Detection of human papillomavirus in squamous cell carcinoma of conjunctiva by nested PCR: a case control study in Iran

Squamous-cell carcinoma (SCC) of the eye conjunctiva is a rare tumor. Its link with immune impairment suggests that infectious agents such as human papillomavirus (HPV) may be involved in the etiology of SCC. We conducted a case-control study on 50 SCC cases (mean age: 65.2) and 50 age frequency-matched control patients with lesion-free, normal conjunctival biopsies (mean age: 63.8) obtained from the cancer registry archive at Pathology Department of Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran, where SCC has become the most common conjunctival malignancy. MY/GP nested PCR was performed for HPV detection and E6/E7 consensus primers in combination of type specific primers were used in another nested PCR series for HPV typing. HPV DNA was detected in 46 of 50 samples of squamous cell carcinoma and none of the normal biopsies by nested PCR using primer sets of the HPV consensus L1 region (MY/GP). Subsequently, specimens from the 46 positive cases were subjected to specific PCR. Although 630bp amplicon was produced in 44 of 46 samples (E6/E7 primers), none of the specific HPV PCR reactions for HPV DNA type 16, 18, 31 or 33 resulted in the detection of HPV DNA in the 44 SCC specimens of the conjunctiva. Current results confirm the role of HPV in the etiology of conjunctival SCC. The absence of HPV 16, 18, 31 and 33 in conjunctival SCC in this study raise doubts about the role of genital types of HPV in conjunctival carcinomas.     

基因芯片对人乳头瘤病毒的快速检测和分型

目的针对HPV DNA亚型的异质性,建立HPV DNA亚型的基因芯片快速检测方法,为HPV感染病例提供诊断依据.方法18种HPV DNA亚型(HPV6 、16、18、31、33、35、39、11、45、51、52、53、56、58、42、59、66、68)特异性探针,固定于硝酸纤维素膜制备成基因芯片,生物素标记引物经通用引物介导PCR(GD-PCR)扩增HPV DNA,PCR产物与基因芯片经反向点杂交检测HPV亚型;同时采用荧光定量PCR检测HPV6、11、16和18亚型.结果31例标本中,基因芯片的阳性检出率为74.2%,其中HPV6/18、HPV11/16、HPV33/58和HPV6/11/33多重感染各1例(3.2%);荧光定量PCR阳性检出率为67.7%,与前种方法相比较,漏诊率为6.5%.结论HPV分型基因芯片可1次检测HPV多种亚型,灵敏度高和特异性强,有利于对HPV多重感染的诊断.     

人乳头瘤病毒基因分型芯片的建立及其在临床中的应用

目的 建立一种适合于临床应用的人乳头瘤病毒（HPV）基因分型检测新方法,并通过对宫颈分泌物标本检测,验证HPV基因分型检测新方法的临床使用效果.方法 利用HPV保守的L1区设计各型PCR扩增通用引物,根据GenBank中HPV的型特异性序列设计、合成分型探针,制备可对16、18、31、33、35、39、45、51、52、53、56、58、59、66和68型15种高危型和6、11和42型3种低危型HPV进行联合分型检测的膜芯片.通过对100例宫颈炎患者宫颈分泌物标本进行检测,以了解临床使用效果;对阳性标本进行测序以验证分型的准确性;对标准品进行测定以检测其灵敏度.结果 在100例临床样品中发现HPV感染病例30例,其中包括高危型中的HPV16、18、33、45、51、58和66,以及低危型中的HPV6、11和42,既有单一型感染也有混合型感染.灵敏度经标准品验证可达10个拷贝的HPV DNA分子.对单一类型感染基因测序分型证实,所建立的HPV基因芯片分型结果与测序结果完全一致.结论 利用PCR-膜芯片技术建立的HPV基因分型诊断方法可以简便、有效地检出所有已知的高危型和低危型HPV,并能明确其基因类型,适用于临床HPV感染的实验室诊断与流行病学研究.     

