Gardasil™ HPV vaccination: surveillance of vaccine usage and adherence in a military population

Objectives

To investigate the usage patterns and adherence rates with the quadrivalent HPV (qHPV) vaccine at Naval Medical Center San Diego.

Methods

This retrospective, cross-sectional study was conducted by using AHLTA (Electronic Health Record of DoD) to identify all qHPV recipients between 2006 and 2009. Charts were reviewed to extract demographic variables and immunization schedules for association analysis. Subjects were assigned intention-to-treat (ITT) if they initiated the series and reached the 1-year anniversary after dose-1 or in-progress (IP) if the series was incomplete and within 1-year. ITT subjects were designated non-adherent or adherent based on 1–2 or 3 doses received.

Results

6792 females and 46 males with respective mean ages (years) of 19 (95% CI: 10–29) and 27 (95% CI: 9–46) initiated the qHPV series. The evaluable ITT population consisted of 5088 females and 31 males. The adherence rate for females was 32% (1656/5088) versus 3% (1/31) for males. For females, adherence declined from 45%, 24%, to 14% with respect to increasing age: 8–17, 18–26, 27–50 years. Adherence declined accordingly by beneficiary status: dependent daughters (43%), spouses (21%) and active duty (16%); and by clinic of vaccine initiation: Pediatrics/Adolescent (45%), Primary Care (38%), Immunization (21%), and OB/GYN (9%). Males were predominantly active duty 84%, vaccinated through immunization clinics 84%, and poorly adherent 3%.

Conclusions

Optimal HPV immunization efficacy is derived from vaccine adherence and HPV naivety. This study of qHPV adherence has provided insight into real-world suboptimal use post-marketing. Usage patterns and adherence rates were significantly associated with demographic characteristics.     

人乳头瘤病毒预防性疫苗及其策略展望

宫颈癌是中国女性最常见的肿瘤之一.人乳头瘤病毒(HPV)感染是宫颈癌及其癌前病变的必要因子.HPV的病毒样颗粒(由HPV病毒基因组L1基因编码)可产生中和抗体,其结果是HPV病毒样颗粒的注射可有效地预防某个HPV型别的感染.由于HPV16和18两个型别在宫颈癌中具有较高的流行率,这两个型别的病毒样颗粒已被开发成为预防性...     

河南地区妇女宫颈病变HPV型别分布研究

目的：统计各型人乳头瘤病毒（HPV）在子宫颈癌和宫颈上皮内瘤变（CIN）Ⅱ以上病例中的分布数据,为HPV疫苗引入中国以及在中国开展HPV疫苗效果评价的四期临床试验提供基线资料。方法：采用“三明治”技术进行病理切片,并运用SPF10-聚合酶链反应（PCR）技术进行DNA扩增,再利用DNA酶免疫测定法（DEIA）和包括25种型别特异性探针的反向杂交线型探针检测技术（LiPA）对HPV阳性标本进行HPV分型检测。结果：91例宫颈组织样品（包括13例CINⅡ,36例CINⅢ,40例鳞状细胞癌,2例腺鳞癌）,通过DEIA检测时,HPV均为阳性,阳性率100%;通过LiPA检测时,HPV阳性89例,阳性率97.8%,以HPV-16为主,其次是HPV-58,HPV-18和HPV-31。其中单一型感染72例,双重感染11例,多重感染6例。结论：河南地区宫颈病变患者组织中HPV感染主要为单一型感染,以HPV-16和HPV-58为主,为目前已研制成功的预防性疫苗在中国开展人群疫苗干预提供了理论基础,同时,HPV-58在研究人群中的重要性也对新型疫苗的开发提出挑战。     

