Identification of vaccine human papillomavirus genotypes in squamous intraepithelial lesions (CIN2-3)

ObjectiveTo identify the prevalence of human papillomavirus vaccine genotypes and non-vaccine genotypes implicated in the appearance of cervical intraepithelial neoplasia (CIN2–3).MethodsProspective study of 519 women with abnormal cytology. All the women underwent a second Papanicolaou test, cervicovaginal sampling for type-specific HPV detection and colposcopy, and women with abnormal colposcopy results were referred to biopsy. Pearson's chi-square test was used for statistical analysis.ResultsHPV was detected in 340 patients (65.5%), and in 125 (24%) more than one HPV genotype was present. We selected 206 patients with CIN2 or CIN3 confirmed by biopsy. In 88 (42.7%) of these patients, HPV types 16 and 18 were detected, but only 58 (28.2%) without co-infection by other high-risk or probable high-risk HPV types. In 115 (55.8%) women diagnosed with CIN2 or CIN3 high-risk or probable high-risk HPV types other than 16 or 18 were found. High-risk and/or probable high-risk HPV genotypes not included in the vaccine were isolated in this study more frequently than 16 or 18, and this difference was statistically significant (p = 0.047). Of the 206 women diagnosed with CIN2 or CIN3, 19 tested negative for HPV and 14 tested positive for low-risk HPV types.ConclusionOnly 28.2% of women with CIN2 or CIN3 confirmed by biopsy were infected exclusively by HPV type 16 or 18, a finding that places in doubt the degree of protection afforded by HPV vaccination.     

High-risk human papillomavirus,other than type 16/18, in predominantly older Taiwanese women with high-grade cervical preinvasive lesions

ObjectiveTo investigate the various genotypes of human papillomavirus (HPV) in Taiwanese women patients with abnormal cervical cytology and analyze the associations between HPV types, cervical preinvasive lesions, and the medical characteristics of these patients.Materials and MethodsWe performed HPV genotyping GeneChip procedures and colposcopies for 784 women with abnormal Papanicolaou smears. The characteristics of the patients and the status of the HPV infection were correlated.ResultsA total of 706 (90.1%) of the 784 women were positive for HPV infection, including 641 patients with high-risk HPV (HR-HPV). Among the patients with high-grade squamous intraepithelial lesions (HSILs), the average age of the 273 patients with other HR-HPV types (48.6 ± 13.8 years) was significantly older than the 222 patients infected with HPV 16/18 (39.8 ± 11.8 years) (p < 0.001). The proportion of patients with HSILs who were older than 40 years and infected with other HR-HPV types (76.6%) was also significantly higher than those with HPV 16/18 (20.3%) (p < 0.001).ConclusionWomen older than 40 years and having abnormal Pap smears and HR-HPV infections other than type 16/18 should be managed carefully because of the risk for HSILs.     

Incidence of cervical intraepithelial neoplasia in a cohort of HIV-infected women

ObjectiveTo assess cervical intraepithelial neoplasia (CIN) incidence in HIV-positive women and the risk factors for these lesions.MethodsA retrospective and longitudinal cohort study was conducted from June 13, 1997, to December 18, 2009. At the first visit, the 348 participants had a normal cytologic finding but a negative Schiller test result, or an abnormal cytologic finding but no histologic diagnosis of CIN. Infection with HPV was detected by polymerase chain reaction. The main outcome measure was CIN incidence.ResultsDuring a mean follow-up of 40 months, 47 women (13.5%) developed CIN, for an incidence of 4.1 cases per 100 person-years of follow-up. The HPV prevalence was 68.1%, 42 women (89.4%) developed CIN 1, and no invasive cervical cancers were identified. On multivariate analysis, women younger than 19 years at first sexual intercourse (RR, 2.6; 95% CI, 1.24–5.35) and women who had never used antiretrovirals or used them only during pregnancy (RR, 2.3; 95% CI, 1.31–4.19) were at higher risk for CIN.ConclusionThe CIN incidence was low despite the high HPV prevalence. Being younger than 19 years at first sexual intercourse and not using antiretroviral medications were found to be the main risk factors for CIN.     

