RESUMEN
Several countries are in the process of switching to high-risk human papillomavirus (hrHPV) testing for cervical cancer screening. Given the multitude of available tests, validated assays which assure high-quality screening need to be identified. A systematic review was conducted to answer the question which hrHPV tests fulfil the criteria defined by an international expert team in 2009, based on reproducibility and relative sensitivity and specificity compared to Hybrid Capture-2 or GP5+/6+ PCR-enzyme immunoassay. These latter two hrHPV DNA assays were validated in large randomized trials and cohorts with a follow-up duration of 8 years or more. Eligible studies citing the 2009 guideline were retrieved from Scopus (http://www.scopus.com) and from a meta-analysis assessing the relative accuracy of new hrHPV assays versus the standard comparator tests to detect high-grade cervical intraepithelial neoplasia or cancer in primary screening. The cobas 4800 HPV test and Abbott RealTime High Risk HPV test were consistently validated in two and three studies, respectively, whereas the PapilloCheck HPV-screening test, BD Onclarity HPV assay and the HPV-Risk assay were validated each in one study. Other tests which partially fulfil the 2009 guidelines are the following: Cervista HPV HR Test, GP5+/6+ PCR-LMNX, an in-house E6/E7 RT quantitative PCR and MALDI-TOF (matrix-assisted laser desorption-ionization time-of-flight). The APTIMA HPV assay targeting E6/E7 mRNA of hrHPV was also fully validated. However, the cross-sectional equivalency criteria of the 2009 guidelines were set up for HPV DNA assays. Demonstration of a low risk of CIN3+ after a negative APTIMA test over a longer period is awaited to inform us about its utility in cervical cancer screening at 5-year or longer intervals.
Asunto(s)
Detección Precoz del Cáncer/métodos , Técnicas de Genotipaje/métodos , Técnicas de Diagnóstico Molecular/métodos , Papillomaviridae/aislamiento & purificación , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/virología , Femenino , Humanos , Papillomaviridae/clasificación , Papillomaviridae/genética , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Papillomaviruses (PV) are a remarkably heterogeneous family of small DNA viruses that infect a wide variety of vertebrate species and are aetiologically linked with the development of various neoplastic changes of the skin and mucosal epithelia. Based on nucleotide similarity, PVs are hierarchically classified into genera, species and types. Novel human PV (HPV) types are given a unique number only after the whole genome has been cloned and deposited with the International HPV Reference Center. As of 9 March 2015, 200 different HPV types, belonging to 49 species, had been recognized by the International HPV Reference Center. In addition, 131 animal PV types identified from 66 different animal species exist. Recent advances in molecular techniques have resulted in an explosive increase in the identification of novel HPV types and novel subgenomic HPV sequences in the last few years. Among PV genera, the γ-PV genus has been growing most rapidly in recent years with 80 completely sequenced HPV types, followed by α-PV and ß-PV genera that have 65 and 51 recognized HPV types, respectively. We reviewed in detail the contemporary molecular methods most often used for identification and characterization of novel PV types, including PCR, rolling circle amplification and next-generation sequencing. Furthermore, we present a short overview of 12 and 10 novel HPV types recently identified in Sweden and Slovenia, respectively. Finally, an update on the International Human Papillomavirus Reference Center is provided.
Asunto(s)
Genotipo , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/virología , Animales , Genoma Viral , Humanos , Papillomaviridae/genética , Infecciones por Papillomavirus/veterinaria , Análisis de Secuencia de ADN , Eslovenia , SueciaRESUMEN
BACKGROUND: High-risk human papillomaviruses (HPV) are the main etiological factor of cervical cancer. Cervical intraepithelial neoplasia grade 3 (CIN 3) is the latest pre-invasive stage of cervical cancer, with an approximately 20% progression rate to invasive cervical carcinoma. OBJECTIVE: To establish the pre-vaccination distribution of HPV genotypes in Slovenian women with CIN 3 lesions, in order to assess the potential benefit of prophylactic HPV vaccination in Slovenia, and to provide baseline data for monitoring the potential replacement of HPV genotypes under selective pressure of HPV vaccines. METHODS AND RESULTS: A total of 261 cervical swabs collected from women with histologically confirmed CIN 3 lesions were analyzed using four genotyping methods: the Abbott RealTime High Risk HPV Assay, the Innogenetics INNO-LiPA HPV Genotyping Extra Test, and the in-house PGMY09/11, and CPI/CPIIg polymerase chain reaction (PCR) and sequencing. Of 261 samples, 253 (96.9%) were HPV positive. The most common HPV genotype in CIN 3 lesions in the Slovenian samples was HPV-16 (59.0%), followed by HPV-31 (7.5%), HPV-33 (7.1%), HPV-58 (5.0%), and HPV-51 (4.0%). The presence of more than one HPV genotype was detected in 49/253 (19.4%) samples. Together, HPV-16 and HPV- 18 accounted for 67.4% of CIN 3 lesions in this Slovenian population. CONCLUSION: The high proportion of CIN 3 lesions caused by HPV-16 and HPV-18 should further support the recent decision to include the prophylactic vaccination against HPV in the national vaccination program in Slovenia.