植酸酮对人宫颈癌细胞增殖的影响

目的：研究不同浓度植物提取物植酸酮在不同作用时间对两种宫颈癌细胞系增殖的影响。方法：以培养基稀释植酸酮妇科清洗装置Ⅱ型1号及2号至相应浓度,采用噻唑蓝（MTT）比色法检测不同药物浓度对宫颈癌HeLa细胞[腺癌,含人乳头状瘤病毒18（HPV18）基因]及Caski细胞（鳞癌,含HPV16基因）不同时间点的增殖抑制率。结果：植酸酮妇科清洗装置Ⅱ型1号及2号试剂对HeLa及Caski细胞增殖的抑制作用具有浓度依赖性和时间依赖性。不同浓度植酸酮妇科清洗装置Ⅱ型1号及2号试剂对HeLa及Caski细胞增殖抑制作用差异有统计学意义（P＜0.05）,细胞增殖抑制率随给药浓度增加作用增强,浓度为5 860 mg/L、5 500 mg/L细胞增殖抑制率最高。同一给药浓度不同作用时间对细胞增殖抑制率差异具有统计学意义（P＜0.05）。结论：植酸酮对宫颈癌细胞系增殖具有抑制作用,可为临床上植酸酮抗HPV治疗宫颈病变及宫颈癌提供理论依据。     

HPV单一感染与多重感染对宫颈病变影响的比较

目的：探讨单一高危HPV亚型与多重高危HPV亚型感染对宫颈病变的影响。方法：选取2010年1月—12月在天津医科大学总医院妇科门诊就诊的有性生活史并出现临床症状的患者137例,比较患者细胞学、病理学结果出现的概率;比较单一高危HPV亚型与多重高危HPV亚型感染对宫颈病变影响的差别。结果：①在全部感染病例中,以20～49岁者居多,并且随着年龄的增长,感染率呈现下降趋势。②感染病例中,高危型别以HPV16感染率最高。③在宫颈高级别病变中,以HPV16感染率最高。④单一高危与多重高危HPV感染相比较,宫颈细胞学和病理学结果差异无统计学意义。⑤高低危混合HPV感染中低级别病变概率高于单纯高危HPV感染,而高级别病变则相反。结论：①与单一高危HPV亚型相比,多重高危HPV亚型感染对宫颈病变严重程度的影响不明显。②与单纯高危HPV亚型感染相比,高低危HPV亚型混合感染更多表现为低级别宫颈病变。     

宫颈上皮内瘤变及早期宫颈癌组织中P16、HPV L-1壳蛋白的表达及与HR-HPV载量相关性研究

目的:探讨宫颈上皮内瘤变(CIN)及早期宫颈癌组织中P16、HPV L-1壳蛋白的表达及与高危型人乳头瘤病毒(HR-HPV)载量的相关性。方法:分别采用免疫组化法和第二代杂交捕获法(hybrid captureⅡ,HC-2)检测26例慢性宫颈炎组织、83例低度鳞状上皮内病变(LSIL)(CINⅠ83例)、109例高度鳞状上皮内病变(HSIL)(CINⅡ49例,CINⅢ60例)、11例早期宫颈鳞癌组织中P16蛋白、HPV L-1壳蛋白的表达及HR-HPV载量,并分析其相关性。结果:1在宫颈癌前病变中随病变级别增高,HR-HPV阳性率增加,差异有统计学意义(P0.01)。各组织学分级中病毒载量分布差异有统计学意义,HSIL(44.95%)及早期宫颈癌组织(63.64%)中皆以低病毒载量(1~100 RLU/CO)为主。从慢性宫颈炎、LSIL、HSIL到早期宫颈癌,P16蛋白阳性表达率分别为11.54%(3/26),55.42%(46/83),85.32%(93/109),100.00%(11/11),差异有统计学意义(P0.01);L-1壳蛋白阳性率分别为15.38%(4/26),28.92%(24/83),14.68%(16/109),0.00%(0/11),差异有统计学意义(P0.05)。2229例宫颈组织中,随HPV载量增加,P16蛋白表达增强;L-1壳蛋白阳性表达率增加,差异有统计学意义(P0.01)。3在慢性宫颈炎组中,P16蛋白阳性表达与HPV载量呈正相关(r=0.491,P0.05)。在LSIL组中,P16蛋白与HPV载量(r=0.459,P0.01)及L1壳蛋白表达(r=0.297,P0.01)皆呈正相关。4在HSIL及早期宫颈癌组中,P16蛋白、L-1壳蛋白表达与HPV载量三者之间无明显相关性(P0.05)。结论:P16、HPV L-1壳蛋白异常表达是宫颈癌前病变发生发展的早期分子事件,对判断CINⅠ有参考价值,可能比HR-HPV载量更具有预测价值。     

