scholarly journals Molecular variants of human papillomavirus types 16 and 18 preferentially associated with cervical neoplasia

2000 ◽  
Vol 81 (12) ◽  
pp. 2959-2968 ◽  
Author(s):  
Luisa L. Villa ◽  
Laura Sichero ◽  
Paula Rahal ◽  
Otavia Caballero ◽  
Alex Ferenczy ◽  
...  

In order to determine geographically related intratypic variation in human papillomavirus (HPV) type 16 and 18 isolates that could be associated with lesion development, data were analysed from an ongoing cohort study of the natural course of infection of HPVs and cervical neoplasia. Testing for HPVs was carried out by PCR and molecular variants of these HPVs were characterized by sequence analysis of the long control region and by dot blot hybridization of the E6 and L1 genes. Tests for HPV were done in multiple first-year specimens from 1690 women enrolled in a cancer screening program from 1993 to 1997. Subjects were followed-up by cytology and cervicography for detection of cervical lesions. Seven variants of HPV-16 and four of HPV-18 were detected in one or more specimens from 65 subjects. The same variant was found in specimens taken on different visits from each case of persistent infection. Overall, non-European variants tended to persist more frequently [odds ratio (OR)=4·5; 95% confidence interval (CI), 1·6–12·4] than European (E) variants (OR=2·5; 95% CI, 1·3–4·9), relative to the risk of persistence for non-oncogenic HPVs. In addition, non-E variants were more strongly associated with risk of both prevalent (age- and race-adjusted OR=172·2; 95% CI, 47·1–630·1) and incident [relative risk (RR)=22·5; 95% CI, 6·0–83·9] high-grade lesions than E variants (prevalent lesions OR=46·3; 95% CI, 15·5–138·0 and incident lesons RR=6·1; 95% CI, 1·3–27·4), relative to the risk for HPV-negative women. Although consistent, the latter differences were not statistically significant. If confirmed in other populations, measurement of intratypic variation of HPV-16 and -18 has the potential to serve as an ancillary tool in cervical cancer screening.

1993 ◽  
Vol 4 (1) ◽  
pp. 13-20 ◽  
Author(s):  
J Monsonego ◽  
L Zerat ◽  
F Catalan ◽  
Y Coscas

To determine the incidence of anogenital papillomavirus infections and to assess the value of available diagnostic methods, we compared the cytological, colposcopic and histological features of anogenital papillomavirus-related lesions with their associated human papillomavirus types (HPV) in 300 women and in their male partners. HPV-type deoxyribonucleic acid was detected by blot hybridization in 398 out of 624 subclinical and clinically defined anogenital lesions. Whatever the site of the lesion, condylomas and low-grade intraepithelial neoplasia (IEN) were found in 84% of lesions associated with HPV 6–11, compared with 32% of lesions containing HPV 16–18 ( P<0.001). Among the HPV 16–18 associated lesions, high-grade cervical, vaginal, vulvar and anal intraepithelial neoplasias represented 45% ( P<0.001) of the lesions. In 65% of 23 cases of squamous anogenital cancer, HPV 16–18 and mixed types were present ( P<0.001). In 54% (161/300) of cases, the lesions were multicentric (161/300). On cytological examination, 27% of the samples gave false negative results. In cervical lesions, there was a good correlation between virological and colposcopic findings, but this was not true for extracervical mucous epithelia in the vagina or on the vulva. With peniscopy in the male partners 220 out of 410 had penile condylomatous lesions and more than half of the 350 male specimens examined by molecular hybridization contained HPV DNA. A correlation was found between the virus types in penile lesions or in cells of the distal urethra and in the cervical lesions of the sexual partner. We concluded that in the majority of cases of cervical lesions there is a correlation between the type of HPV DNA identified by blot hybridization and the cytohistocolposcopic findings. In practice, viral typing may be indicated in cases of colpohistologic discordance and in condyloma low-grade CIN that cannot be distinguished from presumably innocuous human papillomavirus infection.