Asunto(s)
Alphapapillomavirus/genética , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/virología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Genotipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Persona de Mediana Edad , Vacunas contra Papillomavirus , Eslovenia , Adulto JovenRESUMEN
PURPOSE OF INVESTIGATION: To compare the detection and distribution of HPV genotypes in paired cervical scrape samples and tumor tissue samples in patients with cervical cancer. METHODS: Forty cervical scrape samples and 40 paired archival or fresh frozen tissue samples were collected from women with cervical cancer. Polymerase chain reaction with GP5+ and GP6+ primers was performed in all samples for HPV DNA detection. All GP5+/GP6+ negative samples were additionally tested using INNO-LiPA HPV Genotyping Extra Test. RESULTS: Overall, 39/40 (97.5%) of CC samples were HPV DNA positive. HPV 16 was found in 24/40 samples, HPV 18 in 5/40 samples. A co-infection with two different HPV genotypes was identified in one cervical scrape specimen, while in tissue samples only single infections were detected. Overall agreement between paired samples was 98.75%. CONCLUSION: The present study has shown that cervical scrape samples are equally useful for HPV genotype determination as tumor tissue samples in patients with cervical cancer. They can be used as accurate clinical samples for detection of HPV genotype causing cervical cancer or for epidemiological molecular studies.
Asunto(s)
Alphapapillomavirus/genética , Biopsia con Aguja , Carcinoma de Células Escamosas/virología , Infecciones por Papillomavirus/diagnóstico , Neoplasias del Cuello Uterino/virología , Frotis Vaginal , Adulto , Anciano , Alphapapillomavirus/aislamiento & purificación , Femenino , Genotipo , Humanos , Persona de Mediana Edad , Neoplasias del Cuello Uterino/patología , Adulto JovenRESUMEN
BACKGROUND: Genital warts (GWs) are the most frequent benign tumors in the anogenital region of both males and females. Human papillomaviruses (HPV) are etiologically associated with the development of virtually all GWs. HPV-6 and HPV-11 are the most commonly detected HPV genotypes, but at least 20 other alpha-HPV genotypes have occasionally been found in GW tissue specimens. OBJECTIVE: There is limited knowledge of GWs in Slovenia. Thus in this study we tested 55 GW tissue specimens collected from the same number of male patients using 2 different PCR protocols to obtain the first data concerning HPV and GWs in Slovenia. MATERIAL AND METHODS: 55 GW tissue specimens were tested for the presence of HPV using PGMY09/PGMY11 and CPI/CPIIg polymerase chain reaction (PCR). HPV genotypes were determined using restriction fragment length polymorphism analysis of PGMY09/11 PCR products or by sequencing of the CPI/CPIIg PCR products. In some GWs, the genotyping results were also confirmed using the Linear Array HPV Genotyping Test. RESULTS: HPV DNA was detected in all 55 tissue specimens of GWs. HPV-6 or HPV-11 was detected in 53 cases of GWs, and HPV-44 and candHPV-91 in one GW each. HPV-6 was detected approximately 4 times more frequently than HPV-11. In addition, HPV-16, HPV-31, HPV-51, HPV-53, HPV-55, candHPV-62, HPV-66, HPV-70, HPV-73, and HPV-84 were detected in some GW specimens. According to the published data, our study is the first to report the presence of candHPV-62 and candHPV-91 in GW tissue specimens. CONCLUSIONS: Our study showed that HPV can be found in virtually all GW tissue specimens obtained from male patients in Slovenia. Because HPV-6 or HPV-11 was detected in 96.4% of GWs studied, it seems that, if a quadrivalent HPV vaccine proves to be effective in males, this vaccine could prevent the great majority of incidental GWs in males in Slovenia.