Prognostic value of pre-treatment human papilloma virus DNA status in cervical cancer

Objective

Although the relationship between human papilloma virus (HPV) and cervical cancer is well established, the prognostic value of HPV status has not been determined, largely because previous studies have yielded conflicting results. This study aimed to investigate the prognostic value of pre-treatment HPV DNA for predicting tumor recurrence in cervical cancer.

Prévalence des génotypes d’HPV chez les femmes en France : implications pour le dépistage et la vaccination

ObjectivesTo assess human papillomavirus (HPV) prevalence and genotype distribution by age and cervical cytology/histology status among women undergoing routine gynecological examinations, and to discuss the possible impact on preventive strategies.Patients and methodsLiquid-based cytology (LBC) samples were tested for HPV DNA, mRNA, and HPV genotypes. Women with ASC-US+ and/or at least one positive HPV test were referred to colposcopy. Those with normal colposcopy results had biopsies taken at the 6 and 12 o’clock positions of the normal transformation zone.ResultsOf the 5002 women, 515 (10.3 %) were less than 25 and 4487 (89.7 %) were 25 years old or more. Overall HPV prevalence was 10.1 % to 16.1 % depending on the assay. HPV prevalence increased with the cytological and histological severity of cervical lesions. Prevalence of HPV 16/18 was 5.2 % and 2.7 % in women less than 25 and 25 years old or more, respectively. HPV 16 was the type most strongly associated with a diagnosis of CIN3+ (odds ratio = 11.64 versus HPV 16 absent, P < 0.001). A high proportion of high-grade cervical lesions (60.6 % of genotyping assay-positive CIN2+) were associated with HPV types 31, 33, 45, 52, or 58.Discussion et conclusionThese data indicate that almost all young women could benefit from HPV prophylactic vaccination, but confirm the need for continued cervical screening and highlight the need for future vaccines to target a wider range of HPV types.     

A systematic review and meta-analysis on the attribution of human papillomavirus (HPV) in neuroendocrine cancers of the cervix

Background

There remains uncertainty about the role of human papillomavirus (HPV) infection in causing small-cell neuroendocrine carcinoma (SCNC) and large-cell neuroendocrine carcinoma (LCNC) of the cervix. To clarify the role of HPV in the development of SCNC and LCNC, we conducted a systematic review and meta-analyses.

Detection of human papillomavirus genotypes associated with mucopurulent cervicitis and cervical cancer in Changchun,China

ObjectiveTo determine the prevalence and genotype distribution of human papillomavirus (HPV) infection among Chinese patients with mucopurulent cervicitis (MPC) or cervical cancer (CC).MethodsIn total, 191 cases of CC (n = 66), acute MPC (n = 84), and healthy cervix controls (n = 41) were initially included; samples were collected between May 21, 2008, and October 9, 2011. Cervical specimens were screened for HPV using a nested polymerase chain reaction assay and DNA sequencing.ResultsOverall prevalence of HPV infection was 20.0% in the control group, 53.3% in the MPC group, and 93.8% in the CC group. The predominant genotype detected in all 3 groups was the oncogenic variant HPV 16 (87.7%, 18.7%, and 10.0% in the CC, MPC and control specimens, respectively). The second most frequent genotype among patients with MPC was HPV 58. This variant is also oncogenic and was detected at a higher rate in the MPC group (9.3%) than in the control (2.5%) and CC (1.5%) groups.ConclusionInfection with HPV was prevalent among Chinese women with MPC or CC. Furthermore, the high prevalence of oncogenic genotypes observed among HPV-positive patients with MPC suggests that this group is at increased risk of developing CC.     