1998 ◽  
Vol 6 (5) ◽  
pp. 214-219 ◽  
Author(s):  
A. L. Distéfano ◽  
M. A. Picconi ◽  
L. V. Alonio ◽  
D. Dalbert ◽  
J. Mural ◽  
...  

Objective:The aim of this study was to identify human papillomavirus (HPV) in cervical intraepithelial neoplasia (CIN) lesions and to evaluate the persistence of viral DNA after diathermic large loop excision (DLLE) treatment.Study Design:Biopsies from 36 patients with low- and high-grade CIN lesions were studied before and after DLLE treatment looking for HPV sequences. DNA was extracted to perform a radioactive polymerase chain reaction (PCR) using GP 5,6 generic primers. PCR products were analyzed by the single-stranded conformational polymorphism (SSCP) which is a simultaneous detection and typing method. Dot-blot hybridization with generic and type-specific biotinylated oligonucleotide probes was applied in some cases.Results:HPV DNA was found in all pretreatment samples, and the viral type was identified in 80% of them, HPV 16 being the most prevalent. The viral type coincided with that detected in the first biopsy in all except one case. Seventy five percent of the patients (27 cases) were negative for CIN at follow up, but 50% of them remained HPV DNA positive.Conclusion:DLLE treatment was effective in removing the CIN lesion but not the HPV. This fact points out the need to asses the presence of HPV in DNA during the follow-up, since viral persistence has been considered a high risk factor for recurrence and/or malignant transformation.


2010 ◽  
Vol 84 (16) ◽  
pp. 8219-8230 ◽  
Author(s):  
Monika Somberg ◽  
Stefan Schwartz

ABSTRACT Our results presented here demonstrate that the most abundant human papillomavirus type 16 (HPV-16) mRNAs expressing the viral oncogenes E6 and E7 are regulated by cellular ASF/SF2, itself defined as a proto-oncogene and overexpressed in cervical cancer cells. We show that the most frequently used 3′-splice site on the HPV-16 genome, site SA3358, which is used to produce primarily E4, E6, and E7 mRNAs, is regulated by ASF/SF2. Splice site SA3358 is immediately followed by 15 potential binding sites for the splicing factor ASF/SF2. Recombinant ASF/SF2 binds to the cluster of ASF/SF2 sites. Mutational inactivation of all 15 sites abolished splicing to SA3358 and redirected splicing to the downstream-located, late 3′-splice site SA5639. Overexpression of a mutant ASF/SF2 protein that lacks the RS domain, also totally inhibited the usage of SA3358 and redirected splicing to the late 3′-splice site SA5639. The 15 ASF/SF2 binding sites could be replaced by an ASF/SF2-dependent, HIV-1-derived splicing enhancer named GAR. This enhancer was also inhibited by the mutant ASF/SF2 protein that lacks the RS domain. Finally, silencer RNA (siRNA)-mediated knockdown of ASF/SF2 caused a reduction in spliced HPV-16 mRNA levels. Taken together, our results demonstrate that the major HPV-16 3′-splice site SA3358 is dependent on ASF/SF2. SA3358 is used by the most abundantly expressed HPV-16 mRNAs, including those encoding E6 and E7. High levels of ASF/SF2 may therefore be a requirement for progression to cervical cancer. This is supported by our earlier findings that ASF/SF2 is overexpressed in high-grade cervical lesions and cervical cancer.


2021 ◽  
Vol 15 (09) ◽  
pp. 1339-1345
Author(s):  
Richard Tagne Simo ◽  
Arsène G Djoko Nono ◽  
Hervet Paulin Fogang Dongmo ◽  
Paul F Seke Etet ◽  
Bertrand Kiafon Fonyuy ◽  
...  

