dot-blot hybridization and quantification of viral load by in-house real-time PCR and commercial assays. RESULTS: Analysis of the cervical-brush samples collected when high-grade squamous intraepithelial lesions were diagnosed revealed that all cases had HPV loads that were significantly higher than those of controls (P=.0004 and P=.0003, by PCR and the Hybrid Capture 2 index [Digene], respectively). Decreasing concentrations of HPV load were observed when comparing samples obtained before and after treatment (P<.0001). The number and type of HPV strains that were detected were not statistically different between cases and controls. CONCLUSIONS: The significantly higher HPV load detected in women with high-grade cervical dysplasia, as well as the dramatic decrease in the load after surgical removal of the lesion, suggest that HPV load is a possible prognostic marker of high-grade SIL.

Arkh Patol. 2004 Sep-Oct;66(5):35-9.

Traditional and new molecular methods for early detection of cervical cancer.

Dallenbach-Hellweg G, Trunk MJ, von Knebel Doeberitz M. Institute for Pathology, A2, 2, D-68159 Mannheim, Germany.

Disadvantages of the traditional Papanicolaou-method for the cytological detection of cervical carcinomas and their precursors can be overcome by the use of specific molecular markers for nuclear attypicality. High grade HR-HPV induced cervical dysplasia is initiated by deregulated expression of viral oncogenes in replicating epithelial stem cells. Here, the E6-E7 gene products gain control of cell cycle and mitotic activity first and induce multistep mutagenesis with severe genomic instability in successin. The detailed molecular analysis of these activities has allowed the development of biomarkers for dysplastic cervical cells. The marked over-expression of the cyclin dependent kinase inhibitor p16INK4a is regularly observed in HR-HPV induced malignant lesions and indicates an active expression of the viral oncogene E7 in dysplastic cells. Morphologically, these molecular deregulations are reflected mainly in an altered nuclear-cytoplasmic ratio, anisonucleosis, and hyperchromasia. With p16INK4a immunostaining--as reported in the literature--dysplastic and atypical cells can be easily detected even under low magnification and differentiated by higher magnification from occasional positive atrophic or metaplastic cells by their atypical nuclear structure. In questionable cases the additional use of proliferation markers could eliminate false interpretation. The results with these new molecular techniques can by further optimized by applying the ThinPrep-method for the preparation of the cytological slides to ensure overlying blood, mucus or inflammatory cells do not mask atypical cells. With these new methods we can expect to lower the rate of false-positive and false-negative cytology tests as experienced with the traditional Papanicolaou-method, of not eliminate them completely, gaining thereby great advantages for patients and for cost-efficiency.

Acta Cytol. 2004 Mar-Apr;48(2):273-7.

Double cervix with bilateral and synchronous HSIL associated with different high-risk HPV types. A case report.

Pinto KR, Lu DW, Rader JS, Davila RM. Department of Pathology and Immunology, Washington University Medical Center, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.

BACKGROUND: High grade squamous intraepithelial lesion (HSIL) of the cervix is well known to be associated with human papillomavirus (HPV) infection. HSIL and invasive carcinomas occurring synchronously in genital malformations, such as a double cervix, have been reported. It has been postulated that the field effect phenomenon of HPV infection is responsible for this synchronous infection. However, there is no information in the literature on the specific types of HPV causing the concomitant lesions in cases with a double cervix. CASE: A 33-year-old nulligravida with a double cervix and a single uterine corpus was diagnosed with bilateral HSIL on Papanicolaou-stained ThinPrep slides (Cytyc Corp., Boxborough, Massachusetts, U.S.A.). A bilateral loop electrosurgical excision procedure cone biopsy revealed HSIL involving both cervices. DNA extracted from the HSIL lesions was analyzed by a polymerase chain reaction-based assay for the presence of HPV. High-risk HPV type 33 was identified in the right cervix, while HPV type 35 was present in the left. CONCLUSION: Demonstration of high-risk HPV types bilaterally supported the etiologic role of HPV infection in the synchronous and bilateral occurrence of HSIL in this case of a double cervix. The HPV types were different in the right and left cervices.

Publication Types:
• Case Reports

Br J Cancer. 2004 Apr 5;90(7):1407-13.

Human papillomavirus oncogenic expression in the dysplastic portio; an investigation of biopsies from 190 cervical cones.

Kraus I, Molden T, Erno LE, Skomedal H, Karlsen F, Hagmar B. Institute of Pathology, The National University Hospital, 0027 Oslo, Norway.

In this study, we investigated the presence of E6/E7 transcripts of seven common high-risk human papillomavirus (HPV) types in 190 cervical biopsies. The RNA-based real-time nucleic acid sequence-based amplification assay (NASBA) and type-specific PCR, both detecting HPV 16, 18, 31, 33, 45, 52, and 58, as well as consensus PCR, were performed on all 190 biopsies. High accordance between type-specific and consensus PCR confirms that the HPV types included in this study are the most common types present in cervical dysplasia. Furthermore, we see a clear increase in the incidence of HPV, both DNA and RNA, along with the histological severity of dysplasia. HPV RNA was detected in all but two PCR-positive cases, confirming that the virus exerts E6/E7 mRNA expression in cases of high-grade dysplasia. Out of 19 women given a normal or borderline diagnosis at conisation, only four were found HPV positive, which may suggest that unnecessary conisations can possibly be reduced by introducing HPV testing into the preoperative routine assessment.

HPV Virus Scientific Facts - HPV Research Links

Department of Pathology - Read about investigations of the HPV research group.

HPV and Cervical Cancer - Read about the research on HPV vaccine.