Association between high risk human papillomavirus infection and co-infection with Candida spp. and Trichomonas vaginalis in women with cervical premalignant and malignant lesions

BackgroundHuman papillomavirus (HPV) is the necessary cause of cervical cancer. Cervico-vaginal infection with pathogens like Chlamydia is a likely cofactor. The interactions between HPV, Trichomonas vaginalis (TV) and Candida spp. are less understood, though inflammation induced by these pathogens has been demonstrated to facilitate oncogenesis.ObjectiveOur study aimed to evaluate the association between Candida spp. and TV co-infection with HPV in cervical oncogenesis.Study designWomen with normal cervix who were high-risk HPV-negative (N = 104) and HPV-positive (N = 105); women with CIN 1 (N = 106) and CIN 2/CIN 3 (N = 62) were recruited from a community based cervical cancer screening program. Cervical cancer patients (N = 106) were recruited from a tertiary care oncology clinic. High-risk HPV was detected by Hybrid Capture II technique; Candida spp. and TV were detected by culturing the high vaginal swabs followed by microscopic examination in all. The disease status was established by histopathology in all the women.ResultHPV-positive women had significantly higher risk of having precursor lesions (of any grade) and cancer compared to HPV-negative women. Candida spp. or TV infection did not alter the risk of low grade or high grade lesions among HPV- positive women. HPV positive women co-infected with TV had higher risk of cervical cancer but not those co-infected with Candida spp.ConclusionThe higher risk of cancer observed in the women co-infected with HPV and TV without any enhanced risk of CIN 3 suggests secondary infection of the malignant growth by TV rather than any causal role. Co-infection with Candida spp. and/or TV infection did not increase the carcinogenic effect of HPV on cervix.     

Human papillomavirus: molecular and cytologic/histologic aspects related to cervical intraepithelial neoplasia and carcinoma

Cervical cancer is unique among human cancers because it was the first cancer discovered to be virtually solely attributable to the effects of an infectious agent. Numerous epidemiologic and laboratory studies have confirmed a strong causal association between human papillomavirus infection and the development of premalignant and malignant lesions of the uterine cervix, and human papillomavirus-mediated malignant transformation is an ideal model system for the study of virally mediated carcinogenesis. Neoplastic transformation of affected cervical epithelium appears to be a direct consequence of the unregulated overexpression of viral oncoproteins that have central roles in the normal viral replicative cycle. This review is focused on the mechanisms that regulate the normal papillomavirus life cycle and on the mechanisms that appear to have central roles in malignant transformation of the cervical mucosa.     

134例宫颈上皮内瘤变患者HPV分型检测结果分析

目的探讨宫颈上皮内瘤变(CIN)中不同类型人乳头瘤病毒(HPV)的感染及分型情况。方法回顾性研究北京军区总医院妇科门诊134例已经确诊的CIN患者,采用凯普的核酸分子快速导流杂交基因芯片技术对HPV进行分型。结果 1.各级别CIN以HPV高危亚型单一或者多重感染为主;2.在HPV阳性的101例患者中,单一感染者73例(72.28%),双重感染者24例(23.76%),三重感染者3例(2.97%),四重感染者1例(0.99%);3.HPV-16、58感染率最高,分别为30.83%,24.06%。结论 HPV感染以高危型和多重感染为主;随CIN级别的增高,HPV阳性率也是增高的;HPV-16亚型的感染率最高。     

宫颈瘤变程度与其相对应的HPV基因型分布规律的研究

目的研究不同级别宫颈上皮内瘤变（cervical intraepithelial neoplasia,CIN）与人乳头瘤病毒（Human papil-lomavirus,HPV）基因型分布之间的关系。方法收集321例经组织病理学诊断确定为CIN2及以上（CIN2＋）病人的宫颈分泌物标本,其中CIN2 67例,CIN3/ACIS 247例,浸润性宫颈癌7例。采用深圳亚能生物技术有限公司的人乳头瘤病毒（HPV）基因分型检测试剂盒对所选标本进行HPV检测及基因分型。结果在所有321例标本中,HPV阳性300例,阳性率93.5%,两型及两型以上感染138例,占比43.0%。HPV16最常见,检出率为41.1%（132/321）,其次为HPV31,33,52,18和51。HPV16和33的单型感染在CIN3＋中比CIN2更常见,具有统计学差异（P〈0.05）。在包含有HPV16或HPV33的多型感染中,含有HPV16或HPV33的多型感染在CIN3＋中比CIN2更常见,具有统计学意义（P〈0.05）。结论 HPV16和HPV33比其他型别HPV具有更强的潜在致癌性。     

Assessing oral brushing technique as a source to collect DNA and its use in detecting human papillomavirus