Age-specific detection of high risk HPV DNA in cytologically normal, computer-imaged ThinPrep Pap samples

OBJECTIVE: Recent cervical cancer screening guidelines for women over age 30 seek to improve the sensitivity of cytology by incorporating high-risk (HR) human papillomavirus (HPV) DNA testing into the screening algorithm, a recommendation based largely on data that utilized the conventional Pap smear and were not stratified by patient age. Data on the rate of HR HPV among women over age 30 undergoing liquid-based Pap test screening are limited. The objective of this study was to determine the rate of HR HPV DNA positivity in women ages 30 and over with a cytologically negative liquid-based Pap test result. METHODS: Consecutive residual ThinPrep Pap samples from women with a cytologically negative result following computer-assisted screening were tested for HR HPV using the Hybrid Capture 2 (HC2) method. All HC2-positive samples were additionally tested with the Linear Array (LA) HPV Genotyping Test. RESULTS: 1000 cytologically negative specimens from women aged 30 to 45 years (38.9+/-4.7 years) were evaluated. The overall HC2 HR HPV positivity rate in this age group was 3.9% (confidence interval 2.8-5.3%). When stratified by age group, the rate was inversely proportional to age (ages 30-35: 6.7%; 36-40: 3.0%; 41-45: 2.6%) and lower than most previous reports (1-17%). Some of the cases that were positive for HR HPV by HC2 were negative by LA, or showed only low-risk virus. CONCLUSIONS: The HR HPV rates in women ages 30-45 with a cytologically negative, computer-imaged ThinPrep test result are low. If these findings are confirmed in future studies, the added benefit of HPV testing to liquid-based cytology for women ages 30 and over should be critically evaluated.     

Clinical management of women presenting with field effect of HPV and intraepithelial disease

Anogenital human papillomavirus is the most common sexually transmitted infection acquired through skin-to-skin contact. Most infections are cleared by an intact immune system. Persistence of these infections results in precancerous lesions and, eventually, to cancers of the cervix, vagina, vulva, and perianal area. The introduction of the prophylactic human papilloma virus (HPV) vaccinations may reduce the incidence of these infections, but the effect of these vaccinations will be seen only in the decades that follow. In the meantime, multiple therapies such as immune modulators, ablative modalities, and surgical excision are used in an attempt to treat precancerous lesions and hence prevent cancer. There is an increase in multicentric disease in young women, especially with the HIV epidemic and in women who are immune compromised. This article aims to address the challenges and management options in women who have a field effect of HPV-associated disease.     

宫颈癌的相关免疫治疗及进展

宫颈癌是最常见的妇科恶性肿瘤,严重威胁女性健康。高危型人乳头瘤病毒（human papillomavirus,HPV）持续感染是宫颈癌的主要危险因素。近年来,HPV疫苗在宫颈癌预防方面取得了良好的效果,免疫治疗也成为了宫颈癌治疗的新模式,尤其对于手术、放化疗效果不佳和术后转移及晚期复发的患者,免疫治疗尤为重要。免疫治疗的策略主要包括免疫检查点抑制剂、疫苗治疗、树突状细胞免疫疗法和过继细胞免疫疗法。目前,相关的免疫疗法在宫颈癌及其癌前病变治疗的研究中均取得了不错的疗效。综述宫颈癌中的免疫治疗进展,并对今后的研究方向做出展望,从而为宫颈癌的临床治疗和基础研究提供依据。     