Impact of HPV 16/18 infection on clinical outcomes in locally advanced cervical cancers treated with radical radio (chemo) therapy - A prospective observational study

Objective

With an aim to investigate the impact of Human Papilloma Virus (HPV) 16/18 infection on clinical outcomes in locally advanced cervical cancers treated with radical radio (chemo) therapy, we undertook this prospective study.

Racial/ethnic differences in HPV 16/18 genotypes and integration status among women with a history of cytological abnormalities

Objective

HPV genotype distribution varies by race/ethnicity, but is unclear whether there are racial/ethnic variations in HPV 16/18 integration in the host genome. We describe HPV16/18 infection and integration status in a racially/ethnically diverse sample of women with a recent abnormal Pap test.

Hospital-based prevalence of high-risk cervical HPV types infecting the general population and female sex workers in Huzhou,China

ObjectiveTo evaluate the prevalence of high-risk HPV types among female sex workers and the general population in Huzhou, China.MethodsCervical samples from the general population (n = 292) and female sex workers (n = 288) in Huzhou, China, were collected between April, 2008, and October, 2009. Demographic, behavioral, and clinical data were obtained by interview. Genotyping of the HPV L1 gene was done via a PGMY09/PGMY11 PCR-based assay, and the cervical samples were subjected to cytology analysis.ResultsThe prevalence of HPV was higher among female sex workers (66.7%) than among the general population (19.2%). Among female sex workers, HPV-16 (28.8%) was the most prevalent, followed by HPV-58 (24.0%) and HPV-52 (20.8%). The percentage of cervical abnormalities was higher among female sex workers (20.8%) than among the general population (4.8%). Multivariate analysis showed that education level and condom use during coitus were significantly associated with HPV infection (P < 0.05). HPV-16, HPV-58 and HPV-52 were the dominant types, and were significantly associated with abnormal cervical cytology (P < 0.05).ConclusionFemale sex workers in Huzhou, China, were found to have a greater probability of being infected with high-risk HPV, and novel vaccines against HPV-58 and HPV-52 should be developed. Using condoms could reduce the risk of infection.     

Triaging HPV-positive women with p16/Ki-67 dual-stained cytology: Results from a sub-study nested into the ATHENA trial

Objectives

In addition to genotyping for HPV16/18, dual-immunostaining for p16/Ki-67 has shown promise as a triage of HPV-positive women. We assessed the performance of p16/Ki-67 dual-stained cytology for triaging HPV-positive women undergoing primary HPV screening.

Dysplasies cervicales chez les femmes séropositives pour le VIH en zone de forte prévalence de l’infection

ObjectivesTo determine the prevalence of cervical squamous intraepithelial lesions among HIV-positive women, compared to that of HIV-negative women and identify the different types of lesions in both groups.Patients and methodsCross-sectional study conducted in 16 months in two facilities and the service of pathological anatomy of Bangui. The sample consisted of 250 HIV-positive women matched to 250 HIV-negative women. The parameters studied were the HIV status, the result of cervical smear screening, the rates of CD4 and the data of the interview.ResultsThe smears were inflammatory in 54.4% of HIV-negative and 46.4% of HIV-positive. Epidermoid intraepithelial lesions of the cervix were more frequent among HIV-positive women than among HIV-negative women with respectively 34.8% and 16.4% (P < 0.0001). The low-grade lesions were more common regardless of HIV status of patients. The median age of onset of the LEI was lower among HIV-positive whatever the grade of the lesion. Koïlocytosis was found in 27.2% of HIV-positive women against 9.2% among HIV-negative (P <0.001).Discussion and conclusionThe prevention of infection by HIV and HPV and the monitoring of precancerous lesions would allow to prevent their evolution towards invasive cancer.     

The landscape of somatic mutations in Indonesian cervical cancer is predominated by the PI3K pathway

Objective

To investigate the prevalence of somatic mutations in Indonesian cervical carcinoma patients in the context of histology and human papillomavirus (HPV) type.