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Condiloma Acuminado/virología , Genotipo , Papillomaviridae/genética , Enfermedades del Pene/virología , Adolescente , Adulto , Condiloma Acuminado/epidemiología , Condiloma Acuminado/patología , ADN Viral/análisis , Humanos , Masculino , Papillomaviridae/clasificación , Papillomaviridae/aislamiento & purificación , Enfermedades del Pene/epidemiología , Enfermedades del Pene/patología , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Eslovenia/epidemiologíaRESUMEN
PURPOSE OF INVESTIGATION: To establish the efficiency of laser vaporization (LV), large loop excision of the transformation zone (LLETZ) and cold knife conization, done for precancerous cervical lesions, in eliminating high-risk human papillomavirus (HPV) infection. Additionally, we determined whether the same HPV genotype persisted after surgery. METHODS: A total of 214 women were tested for HPV infection by the Hybrid Capture II (HCII) test prior to surgery. HPV-positive women were followed by HCII test ten months after surgery. In persistently HPV-positive women, HPV genotypes were determined by PCR - PGMY09/PGMY11. RESULTS: The HCII test showed elimination of HPV infection after LV, LLETZ and cold knife conization in 67.6%, 86.3%, and 100% (p < 0.05) of women, respectively. In seven (38.9%) women a different HPV genotype was found to be present after surgery, the corrected efficiency thus being 79.4%, 92.7% and 100% (p = NS), respectively. CONCLUSIONS: The three analyzed surgical procedures are effective in eliminating high-risk HPV infection. HPV testing is useful at follow-up, since it can identify a small proportion of women requiring close surveillance and potential treatment.
Asunto(s)
Papillomaviridae , Infecciones por Papillomavirus/cirugía , Displasia del Cuello del Útero/cirugía , Neoplasias del Cuello Uterino/cirugía , Adulto , Conización , Femenino , Genotipo , Humanos , Terapia por Láser , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Reacción en Cadena de la Polimerasa , Lesiones Precancerosas/cirugía , Lesiones Precancerosas/virología , Neoplasias del Cuello Uterino/virología , Displasia del Cuello del Útero/virologíaRESUMEN
BACKGROUND: Persistent infection with a subgroup of at least 15 high-risk human papillomavirus (HPV) genotypes is considered as a necessary although insufficient etiological factor in the development of cervical carcinoma. As a consequence, HPV testing has recently become an important part of the cervical carcinoma screening and detection algorithms. AIM OF THE STUDY: To evaluate the analytical performance of a recently developed polymerase chain reaction (PCR)-based Amplicor HPV test (Roche Molecular Systems) in comparison with the Hybrid Capture 2 HPV DNA test (hc2) (Digene Corporation) for the detection of 13 high-risk HPV genotypes. Inhouse consensus PGMY09/PGMY11 and CPI/IIg PCRs targeting two different HPV genes coupled with HPV genotyping were used as an HPV internal reference standard. MATERIALS AND METHODS: In the retrospective evaluation, 550 cervical scrape specimens with previously established HPV status were included. Additionally, 312 cervical scrape specimens were tested prospectively for the presence of 13 high-risk HPV genotypes by both hc2 and Amplicor HPV test. RESULTS: In the retrospective evaluation, the Amplicor HPV test results agreed almost completely with the HPV internal reference standard results. In the prospective evaluation performed on 312 samples, the concordant Amplicor and hc2 results were obtained in 85.9% of samples tested. CONCLUSION: In our hands, the Amplicor HPV test demonstrated high analytical sensitivity and specificity. The higher analytical specificity of Amplicor in comparison to that of hc2 can be considered clinically useful. Prospective studies with clinical endpoints are urgently needed to assess the clinical utility of the higher analytical sensitivity of the Amplicor HPV test for primary HPV screening and triaging patients with ASC-US.
Asunto(s)
Sondas de ADN de HPV , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Reacción en Cadena de la Polimerasa , Enfermedades del Cuello del Útero/virología , Femenino , Genotipo , Humanos , Papillomaviridae/genética , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/genética , Estudios Prospectivos , Estudios Retrospectivos , Sensibilidad y Especificidad , Frotis VaginalRESUMEN
To elucidate the putative etiologic role of human papillomaviruses (HPV) in oral carcinogenesis, a comparative study was carried out on 62 tissue specimens of oral squamous cell carcinoma (OSCC) and on 62 specimens of histologically normal oral mucosa obtained from the individuals who matched the subjects with OSCC in age, gender, localization of obtained tissue specimens, drinking and smoking habits. Internal control amplification showed that amplifiable DNA was recovered from 59/62 and 61/62 tissue samples of OSCC and normal oral mucosa, respectively. The amplification with two different HPV L1 and one HPV E6 consensus primer sets showed the presence of the HPV DNA genotypes 16, 33, 58 in 5/59 (8.4%) OSCC specimens and HPV genotypes 11, 16, 31, 68 in 4/61 (6.6%) tissue samples of normal oral mucosa tested. In the study in which a comparative examination of the presence of HPV DNA was for the first time performed on the tissue samples of the patients with OSCC and the age- and gender-matched control subjects there was no significant difference in the prevalence of HPV DNA among both study groups. Our results suggest that occasional findings of HPV DNA in OSCC tissue specimens may be the result of an incidental HPV colonization of oral mucosa, rather than of viral infection, and that HPVs play a limited role in the etiopathogenesis of the majority of OSCC.