The health care costs of cervical human papillomavirus--related disease

OBJECTIVE: The purpose of this study was to examine the health care costs of cervical human papillomavirus-related disease in a US health care setting. STUDY DESIGN: We conducted an observational cohort study using 1997 through 2002 administrative and laboratory records from 103,476 female enrollees of the Kaiser Permanente Northwest health plan (Portland, Ore). We examined the cost per case and annual cost per 1000 enrollees for cervical human papillomavirus-related events. RESULTS: A cervical examination with a normal routine papanicolaou smear incurred costs of 57 dollars (95% CI, 57-57). Costs that were associated with abnormal routine screening diagnoses ranged from 299 dollars for atypical squamous cells (95% CI, 245-352) to 2349 dollars for high-grade squamous intraepithelial lesion (95% CI, 1,047-3,650). The costs of histologically confirmed cervical intraepithelial neoplasia ranged from 1026 dollars for cervical intraepithelial neoplasia 1 (95% CI, 862-1191) to 3235 dollars for cervical intraepithelial neoplasia 3 (95% CI, 2051-4419); a cost of 376 dollars (95% CI, 315-436) was associated with false-positive test results. At the level of the health plan, overall annual cervical cancer prevention and treatment costs were 26,415 dollars per 1000 female enrollees, with routine cervical cancer screening accounting for expenditures of 16,746 dollars per 1000 female enrollees, cervical intraepithelial neoplasia accounting for expenditures of 4535 dollars per 1000 female enrollees, cervical cancer accounting for expenditures of 2629 dollars per 1000 female enrollees, and false-positive test results accounting for expenditures of 2394 dollars per 1000 female enrollees. CONCLUSION: These are the first direct estimates of both individual and population level costs of cervical human papillomavirus-related disease in a general US health care setting. Routine cervical cancer screening comprises nearly two thirds of total annual cervical human papillomavirus-related health care costs, with 10% of expenditures dedicated to the treatment of invasive cervical cancer, 17% to the management of cervical precancers, and 9% to dealing with false-positive Papanicolaou test results.     

Prospective evaluation of longitudinal changes in human papillomavirus genotype and phylogenetic clade associated with cervical disease progression

Objective

Changes in the HPV genotype detected in patients over time could alter cervical disease progression. Identification of patterns in the alteration of HPV genotype should also be related to cytological and histological findings. Thus, we assessed the risk for low-grade squamous intraepithelial lesion (LSIL) or high-grade SIL (HSIL)/squamous cell carcinoma (SCC) associated with alterations in the HPV genotype detected, presence of multiple HPV genotypes, and individual genotyping or HPV clade grouping.

Methods

The 1052 participants were monitored by HPV chip and Pap smear. We calculated odds ratios and applied sequential association analysis (SAA) and decision tree analysis (DTA).

Results

We classified HPV alteration as persistence, regression (spontaneous vs. therapeutic), or metatyping (progressive vs. regressive). Spontaneous regression occurred in 71.9% of patients. Metatyping was strongly associated with progression (RR: 3.9, p = 0.0242), with progressive metatyping showing a higher risk of progression (RR: 31.49, p = 0.00448). Few patients with multiple infections were identified in the initial screen but 30.8% of patients had multiple infections in the final analysis. HPV-16, -35, -52, and -58 were commonly associated with HPV persistence. Univariate analysis determined that final diagnosis significantly associated with HPV type at the endpoint (p < 0.0001), persistence (p = 0.0001), and progressive metatyping (p = 0.0022). SAA determined that HPV-66, -68, and -69 were significantly associated with HSIL, and HPV-16 and -18 persistence significantly association with SCC. DTA indicated an age less than 28 years had a peak in LSIL, and an age between 32 and 48 years had a peak in HSIL. A bimodal peak in SCC for HR-2 at the endpoint was observed in participants less than 32 and greater than 48 years of age.

Conclusions

The alteration patterns of HPV infection detected included persistence, regression, and metatyping. HPV persistence and progressive metatyping are significant signatures of disease progression.     