Detection and typing of human papillomaviruses by polymerase chain reaction in cervical scrapes of Croatian women with abnormal cytology

The association between certain human papillomaviruses (HPV) and cervical intraepithelial neoplasia (CIN) is well documented, but still unknown among Croatian women. In 1995, women between the age of 17 and 64 with cytomorphologically abnormal smears (CIN I–IV) were tested for the presence of HPV. Consensus and specific primers were used in the polymerase chain reaction (PCR) to detect the most common types: 6, 11, 16, 18, 31 and 33, as well as the unknown-risk HPV types (HPV X). Out of 379 specimens, 163 (43%) contained one or more HPV types. Coinfection with different HPV types in the same sample was observed in 16 cases. Beside low-risk HPV 6/11 (25.8%) the most frequently observed types were high-risk HPV types 16 (20.2%) and 31 (17.8%). Globally, the HPV positivity rate declines with age. The presence of HPV DNA significantly increased from 35.5 to 61.1% along with the severity of the cervical intraepithelial neoplasia (CIN I– IV). HPV type 6/11 was strongly associated with CIN I (33.8%), HPV type 31 with CIN II (22.9%), and HPV type 16 with CIN III (50%).     

A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men

BackgroundA nine-valent human papilloma virus (9vHPV) vaccine has been developed to prevent infections and diseases related to HPV 6/11/16/18 (as per the licensed quadrivalent HPV (qHPV) vaccine) as well as to five additional oncogenic HPV types (HPV 31/33/45/52/58). The 9vHPV vaccine has the potential to prevent 90% of cervical cancers, HPV-related anal, vaginal and vulval cancers and anogenital warts. We compared the immunogenicity and safety of the 9vHPV vaccine versus the qHPV vaccine in 16–26-year-old men.MethodsParticipants (N = 500) were randomised to receive 9vHPV or qHPV vaccines on day 1, month 2 and month 6. Serology testing was performed on day 1 and month 7. HPV type-specific antibody titres (anti-HPV 6/11/16/18/31/33/45/52/58) were determined by competitive Luminex immunoassay and expressed as geometric mean titres and seroconversion rates. Vaccine safety was also assessed.ResultsThe HPV 6/11/16/18 immune responses elicited by the 9vHPV vaccine were comparable with those elicited by the qHPV vaccine. All participants receiving the 9vHPV vaccine seroconverted for HPV 31/33/45/52/58. The 9vHPV and qHPV vaccines showed comparable safety profiles.ConclusionsIn addition to immune responses to HPV 31/33/45/52/58, a three-dose regimen of the 9vHPV vaccine elicited a similar immune response to HPV 6/11/16/18 when compared with the qHPV vaccine in men aged 16–26 years. The safety profile was also similar for the two vaccines. The results from this study support extending the efficacy findings with qHPV vaccine to 9vHPV vaccine in men aged 16–26 years.NCT02114385     

Detection and molecular typing of human papillomaviruses: prevalence of cervical infection in the Tunisian central region

There are compelling molecular and epidemiological data which indicate that infection with certain genital human papillomaviruses (HPVs), such as HPV 16 and HPV 18, has a critical role in initial changes that lead to cervical and probably other anogenital cancers. These observations prompted us to investigate the prevalence of cervical infection with genital human papillomaviruses in Tunisia. We used the polymerase chain reaction (PCR) to detect and type HPV DNA. The prevalence of HPV infection in a population of 106 Tunisian women recruited at the Offices Nationaux de la Famille et de Population (ONFP) was 13.6%. Molecular HPV typing indicated a high prevalence of HPV at high oncogenic risk; Our results indicate that the infection with genital human papillomaviruses is frequent in the Tunisian population.     

HPV infections among young MSM visiting sexual health centers in the Netherlands: Opportunities for targeted HPV vaccination