Introduction: Various Human papillomavirus (HPV) types cause cervical cancer, and represent the primary cause of cancer death in Africa and the second cause of most common cancers in Cameroon. Herein, we determined the prevalence of high-risk HPV types in women and associated cervical cytologic abnormalities in Yaounde, Cameroon. Methodology: A cross-sectional study targeting HPV-positive women aged 20 and over was conducted between March and June 2020 at the Saint Martin de Porres’ Health Centre in Yaounde. HPV tests were performed by PCR for detection of HPVs 16, 18, 33, and 45. The test was performed on 616 women using exfoliated cell specimens; then, we processed on cytological diagnosis with Pap smears on HPV positive specimens. Results: The HPV types tested were detected in 137 participants, of which 38.7% with multiple HPV infections, and the remaining part with single HPV infections of type HPV 16 (28.5%), HPV 18 (17.5%), HPV 33 (10.2%), and HPV 45 (5.1%). Cervical cytologic abnormalities were found in 69.34% of participants including: LSIL (49.63%), HSIL (15.32%), ASC-US (3.66%) and AGC (0.73%). Co-infections with HPV 16 and HPV 18 were significantly associated with HSIL (p = 0.001) lesions, while HPV 45 was more common in participants with normal cytology (p = 0.001). Cervical lesion occurrence was significantly associated with the number of sexual partners (p = 0.02) and history of oral contraceptive pill use (p = 0.001). Conclusions: Our results suggest that HPV 16 and 18 are predominant in Yaounde, and are associated with more severe precancerous lesions.


Author(s):  
Jacqueline M. Mills ◽  
Elizabeth A. Stier

In 1992 Lorincz et al. were the first to evaluate the clinicopathologic correlation with 11 recently identified human papillomavirus (HPV) genotypes: 31, 33, 35, 42, 43, 44, 45, 51, 52, 56, and 58. Using cervical samples from 8 studies that included specimens from 2627 women, HPV genotypes were categorized by the likelihood of association with grades of cervical neoplasia (from normal to cancer). These findings were the basis of the determination that (a) HPV causes cervical cancer, (b) detection of the cancer associated HPV genotypes could identify women at risk for cervical pre-cancer and cancer, and (c) a prophylactic HPV vaccine should include protection against (at least) HPV 16 and 18.


2020 ◽  
pp. 1276-1281 ◽  
Author(s):  
Paul Thistle ◽  
Rabea Parpia ◽  
Debanjan Pain ◽  
Hang Lee ◽  
Justen Manasa ◽  
...  

PURPOSE High-risk human papillomaviruses (hrHPV) are the primary cause of cervical cancer. Human papillomavirus (HPV) vaccination is expected to prevent cervical cancers caused by the HPV types included in vaccines and possibly by cross-protection from other types. This study sought to determine the hrHPV type distribution in women at a rural Zimbabwe hospital. METHODS We implemented a cross-sectional study at the Karanda Mission Hospital. Using the Visual Inspection with Acetic Acid Cervicography technique, clinicians collected cervical swabs from 400 women presenting for screening for cervical cancer. Samples were initially analyzed by Cepheid GeneXpert; candidate hrHPV genotypes were further characterized using the Anyplex II HPV28 Detection Kit. RESULTS Twenty-one percent of the 400 women were positive for a high-risk genotype when using the GeneXpert analyzer; 17% were positive when using the multiplex analysis. Almost two thirds of the hrHPV women had a single DNA type identified, whereas one third had multiple genotypes, ranging from 2 to 5. hrHPV was observed more frequently in HIV-positive than in HIV-negative women (27% v 15%). Of the 113 isolates obtained, 77% were hrHPV genotypes not included in the bivalent or quadrivalent vaccines, and 47% represented DNA types not covered in the nonavalent vaccine. Forty-seven percent of the women with hrHPV harbored a single genotype that was not covered by the nonavalent vaccine. CONCLUSION A large fraction of hrHPV isolates from women participating in a cervical cancer screening program in northern Zimbabwe are DNA types not covered by the bivalent, quadrivalent, or nonavalent vaccines. These findings suggest the importance of characterizing the hrHPV DNA types isolated from cervical neoplasia in this population and determining whether cross-immunization against these genotypes develops after administration of the vaccines in current use.