人乳头状瘤病毒16型多肽疫苗的制备及体内外效应观察

目的 探讨人乳头状瘤病毒(HPV)16型多肽疫苗的制备,并观察HPV16多肽疫苗的体内外效应.方法 (1)针对抗原加工相关转运子(TAP)设计HPV16 E7蛋白的主要组织相容性复合物Ⅰ类分子(MHC-I)的抗原结合表位,利用生物信息学分析平台筛选出一致性较高、特异性及亲和力较强的HPV16 E7多肽作为研究对象制备HPV16多肽疫苗用于以下研究,本研究共筛选出3段多肽,分别命名为E7Pa、E7Pb、E7Pc.(2)C57BL/6小鼠注射鼠肺上皮细胞株TC-1细胞(为鼠源性的HPV16阳性的肿瘤细胞株)后,采用等额抽取的随机方法分为5组,ETPa+二核苷胞嘧啶(CpG)、E7Pb+CpG、E7Pc+CpG[均为实验组,分别加入终浓度为50μg/ml的E7Pa、E7Pb、E7Pc和终浓度为12 mg/L的刀豆蛋白(ConA)]、CpG(为阳性对照,加入终浓度为12 mg/L 的Con A)和空白对照组(不做任何处理).采用四甲基偶氮唑蓝(MTT)比色法检测各组作用不同时间后小鼠脾T淋巴细胞的体外增殖效应,乳酸脱氢酶(LDH)释放法检测小鼠脾T淋巴细胞在不同效靶比下的体外细胞毒T淋巴细胞(CTL)活性,实时荧光定量RT-PER技术检测小鼠肿瘤组织中γ干扰素(IFN-γ)、白细胞介素2(IL-2)mRNA的表达水平,酶联免疫吸附试验(ELISA)检测小鼠外周血中IFN-γ、IL-2的表达水平,通过定期测量比较各组小鼠接种HPV16多肽疫苗后体内肿瘤体积的变化.结果 (1)本研究筛选出了一致性较高、特异性及亲和力较强的3段HPV16 E7多肽作为研究对象制备HPV16多肽疫苗,分别命名为E7Pa、E7Pb、E7Pc.(2)MTT比色法检测显示,在接种疫苗24、48、72、96 h后,以E7Pa+CpG组的增殖效应最明显,其细胞增殖率分别为(131±32)%、(302±15)%、(552±28)%、(731±24)%,明显高于空白对照组的(72±15)%、(120±57)%、(176±41)%、(288±29)%(P<0.01);E7Pb+CpG、ETPc+CpG、CpG组的细胞增殖率也均明显高于空白对照组(P<0.05);但E7Pb+CpG、E7Pc+CpG、CpG组间比较,差异则无统计学意义(P>0.05).LDH释放法榆测显示,效靶比为100:1时,E7Pa+CpG、E7Pb+CpG、E7Pc+CpG、CpG和空白对照组CTL 活性分别为(85.9±3.0)%、(55.9±2.5)%、(60.2±1.5)%、(41.0±1.7)%和(4.1±1.0)%,E7Pa+CpG组与空白对照组比较,差异有统计学意义(P<0.01);E7Pb+CpG、E7Pc+CpG、CpG组分别与空白对照组比较,差异也有统计学意义(P<0.05);但E7Pb+CpG、E7Pc+CpG、CpG组间比较,差异则无统计学意义(P>0.05).在肿瘤组织及外周血中,小鼠IFN-γ、IL-2的表达水平,E7Pa+CpG组与空白对照组比较,差异均有统计学意义(P<0.01);E7Pb+CpG、E7Pc+CpG和CpG组分别与空白对照组比较,差异也均有统计学意义(P<0.05);但E7Pb+CpG、E7Pc+CpG、CpG组问比较,差异则无统计学意义(P>0.05).小鼠体内的肿瘤体积,各实验组肿瘤生长均明显被抑制,接种后第60大,E7Pa+CpG组与空白对照组比较,差异有统计学意义(P<0.01);E7Pb+CpG、E7Pc+CpG和CpG组分别与空白对照组比较,差异也均有统计学意义(P<0.05);但 E7Pb+CpG、E7Pc+CpG、CpG组间比较,差异则无统计学意义(P>0.05).结论 在动物模型中,针对TAP筛选的HPV16 E7多肽联合CpG制备的HPV16多肽疫苗,可以有效治疗HPV16 E7阳性的肿瘤.     