IntroductionIn 2009, girls-only HPV16/18 vaccination was introduced in the Netherlands which has achieved 46–61% uptake. Heterosexual men have benefitted from herd protection, but it is unknown whether men who have sex with men (MSM) also benefit from herd effects of the girls-only HPV16/18 vaccination program. Because MSM bear a high HPV-related disease burden, countries might consider targeted vaccination for MSM. To study possible herd effects and prior HPV exposure at a potential moment of vaccination, we assessed trends in the HPV prevalence and proportions (sero)negative for the various vaccine types among young MSM visiting sexual health centers (SHCs).MethodsWe used data from MSM included in PASSYON study years 2009–2017. In this biennial cross-sectional study among visitors of SHCs aged 16–24 years, MSM provided a penile and anal swab for HPV DNA testing (including vaccine types HPV6/11/16/18/31/33/45/52/58) and blood for HPV antibody testing (HPV16/18/31/33/45/52/58).ResultsIn total 575 MSM were included, with a median of 22 years of age and 15 lifetime sex partners and 3.5% HIV positive. Trends in penile or anal HPV prevalence during 2009–2017 were statistically non-significant for all vaccine types. Of the 455 MSM with a penile and anal swab, 360 (79%), 283 (62%) and 242 (53%) were HPV DNA negative at both anatomical sites for HPV16/18, HPV6/11/16/18 and HPV6/11/16/18/31/33/45/52/58 respectively. Among MSM who were HPV16/18 and HPV16/18/31/33/45/52/58 DNA negative and were tested for serology (n = 335 and 279 respectively), 82% and 71% were also seronegative for the respective types.DiscussionThere were no significant declines in the HPV prevalence among MSM up to eight years after introduction of girls-only HPV16/18 vaccination, indicating that MSM are unlikely to benefit largely from herd effects from girls-only vaccination. Most MSM were vaccine-type DNA negative and seronegative, suggesting that vaccination of young MSM visiting SHCs could still be beneficial.     

Detection and typing of human papillomavirus DNA in paired urine and cervical scrapes

The prevalence of human papillomavirus (HPV) in paired cervical scrape and urine specimens from 144 women attending a clinic for genitourinary medicine was determined by polymerase chain reaction (PCR) and nested PCR, using degenerate and general primer pairs localized within the L1 region. HPV typing was by restriction fragment length polymorphism (RFLP), type-specific PCR (HPV 6, 11, 16, 18, 33), and partial DNA sequencing of PCR products. HPV DNA was detected in 114 (84%) women. HPV DNA was detected in the specimens of 58 patients after amplification with MY09/MY11 primers and in a further 54 patients after nested PCR with the GP5 + /GP6 + primers. A total of 106/136 (78%) of women had HPV DNA positive cervical scrapes and 89 (65%) had HPV DNA positive urine specimens. Both the urine and cervical specimens of 81 women were positive. In 25 women HPV DNA was detected in the cervical specimen only, and in 8 women HPV DNA was detected in the urine specimens only. A total of 108 specimens from 75 patients were typed. For 33 patients HPV typing was achieved in both the cervical and the urine specimens and 19 women had identical types in paired specimens. Multiple HPV infections could be detected in 15 (20%) of 75 women where either the cervical and urine specimen or both of the specimens could be typed. More then one HPV type was found in 8 specimens and from multiple sites (cervix and urinary tract) in the same patients on 7 occasions. The results of this study indicate that the detection of HPVs in the urogenital tract can be maximised through the testing of both cervical scrapes and urine specimens in conjunction with the use of a nested PCR to increase the sensitivity of HPV DNA detection. Also, urine cannot be a direct substitute for a cervical scrape as different HPV types are often detected in the urine compared with those detected in the cervix.     

湖南地区尖锐湿疣患者感染HPV类型分析

目的　分析湖南地区尖锐湿疣 (CA)的发病人群及其人类乳头瘤病毒 (HPV)的型别。　方法　采用荧光定量 PCR(fluorescence quantitative polymerase chain reaction,FQ- PCR)技术检测尖锐湿疣皮损中人乳头瘤病毒基因。　结果　 5 0例尖锐湿疣患者年龄 4 0岁以下占 80 %。 5 0例尖锐湿疣标本经 FQ- PCR检测后 4 4例 HPV阳性 ,阳性标本中6 / 11型 4 2例 (84 % ) ,16 / 18型 1例 (2 % ) ,6 / 11和 16 / 18混合阳性 1例 (2 % )。　结论　 HPV6 / 11型感染是湖南地区尖锐湿疣发病的首要原因。感染高峰在年龄 4 0岁以下性活跃人群。     