Collecting buccal cell DNA has a number of advantages in terms of practicality and technical quality when employed for detecting human papillomavirus (HPV), arguably an important etiological factor for head and neck carcinomas. The objective of the present study was to assess oropharyngeal mucosa brushing as an effective method for collecting DNA samples and for detecting HPV. Forty-three female patients diagnosed with cervical intraepithelial neoplasia, and 21 of their spouses, both groups without clinically detectable oral lesions, were submitted to quantitative and qualitative DNA analysis obtained through buccal cell brushing, with spectrophotometry assessment and beta-globin PCR. DNA samples were also checked for the presence of HPV. Efficient collection of DNA was achieved in all the sample cases. Two samples, a male and a female (not sexual partners), showed HPV-positivity. The results revealed that the oral brushing technique is an effective method for DNA collection to detect HPV, confirming that it could usefully contribute to epidemiological studies undertaken in Brazil's Public Health System. HPV detection using PCR showed that only 3.12% of the cases were HPV-positive. Although the sample was small, our study nevertheless allowed the detection of HPV in DNA samples of oral biological material.     

Cytologic indicators of condylomatous lesions of the uterine cervix with histologic correlation: an outpatient laboratory's experience

Human papillomavirus (HPV) is widely implicated as a primary etiologic factor in cervical carcinoma. Cytology plays an important role as the initial screening tool in the early detection of cervical lesions with koilocytotic features. The purpose of this study was to describe the various cytologic indicators of condylomatous lesions of the uterine cervix with histologic correlation. Cervical smears and biopsy specimens from 278 women seen in an outpatient clinical setting between January 1, 1985; and January 1, 1987, were reviewed. The histologic categories consisted of (1) flat condylomas with minimal cellular atypia; and (2) cervical intraepithelial neoplasia (CIN), I, II, or III with atypical koilocytosis. Cytologically in 57 cases, flat condylomas were composed predominantly of koilocytes containing large perinuclear halos and dyskeratotic cells. In the 221 cases of CIN with atypical koilocytosis, the cervical smears were composed predominantly of atypical koilocytes with large hyperchromatic nuclei and small perinuclear halos; a variable number of koilocytes with large perinuclear halos; pleomorphic dyskeratotic cells; and abnormal multinucleated cells. Mild, moderate, or severely dysplastic/carcinoma-in-situ cells (CIS) were also present. An understanding of the cytologic features associated with condylomatous lesions of the cervix will enable the cytopathologist to alert the clinician of the need to perform colposcopy with the appropriate follow-up treatment.     

15 393例宫颈液基细胞学与组织病理学的对照分析

目的探讨宫颈液基细胞学诊断与组织病理学诊断的符合情况。方法对15393例做SurePath宫颈液基细胞学检查,结果异常者依次做Hybrid Capture-Ⅱ肿瘤相关人乳头状瘤病毒（HPV）-DNA检测、5％醋酸宫颈染色肉眼观察并拍照、阴道镜检查及宫颈多点活检行组织病理学检查。细胞学诊断采用TBS（2001）分级报告系统,阳性诊断包括意义不明的不典型鳞状细胞（ASC-US）以上病变;本组细胞学阳性病例有组织病理诊断结果,并对两者进行了对照分析。结果15393例宫颈细胞学检查与组织病理学对照结果显示：7例鳞状细胞癌（SCC）均符合,高级别鳞状上皮内病变（HSIL）为93．6％（103／110）、低级别鳞状上皮内病变（LSIL）为82．0％（443／540）。HPV—DAN阳性检出率与细胞学TBS分级及组织病理学分级正相关。结论应用液基细胞学制片方法、准确掌握TBS的诊断标准可确保宫颈细胞学检查的准确性。     

The performance of human papillomavirus DNA detection with type 16/18 genotyping by hybrid capture in primary test of cervical cancer screening: a cross-sectional study in 10,669 Chinese women

ObjectivesWe aimed to assess the performance of DH3 human papillomavirus (HPV) assay, a newly developed hybrid capture technique that detects 14 high-risk HPVs with type 16/18 genotyping, as a primary test in cervical cancer screening.MethodsIn total 11,356 Chinese women aged 21–65 years participated in a cervical cancer screening programme using cytology (Thinprep, Hologic) and HPV testing (Cobas 4800 Test, Roche). Residual samples were used to detect HPV by DH3 HPV.ResultsIn total 10,669 women with valid results were included in the study. Of those, 135 were diagnosed as CIN2+, and 83 were diagnosed as CIN3+; 1056 women (9.9%) were DH3 HPV-positive and 255 (2.4%) of those were 16/18-positive, while 990 (9.3%) women were Cobas HPV-positive and 243 (2.3%) of those were 16/18-positive. DH3 HPV was non-inferior to Cobas HPV in identifying CIN1− and CIN2+ using predetermined thresholds (both p < 0.001). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of DH3 HPV were 93.3% (95% confidence interval [CI] = 87.7–96.9), 91.2% (95%CI = 90.6–91.7), 12.0% (95%CI = 10.1–14.1) and 99.9% (95%CI = 99.8–100), respectively, similar to those of Cobas HPV (91.1%, 95%CI = 85.0–5.3; 91.8%, 95%CI = 91.2–92.3; 12.5%, 95%CI = 10.5–14.7; and 99.9%, 95%CI = 99.8–99.9, respectively), in identifying CIN2+ (all p > 0.05). When DH3 HPV and Cobas HPV were respectively used as primary testing in screening strategy, the performance of two strategies were similar in identifying CIN2+. The results were similar in identifying CIN3+.ConclusionOur data suggest that DH3 HPV performs similarly to Cobas HPV in identifying high-grade CIN in cervical cancer screening.     