广西4874例妇女高危型人乳头瘤病毒感染的流行病学现状及其与宫颈上皮内瘤变的关系

目的:调查广西妇女生殖道高危型人乳头瘤病毒(HPV)感染现状及与宫颈上皮内瘤变(CIN)的关系。方法:应用第二代杂交捕获(HC2)或HPV基因分型检测技术,对4874例妇女进行HPV检测,高危型HPV感染者进行宫颈活组织检查。结果:①两种方法检测后,HPV阳性率为27.00%(1316/4874),其中高危型HPV阳性率为23.78%(1159/4874),低危型HPV阳性率为3.22%(157/4874)。高危型HPV阳性者CIN57例,占4.92%(57/1159),CINⅡ～Ⅲ29例,占2.50%(29/1159)。②HC2检测结果:检测2260例,其中高危型HPV阳性率24.96%(564/2260)。高危型HPV阳性者CIN29例,占5.14%(29/564),CINⅡ～Ⅲ15例,占2.66%(15/564)。并且,病毒负荷量<100ng/L的CINⅠ、CINⅡ～Ⅲ与病毒负荷量>100ng/L比较,差异有高度统计学意义(χ2=21.098,P=0.000)。③HPV基因分型检测结果:检测2614例,HPV阳性率28.77%(752/2614),其中高危型HPV阳性率为22.76%(595/2614)...     

Methylation of HPV16 genome CpG sites is associated with cervix precancer and cancer

Objective.

Invasive cervix cancer (ICC) is the second most common malignant tumor in women. Human papillomavirus 16 (HPV16) causes more than 50% of all ICC and is a major cause of cervix intraepithelial neoplasia (CIN). DNA methylation is a covalent modification predominantly occurring at CpG dinucleotides. Such epigenetic modifications are associated with changes in DNA-protein interactions and gene activation. This study examined the association of viral and host genomic methylation patterns and cervix neoplasia.

Methods.

Exfoliated cervical lavage samples positive for HPV16 from women with and without cytomorphic changes of infection (n = 46), CIN2 (n = 12), and CIN3+ (n = 27) were used to interrogate the methylation patterns of the HPV16 L1 gene and upstream regulatory region (URR), five host nuclear genes (TERT, RARB, DAPK1, MAL, and CADM1), and mitochondrial DNA (mtDNA). DNA isolated from exfoliated cervicovaginal cells was treated with bisulfite, specific regions of the viral and host genome were PCR amplified and CpG methylation was quantified using EpiTYPER and pyrosequencing.

Results.

Methylation at 14 of the tested CpG sites within the HPV16 L1 region were significantly higher in CIN3+ compared to HPV16 genomes from women without CIN3+. In contrast, 2/16 CpG sites in HPV16 URR, 5/5 in TERT, 1/4 in DAPK1 and 1/3 mtDNA, and 2/5 in RARB were associated with increased methylation in CIN3+.

Conclusions.

These results indicate that increased methylation of CpG sites in the HPV16 L1 ORF is associated with CIN3+ and, thus, may constitute a potential biomarker for precancerous and cancerous cervix disease.     

A phase II trial of interleukin-12 in patients with advanced cervical cancer: clinical and immunologic correlates. Eastern Cooperative Oncology Group study E1E96