Prospective follow-up of genital HPV infections: Survival analysis of the HPV typing data

A series of 532 women with genital HPV infections has been prospectively followed-up without treatment since 1981 for a mean of 50 (+/-21) months. The patients were examined at six month intervals by colposcopy, PAP smears and/or biopsy. HPV typing of all biopsies was completed using in situ, Southern blot and/or sandwich hybridization with DNA probes for types 6, 11, 16, 18, 31 and 33. Survival data analysis was applied to analyse the clinical course (i.e. spontaneous regression and progression) of the HPV lesions stratified by their HPV type, currently available for 458 women. Clinical progression was significantly related to the HPV type present in the lesions. The progression rate was 11.1% (6/54) for HPV 6 lesions, 14.3% (8/ 56) for HPV 11, 35.2% (32/91) for HPV 16,12.5% (4/32) for HPV 18,18.8% (6/32) for HPV 31,19.4% (6/31) for HPV 33 and 28.6% (4/14) for doubly infected lesions. The lowest progression rate, 6.1% (9/ 148), was found in lesions which remained constantly HPV DNA-negative. In the survival analysis the probability of progression varied significantly between the six HPV types (p=0.0005, overall). After grouping the viral types as HPV 6/11 (low risk), HPV 16/18 (high risk) and HPV 31/33 (intermediate risk) the overall probability of progression remained significantly different (p=0.0035, overall). In clinical regression, however, the HPV type was not an equally good predictor (p=0.1952, overall). Within groups HPV 6/11, 16/18 and 31/33 the differences were even less significant (p= 0.4759, overall). In the pairwise comparison significant differences in progression occurred when HPV type 16 was compared to HPV 6, HPV 11 or HPV DNA-negative lesions. In regression similar differences existed in comparison of HPV DNA-negative to HPV 6 or HPV 18 lesions.These data confirm the previous finding of HPV type 16 as a high risk type in cervical infections. Types 31 and 33 belong to intermediate category. Although, previously included in the high risk category, type 18 did not markedly differ from the clinical course of the low risk (HPV 6, 11) types in the study.Corresponding author.     

Distribution of human papillomavirus genotypes in plucked eyebrow hairs from Slovenian males with genital warts.

In the present study, the presence and distribution of human papillomaviruses (HPVs) in the plucked eyebrow hairs obtained from 49 Slovenian male patients with genital warts were investigated. Using polymerase chain reaction (PCR) with three sets of degenerate primers targeting all known HPV genotypes, HPV DNA was found in 31 (63.3%) of 49 eyebrow hair samples. Epidermodysplasia verruciformis (EV) associated HPV specific Ma/Ha nested PCR system detected HPVs in 27 (55.1%) and CPI/CPIIs primers that amplify the majority of cutaneous/EV HPV genotypes in 20 (40.8%) of 49 samples tested. The CPI/CPIIg PCR specific for E1 open reading frame of genital HPVs showed the presence of HPV DNA in 10 (20.4%) of 49 specimens. Direct sequencing of the Ha PCR products showed the presence of three putative new HPV genotypes, named SIBX1, SIBX2 and SIBX3. Similarly, three potential new HPV genotypes, SIBX4, SIBX5 and SIBX6, were detected by sequencing CPI/CPIIs PCR products. In total, at least 24 different HPV genotypes were detected in 31 HPV DNA positive samples of plucked eyebrow hairs. The results of our study showed that the use of a combined degenerate primer PCR approach considerably improves the HPV DNA detection over individual primer sets and greatly improves the detection of different HPV genotypes in the plucked eyebrow hairs.     