1998 ◽  
Vol 36 (10) ◽  
pp. 3020-3027 ◽  
Author(s):  
P. E. Gravitt ◽  
C. L. Peyton ◽  
R. J. Apple ◽  
C. M. Wheeler

Amplification of human papillomavirus (HPV) DNA by L1 consensus primer systems (e.g., MY09/11 or GP5+/6+) can detect as few as 10 to 100 molecules of HPV targets from a genital sample. However, genotype determination by dot blot hybridization is laborious and requires at least 27 separate hybridizations for substantive HPV-type discrimination. A reverse blot method was developed which employs a biotin-labeled PCR product hybridized to an array of immobilized oligonucleotide probes. By the reverse blot strip analysis, genotype discrimination of multiple HPV types can be accomplished in a single hybridization and wash cycle. Twenty-seven HPV probe mixes, two control probe concentrations, and a single reference line were immobilized to 75- by 6-mm nylon strips. Each individual probe line contained a mixture of two bovine serum albumin-conjugated oligonucleotide probes specific to a unique HPV genotype. The genotype spectrum discriminated on this strip includes the high-risk, or cancer-associated, HPV genotypes 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 55, 56, 58, 59, 68 (ME180), MM4 (W13B), MM7 (P291), and MM9 (P238A) and the low-risk, or non-cancer-associated, genotypes 6, 11, 40, 42, 53, 54, 57, 66, and MM8 (P155). In addition, two concentrations of β-globin probes allowed for assessment of individual specimen adequacy following amplification. We have evaluated the performance of the strip method relative to that of a previously reported dot blot format (H. M. Bauer et al., p. 132–152, in C. S. Herrington and J. O. D. McGee (ed.), Diagnostic Molecular Pathology: a Practical Approach, (1992), by testing 328 cervical swab samples collected in Digene specimen transport medium (Digene Diagnostics, Silver Spring, Md.). We show excellent agreement between the two detection formats, with 92% concordance for HPV positivity (kappa = 0.78, P < 0.001). Nearly all of the discrepant HPV-positive samples resulted from weak signals and can be attributed to sampling error from specimens with low concentrations (<1 copy/μl) of HPV DNA. The primary advantage of the strip-based detection system is the ability to rapidly genotype HPVs present in genital samples with high sensitivity and specificity, minimizing the likelihood of misclassification.


2016 ◽  
Vol 19 (1) ◽  
pp. 160-166 ◽  
Author(s):  
Gustavo David García Muentes ◽  
Lindsay Karen García Rodríguez ◽  
Ramiro Israel Burgos Galarraga ◽  
Franklin Almeida Carpio ◽  
Juan Carlos Ruiz Cabezas

ABSTRACT: Introduction: Human papillomavirus (HPV) is considered a necessary causative agent for developing oropharyngeal, anal and cervical cancer. Among women in Ecuadorian population, cervical cancer ranks as the second most common gynecological cancer. Not many studies about HPV burden have been published in Ecuador, and genotypes distribution has not been established yet. The little data available suggest the presence of other genotypes different than 16 and 18. Objectives: In the present study, we attempt to estimate the prevalence of HPV 16, HPV 18 and other 35 genotypes among Ecuadorian women undergoing cervical cancer screening. The overall prevalence of HPV infection was also estimated. Methods: Routine cervical samples were analyzed using Linear Array(r) HPV Genotyping test (Roche). Results: A total of 1,581 cervical samples obtained from Ecuadorian women undergoing cervical cancer screening were included in this study. HPV DNA was detected in 689 cervical samples (43.58%). Of these samples, 604 (38.20%) were positive for a single HPV genotype, while another 85 (5.37%) samples were positive for multiple HPV types. Genotype 16 (5.50%) resulted in the most frequently detected type in both single and multiple infections. HPV 33 (4.55%) and HPV 11 (3.80%) occupied the second and the third place in frequency among all detected genotypes. Conclusions: Viral genotypes different from HPV 16 and HPV 18 are frequently detected among Ecuadorian women. The overall prevalence of HPV resulted higher than the one reported in other South American countries with a greater burden in the second and third decades of life.


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