PURPOSE: The ability to mount lymphoproliferative responses to peptides derived from the human papillomavirus (HPV) E6 and E7 oncoproteins has been associated with regression of dysplastic lesions of the uterine cervix and loss of associated HPV infection. Interleukin-12 (IL-12) is a potent immunopotentiator of T-cell function, and has been shown in phase I clinical trials to be tolerable. EXPERIMENTAL DESIGN: Patients were required to have measurable metastatic, recurrent or inoperable cervical carcinoma. Patients could have had one prior adjuvant regimen and one prior regimen for advanced disease. Treatment consisted of IL-12 administered at 250 ng/kg IV as a rapid push in the outpatient setting daily x 5 every 21 days. Whole blood samples were acquired twice before treatment then approximately every 3 weeks to assess lymphoproliferative response in vitro to HPV type 16 (HPV 16) E4, E6, and E7 peptides. These responses were correlated with demographics and with clinical outcome. RESULTS: Thirty-four patients were enrolled; 29 were evaluable. Over half had received cisplatin-based chemotherapy. The most common serious toxicities were hematologic or hepatic, and all were reversible. There was one partial responder (3%). The median survival was 6.5 months (95% CI: 5.8, 11.5 months). Eighteen of 29 eligible patients had evaluable laboratory data both pre- and post-therapy. There was a statistically significant increase in lymphoproliferative responses for HPV 16 E4, E6, and E7 peptides (P=0.020, 0.020, 0.043). There was a significant association between change in lymphoproliferative response to HPV 16 E6 peptides and number of cycles of treatment administered (P=0.048). There was no correlation between change in lymphoproliferative response to any peptide with age, performance status, race, prior chemotherapy, time from diagnosis to treatment, or with overall survival. CONCLUSIONS: IL-12 treatment was associated with improved lymphoproliferative responses to HPV 16 E4, E6, and E7 peptides. This is the first clinical trial to demonstrate induction of cell-mediated immune (CMI) responses to specific antigens (peptides) following treatment with IL-12 in women with cervical cancer. This improvement in immune response was not associated with enhanced objective response or survival.     

Influence of Sources of Information and Parental Attitudes on Human Papillomavirus Vaccine Uptake among Adolescents

Study ObjectiveThe purpose of this study was to: 1) describe parental sources of information about human papillomavirus (HPV) vaccination for adolescents, 2) understand how parental sources of information about HPV vaccine are associated with adolescent HPV vaccine uptake, and 3) understand if the relationship between a greater number of HPV-related information sources and HPV vaccine uptake among adolescents is mediated by parental attitudes.Design, Setting, Participants, and InterventionsWe conducted a 3-arm randomized controlled trial in middle and high schools in eastern Georgia from 2011 to 2013. As part of the trial, we surveyed parents during the final year to understand their sources of information about HPV vaccine for their adolescent. Data were collected from 360 parents via phone and online surveys.Main Outcome MeasuresParents responded to a survey that asked them to identify demographic information, parental HPV attitudes, sources of information about HPV vaccination, and HPV vaccine uptake.ResultsMost of the sample was African American (74%; n = 267) and 53% of parents (n = 192) reported that their adolescent received at least 1 HPV vaccine dose. The top sources of information about HPV vaccine reported by parents were a doctor or medical professional (80%; n = 287) and television (64%; n = 232). A mediation analysis showed sources of information about HPV vaccine are associated with parental attitudes, and parental attitudes about HPV vaccine are associated with vaccine uptake among adolescents.ConclusionThese findings highlight the importance of HPV sources of information on parental attitudes.     

Prevalence of Human Papillomavirus in endometrial cancer: A systematic review and meta-analysis

Objective

HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer.

Methods

We conducted a systematic review and meta-analysis to investigate the pooled prevalence of HPV DNA in endometrial cancer. Using meta-regression, we further analyzed whether factors such as geographical region, HPV DNA detection method, publication year and tissue type were associated with HPV prevalence. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for studies providing data on HPV prevalence in cases with endometrial cancer and in controls with normal or hyperplastic endometrial tissue.

Results

We identified 28 papers (29 studies) examining the prevalence of HPV DNA in tumor tissue from endometrial cancer comprising altogether 1026 cases of endometrial cancer. The HPV prevalence varied considerably from 0% to 61.1%. From the random effects meta-analysis, the pooled prevalence of HPV DNA in endometrial cancer was 10.0% (95% CI: 5.2–16.2) with large between-study heterogeneity (I² = 88.2%, p < 0.0001). The meta-regression showed that HPV DNA detection method was statistically significantly associated with HPV prevalence (p = 0.0016): the pooled HPV prevalence was 6.0% (95% CI: 1.5–13.0) using general primers, 18.9% (95% CI: 8.6–32.1) using type-specific primers and 1.0% (95% CI: 0.0–3.6) using non-PCR based methods. None of the other a priori defined variables were statistically significantly associated with HPV prevalence. The pooled OR was 1.43 (95% CI: 0.68–3.00) indicating that the odds of HPV was not increased in cases versus controls.

Conclusions

HPV appears to have a limited or no role in the etiology of endometrial cancer.