FQ-PCR方法检测女性CA患者HPV_(6、11)和HPV_(16、18)的实验研究

目的:探讨女性尖锐湿疣(CA)患者HPV6、11型和HPV16、18型的感染情况。方法:采用荧光定量聚合酶链反应(FQ-PCR)方法检测216例女性CA患者疣体组织或分泌物中的HPV6、11型和HPV16、18型。结果:HPV6、11型阳性率为94.91%(205/216),HPV16、18型阳性率为16.20%(35/216),HPV6、11型和HPV16、18型同时阳性的感染率为12.50%(27/216)。定量测定结果显示,HPV6、11型患者病毒载量最高1.0×108 copies/ml,最低2.8×103copies/ml;HPV16、18型患者病毒载量最高1.0×108 copies/ml,最低2.57×104 copies/ml。结论:FQ-PCR技术具有灵敏、简捷、安全、特异性强的特点,避免了单纯PCR扩增产生的假阳性。女性尖锐湿疣患者应用此方法检测HPV阳性率高,可以快速区分高危型及低危型的HPV感染,有助于对尖锐湿疣的复发和癌变作出可能性预测。     

Prevalence of human papillomavirus (HPV)-vaccine types by race/ethnicity and sociodemographic factors in women with high-grade cervical intraepithelial neoplasia (CIN2/3/AIS), Alameda County,California, United States

We evaluated racial/ethnic differences in prevalence of oncogenic HPV types targeted by the quadrivalent HPV vaccine (16/18) and nonavalent HPV vaccine (31/33/45/52/58) in women diagnosed with CIN2/3/AIS after quadrivalent HPV vaccine introduction (2008–2015). Typing data from 1810 cervical tissue specimen from HPV-IMPACT (Alameda County, California, US), a population-based CIN2/3/AIS surveillance effort, were analyzed. Using log-binomial regression, we calculated adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) comparing type prevalence by race/ethnicity, adjusted for health insurance, age, CIN2/3/AIS grade, and time period, overall and in the “early vaccine era” (2008–2011) and “later vaccine era” (2012–2015). Overall, oncogenic HPV16/18 prevalence was significantly lower among black (43%) and Hispanic (43%) women compared with white (52%) women (aPR (95% CI): 0.80 (0.70, 0.93) and 0.80 (0.70, 0.91), respectively). In 2008-2011, proportion of HPV16/18 detected was significantly lower in black (47%), Hispanic (46%), and Asian (42%) women compared to white (58%) women (aPR (95% CI): 0.80 (0.67, 0.96), 0.75 (0.63, 0.90), and 0.73 (0.58, 0.90), respectively). There were no significant differences in 2012-2015. Between the two eras, HPV16/18 prevalence declined in white (−11%), black (−9%), and Hispanic (−6%) women, and increased in Asian women (12%). Decreasing HPV 16/18 prevalence in CIN2/3/AIS lesions in white, black, and Hispanic women may suggest benefit from quadrivalent vaccination. In our unadjusted analysis of HPV31/33/45/52/58, prevalence did not differ significantly by race/ethnicity, but was significantly higher among Hispanic women (32%) compared to white women (27%) after adjustment (aPR (95%CI): 1.22 (1.02, 1.47). Prevalence was also non-significantly higher among black (32%) and Asian (33%) women. This analysis suggests that the nonavalent vaccine’s potential for impact against cervical precancers will not be lower in women of color compared to white women. These data underscore the importance of equitable vaccination in facilitating continued declines of vaccine-preventable HPV types among all women.     

HPV vaccines to prevent cervical cancer and genital warts: an update

Cervical cancer is an important public health problem worldwide, and especially in developing countries. The link between cervical cancer and oncogenic human papillomavirus (HPV) infection has been clearly established. Furthermore, non-oncogenic HPV are responsible for the majority of genital warts. Two prophylactic HPV vaccines are available, which have the potential of considerably reducing HPV-related morbidity and mortality. Both vaccines are based on virus-like particles of the L1 capsid protein, and are highly efficacious and immunogenic if given before exposure to HPV, i.e. to adolescent girls between 9 and 13 years of age in a three-dose schedule. This review describes the immunology of natural HPV infections and the immune response evoked through vaccination. The current duration of protection is 8.4 years with the bivalent vaccine (HPV16/18) and 5 years with the quadrivalent vaccine (HPV6/11/16/18). Research is on-going to evaluate the efficacy of the current vaccines in a two-dose schedule, as compared to the recommended three-dose schedule. To increase the protection, the development and testing of a nine-valent prophylactic HPV vaccine (HPV6/11/16/18/31/33/45/52/58) is being undertaken. Research is also directed towards therapeutic vaccines and the development of a prophylactic L2 vaccine.     