Human papillomavirus viral load as a useful triage tool for non-16/18 high-risk human papillomavirus positive women: A prospective screening cohort study

Objective

ASCCP cervical cancer screening guidelines recommend triaging high-risk human papillomavirus (hrHPV) positive women with cytology and genotyping, but cytology is often unavailable in resource-limited areas. We compared the long-term risk of cervical cancer and precancers among type-specific hrHPV-positive women triaged by viral load to cytology and visual inspection with acetic acid (VIA).

Downregulation of tumor suppressor gene PML in uterine cervical carcinogenesis: Impact of human papillomavirus infection (HPV)

ObjectivesCervical cancer is a leading gynecological cancer in Indian women and is caused due to infection with high risk human pappilloma virus (HR-HPV) 16 and 18. It has been well documented that PML (promyelocytic leukemia) enhances viral infectivity and plays a crucial role in antiviral response mechanisms. The aim of the present study was to evaluate the role of PML gene with context to HPV infection in cervical carcinogenesis.MethodsThe expression pattern of PML was analyzed by western blotting and immunohistochemistry in a total of 170 fresh surgically resected cervical tissue specimens comprising precancer (n = 12), cancer (n = 118) and normal controls (n = 40) recruited from PGIMER, Chandigarh, India. HPV status was analyzed by L1 consensus PCR followed by type specific PCR for HR-HPV types 16 and 18 and low risk types 6 and 11.ResultsA significant downregulation of PML protein was observed in the majority of cervical cancer and precancer cases 68% (89/130) compared to normal controls. The loss of expression pattern of PML gene was significantly increased with severity of disease both clinically and pathologically (p < 0.001). HPV infection was detected in the majority of cancer cases 96% (113/118) and in 83% (10/12) of precancer lesions whereas no infection could be detected in normal controls. Interestingly, all the 68% (89/130) cervical cancer cases that showed downregulation of PML were HPV infected (p = 0.0001).ConclusionTaken together, these observations suggest that the downregulation of PML gene and its synergism with HPV infection may play an important role and may serve as a new marker for early diagnosis and therapeutic intervention for cervical carcinogenesis.     

22234例子宫颈高危型HPV感染及亚型分布研究

目的:分析17种型别的高危型人乳头瘤病毒(HPV)在22234例子宫颈癌筛查中的感染率及亚型分布特点。方法:回顾性分析2018年1月1日至2019年1月1日22234例于华中科技大学同济医学院附属协和医院行子宫颈癌筛查患者高危型HPV感染率及感染亚型。结果:22234例接受子宫颈癌筛查患者中,一种或以上高危型HPV阳性者3574例(16.1%),其中HPV16或(和)HPV18阳性者703例(3.2%)。在3574例高危型HPV阳性女性中,最常见的高危HPV感染是HPV52(24.4%),其次为HPV58(16.5%)、HPV16(14.0%)、HPV53(12.6%)和HPV39(8.6%)。与HPV16阴性患者相比,在HPV16阳性的患者中,除HPV31、HPV35、HPV45、HPV26和HPV82以外的12种高危型HPV的感染风险均显著降低约2～5倍((印)OR(正) 0.169～0.530,(印)P(正)<0.05);与HPV18阴性患者相比,HPV18阳性的患者中HPV16、HPV33、HPV39、HPV51、HPV52、HPV58和HPV53的感染风险均显著下降((...     

Telomere length in leukocytes and cervical smears of women with high-risk human papillomavirus (HR HPV) infection

ObjectivePersistent high-risk HPV (HR HPV) infection leads to the development of squamous intraepithelial lesions, which in turn may progress to cervical cancer. Telomere elongation or shortening may indicate a carcinogenesis process. In the present study, we analyzed telomere length from blood and cervical smears of women without and with high-risk HPV infection.Materials and methodsTelomere length was quantified by real-time PCR in blood and cervical smears from 48 women with high-risk HPV infection and HGSIL or LGSIL, 29 women HR-HPV positive without SIL, and 11 HPV-negative women.ResultsNo correlation was found between age and telomere length in blood and cervical smears. Women with high-risk HPV infection had shorter telomeres in cervical smears, but not in blood compared to the control group.ConclusionThese findings suggest that telomere shortening occurs in cervical cells of women with HR HPV infection both with LGSIL and HGSIL and may indicate the onset of carcinogenesis. In turn, there is no correlation between leukocyte telomere length and cervical cancer risk in women with HR HPV infection.     