Prevalence of human papillomavirus types in North and Central regions of Mexico

Human papillomavirus (HPV) is a DNA virus linked to mucosal and cutaneous carcinogenesis. More than 200 different HPV types exist. We carried out a transversal study to investigate the prevalence of HPV types in two regions of Mexico. A total of 724 genital and non-genital samples from women (F) and men (M) were studied; 241 (33%) from North-Eastern (NE) and 483 (66%) from South-Central (SC) Mexico. The overall prevalence was 87%. In genital lesions from females, the NE group showed a prevalence of HPV types 16 (37%), 6 (13%), 59 (6%), 11, 18 and 66 (5.4% each); and the SC group showed types 6 (17%), 16 (15%), 11 (14.5%), 18 (12%) and 53 (6%). In the genital lesions from males, NE group showed types 16 (38%), 6 (21%), 11 (13%) and 59 plus 31 (7.5%) and the SC group showed types 6 (25%), 11 (22%), 18 (17%) and 16 (11.5%). When the two regions were compared, a higher prevalence of low-risk HPV 6 and 11 was found in the SC region and of high-risk HPV 59, 31 and 66 (the latter can also be present in benign lesions) in the NE region. Our findings complement efforts to understand HPV demographics as a prerequisite to guide and assess the impact of preventive interventions.Key words: Cervical cancer, genotyping, HVP types, Mexico regions     

高危型HPV在宫颈癌发生中的作用

本文利用PCR技术检测了44例宫颈癌患者和15例慢性宫颈炎患者病变组织中高危型HPV（16，18，31，33）的感染率，发现44例宫颈癌患者高危型HPV的阳性率高达91％（40／44），其中HPV16型感染率54．55％（24／44），HPV18型感染率18．2％（8／44），HPV31型感染率13．6％（6／44），HPV33型感染率4．55％（2／44）；15例慢性宫颈炎患者有2例感染HPV16型。结果提示HPV16型是宫颈癌发生最常见的基因型，其次为HPV18型和HPV31型，故对育龄妇女定期进行高危型HPV感染的普查，在早期预防宫颈癌的发生具有十分重要的意义；联合采用分子生物学和宫颈脱落细胞学技术进行即定期普查，既能提高阳性率，又能对感染高危型HPV的慢性宫颈炎患者进行早期的有效预防。     

端粒酶活性、HPV 16/18感染及致癌基因与宫颈癌的关系

目的:探讨端粒酶活性、HPV 16/18感染及致癌基因与宫颈癌的相关性。方法:对40例浸润型宫颈癌,110例宫颈上皮内瘤变(C INⅢ32例、C INⅡ40例、C INⅠ38例)及30例正常者的宫颈新鲜组织,用TRAP—PCR检测端粒酶活性、用FQ—PCR检测HPV l6/18DNA、用PCR方法对HPV 16/18 DNA阳性组织作HPV 16型致癌基因E 6、E 7检测。结果:宫颈癌组中端粒酶阳性38例(95.00%)(HPV 16/18+39例,17例有E 6、E 7表达),端粒酶阴性2例(HPV 16/18+1例,无E 6、E 7表达):C INⅢ级中端粒酶阳性28例(87.5%)(HPV 16/18+30例,22例有E 6、E 7表达),端粒酶阴性4例(2例HPV16/18+);C INⅡ级中端粒酶阳性12例(30%)(HPV 16/18+16例,4例有E 6、E 7表达),端粒酶阴性28例(4例HPV 16/18+);C INⅠ级中端粒酶阳性3例(7.89%)(HPV 16/18+5例,无E 6、E 7表达):而30例正常宫颈组织仅有2例(6.67%)端粒酶活性表达,1例HPV也为阳性而无E 6、E 7表达。宫颈癌和癌前病变(C INⅢ)组织端粒酶活性表达频率(P<0.01)和HPV 16/18感染率(P<0.01)及其致癌基因表达(P<0.01)显著高于良性病变(C INⅠ和C INⅡ)和正常对照。结论:端粒酶活性在宫颈癌发生中可能起到重要作用,在子宫颈损伤中端粒酶激活与HPV感染及其致癌基因的表达密切相关;对于探讨宫颈病变的进展和宫颈癌的发生发展具有重要意义。     

Human papillomaviruses in Amerindian women from Brazilian Amazonia

We evaluated the prevalence of human papillomavirus (HPV) infection in Amerindian women from a tribe in Brazilian Amazonia. Demographic data, pap smears and cervical samples for HPV DNA detection by polymerase chain reaction (PCR) were obtained for women aged above 10 years old. In total, 79 (85.9%) out of 92 eligible women who lived there were interviewed; all women already had engaged in sexual activity. Seventy-eight and 49 women allowed collection of pap smears and PCR samples, respectively. Cytological signs of HPV infection were observed in 11 patients; 6 of these were probed for HPV infection and 1 shown to be HPV 16. Overall prevalence of HPV infection detected by PCR was 14.3%. Three patients presented high-risk HPV DNA types:two HPV 16 and one co-infection of HPV 16 and 58. Cervical infection by oncogenic HPV types occurs in Amerindian women and cervical cancer screening should be a priority in this setting.     

人乳头状瘤病毒快速导流杂交与传统杂交法比较基因分型及临床应用

目的利用快速导流杂交法对人乳头瘤病毒进行快速基因分型,并探讨该技术临床应用前景. 方法 144例尖锐湿疣患者皮损脱落细胞或组织中提取DNA,PCR扩增后与9种常见HPV亚型探针进行反斑点印迹杂交(reverse dot blot, RDB)检测HPV DNA,通过与传统膜杂交结果做对比,评估导流杂交法的效果. 结果 144例样本中得到134例PCR阳性结果;HPV分型包括:高危HPV亚型16、18、31、33、58;低危亚型6、11、53;未知危险程度的亚型CP8304;68例样本中包括了2～4种亚型的混合感染. 结论两种杂交方法检测结果97%一致;快速导流法优势主要具有更高速度、操作更方便,和节省试剂用量;敏感性和特异性与传统杂交方法相同.     

Immunogenicity and safety of a nine-valent human papillomavirus vaccine in women 27–45 years of age compared to women 16–26 years of age: An open-label phase 3 study

BackgroundEfficacy of the nine-valent human papillomavirus (9vHPV; HPV types 6/11/16/18/31/33/45/52/58) vaccine was demonstrated in a phase 3 study in women 16–26 years of age. We present a phase 3 immunogenicity and safety study of the 9vHPV vaccine in women 27–45 versus 16–26 years of age.MethodsThis international, open-label study (NCT03158220) was conducted in women 16–45 years of age. Participants (16–26 years, n = 570 and 27–45 years, n = 642) received a three-dose 9vHPV vaccination regimen (day 1, month 2, month 6). Month 7 geometric mean titers (GMTs) and seroconversion percentages to anti-HPV 6/11/16/18/31/33/45/52/58 were assessed. Participants were followed for safety throughout the study.ResultsAt month 7, anti-HPV 6/11/16/18/31/33/45/52/58 GMTs in women 27–45 years were compared to those in women 16–26 years of age. The primary hypothesis of non-inferiority of anti-HPV 16/18/31/33/45/52/58 GMTs in older versus younger women was met. The lower bound of the GMT ratio 95% confidence interval (27–45 years to 16–26 years) was 0.60–0.67 depending on HPV type, exceeding the non-inferiority margin of 0.5 for all HPV types. Month 7 seroconversion percentages in women 27–45 years of age were >99% for all HPV types. Injection-site and vaccine-related systemic adverse events (AEs) were observed in 87.5% and 25.1% of women 16–26 years, and 85.2% and 24.1% of women 27–45 years of age, respectively; no vaccine-related serious AEs were reported and no deaths occurred during the study.ConclusionsThe 9vHPV vaccine elicited non-inferior anti-HPV GMTs in women 27–45 years compared with women 16–26 years of age for HPV 16/18/31/33/45/52/58. The vaccine was generally well tolerated with a similar AE profile across the age groups. These data support bridging 9vHPV vaccine efficacy findings in women 16–26 years to women 27–45 years of age.Clinical trial registration NCT03158220.