Comparison of three human papillomavirus DNA assays and one mRNA assay in women with abnormal cytology

ObjectiveTo compare the clinical characteristics of four human papillomavirus (HPV) assays: hybrid capture 2 (HC2), cobas, CLART, and APTIMA in Danish women with abnormal cytology.MethodsSurePath samples from 367 consecutive women from Copenhagen, with atypical squamous cells of undetermined significance or worse, were tested with the four assays. These women were routinely recommended for repeated testing or were referred for colposcopy. Their worst histological diagnosis in 29 months from baseline was retrieved from the Danish National Pathology Data Bank.ResultsOf the 367 women, 16 (4%) had no follow-up, 232 (63%) had < CIN2, 35 (10%) had CIN2, 81 (22%) had CIN3, and 3 (1%) had cervical cancer. The sensitivity for ≥ CIN3 was 95% (95% CI: 88–99) for HC2, 94% (95% CI: 87–98) for cobas, 93% (95% CI: 85–97) for CLART, and 87% (95% CI: 78–93) for APTIMA. In women of age above 30 years, the sensitivities were 98% (95% CI: 87–100), 93% (95% CI: 80–98), 90% (95% CI: 77–97), and 93% (95% CI: 80–98), respectively. One woman with cervical cancer tested negative on CLART and one on cobas; HC2 and APTIMA were positive in all three cancer cases. The specificity for < CIN3 was low for all assays and varied between 22% and 35%. Similar results were seen for ≥ CIN2.ConclusionsSmall differences in clinical characteristics were found for the four HPV assays in Danish women with abnormal cytology aged ≥ 30 years. At younger ages, APTIMA was somewhat less sensitive for high-grade CIN than the three HPV DNA assays.     

Pap Smear Knowledge Among Young Women Following the Introduction of the HPV Vaccine

Study ObjectiveInvestigate sexually active young women's knowledge of the term Pap smear since development of the HPV vaccine.DesignCross-sectional study conducted January–May 2007.SettingUniversity health services clinic at a university in southern United States.ParticipantsSexually active women, age 18–24, presenting for a Pap smear or STD testing (N = 145).Main Outcome MeasuresPap smear knowledge was assessed by participants' written definition of the term Pap smear and by multiple choice responses indicating Pap smear as a test for cervical cancer/ HPV and not a pelvic exam, STD test, or pregnancy test.Results9.7% provided accurate definitions; 12.4% checked appropriate Pap smear synonyms. 68.5% incorrectly responded that Pap smear was the same as “pelvic exam”; 42.5% indicated “STD test”; 11.7% indicated “pregnancy test.” Indicators of HPV risk (age of sexual debut, previous abnormal Pap smear, previous STD diagnosis) were not associated with knowledge. Never using condoms, increasing age, and lower depression scores predicted accurate Pap smear definition rating (R² = 0.08). Never using condoms, Caucasian race, and decreased lifetime number of sex partners predicted accurate identification of Pap smear synonyms (R² = 0.15).ResultsFew participants understood the meaning of the term Pap smear; there does not appear to be improvement in women's knowledge after development of the HPV vaccine. Poor Pap smear knowledge may affect young women's understanding of their overall sexual health.     

Is human papillomavirus genotype important in predicting disease progression in women with biopsy-proven negative or CIN1 of atypical squamous cell of undetermined significance (ASC-US) cytology?

Objectives

Our aim was to estimate the risk of disease incidence in women with atypical squamous cell of undetermined significance (ASC-US) without histology-proven cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) by human papillomavirus (HPV) genotype.