The human papillomavirus (HPV) vaccine,HPV related diseases and cervical cancer in the post-reproductive years

Prophylactic HPV vaccines have demonstrated high efficacy against a range of HPV related diseases. They have been widely adopted as population health interventions in many jurisdictions and their routine use has been endorsed by the WHO. The development of these vaccines comes after an increased understanding of the natural history and epidemiology of HPV infection and disease in both males and females. Persistent HPV infection with oncogenic types induces malignant transformation in a range of epithelia including the cervix, anogenital regions, the penis and a number of head and neck sites. In relation to HPV disease prevention in the post-reproductive years, most infections occur soon after commencement of sexual activity but new infections do occur throughout the age spectrum. This reduces the likely impact of prophylactic vaccines in this population. The major impact on HPV related disease in this age group will come from advances in screening and early detection of HPV and neoplastic precursors. The most appropriate prevention for any individual man or women in this age group will be an individualised combination of vaccination, screening and early detection depending on the individual's own circumstances.     

Detection of human papillomavirus (HPV) genotypes in cervico-vaginal scrapes of women with normal and abnormal cytology

Background   Certain types of human papillomavirus (HPV) are associated with cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The study addressed the expression and detection of HPV genotypes in cervical and vaginal specimens of women with normal and abnormal cytology by polymerase chain reaction (PCR), each woman serving as her own control.
Methods   Study participants (127) were subgrouped into CIN-positive and CIN-negative, based on cytology screening, and endocervical and vaginal scrapes were collected by a gynecologist and placed immediately in saline. HPV DNA was assessed by PCR, and HPV genotypes were determined by hybridization of PCR products with type-specific biotinylated probes.
Results   Of the 127 participants, 55 tested positive and 72 tested negative for HPV DNA. While there was no difference between the two groups with regards to age or to number of pregnancies, higher numbers of smokers and of women with multiple sexual partners and abnormal cytology were seen in the HPV-positive group ( P  < 0.001). HPV DNA was detected in the vaginal scrapes of all HPV-positive, but in none of the HPV-negative women (sensitivity and specificity = 1.0). Furthermore, the HPV genotype was the same in vaginal and endocervical specimens in all the HPV-positive women.
Conclusion   HPV detection by PCR, using endocervical or vaginal sampling, is a sensitive and highly specific test for the identification of HPV infection, in particular in women with cytomorphologically normal cervices.     

宫颈癌及其前期病变HPV感染与基因型分布

目的了解宫颈癌及宫颈上皮内瘤变CIN患者的HPV的感染和其基因分型及主要感染型别情况。方法应用型特异PCR检测宫颈癌及其前病变的患者的HPV感染及其主要基因分型情况的分析。结果在本研究宫颈癌及宫颈上皮内瘤变患者中,宫颈癌的HPV感染率为91．0％,CINⅠ／Ⅱ／Ⅲ的HPV感染率为73．3％,主要高危型HPV基因型别依次为HPV16、HPV18、HPV58、HPV33。结论在宫颈上皮内瘤变患者中感染主要高危型HPV基因型别依次为HPV16、HPV18、HPV58、HPV33、HPV16在宫颈癌和CIN中的构成比随着宫颈病变的增加而明显增加。     

Detection of human papillomavirus in sanitary napkins: a new paradigm in cervical cancer screening

Human papillomavirus was successfully detected by polymerase chain reaction (PCR) in menstrual blood or vaginal discharge collected in sanitary napkins in 100% of 17 women having koilocytosis, cervical intraepithelial neoplasia, or squamous carcinoma. We advocate this form of cervical cancer screening because of its high sensitivity and acceptance by patients.     

Detection and typing of human papillomavirus DNA in the uterine cervix of japanese women by nonradioactive dot blot and southern blot hybridization

HPV infection was examined with Cytobrush in exfoliated cervical cells sampled from 347 women. HPV DNA analysis was conducted in two steps. The presence of HPV DNA was demonstrated by dot blotting and typing of HPV DNA was made by Southern blotting using biotinylated probes. Of 167 cases with cervical intra-epithelial neoplasia (CIN) and cervical carcinoma, HPV DNA was detected and typed in 25 cases (15.0%). HPV 16, 18, and 33 were found mainly, and no HPV 6 or 11 was detected. The frequency of HPV DNA was 7.1% of CIN I, 28.6% of CIN II, 54.5% of CIN III, and 50.0% of invasive carcinoma. HPV occurred in patients newly diagnosed as CIN at 25.8% and in those of diagnosed as CIN in the past and followed up, 7.6%. Of 180 healthy women, the screening test of F08830 was positive for HPV DNA in four women (2.2%). The present system proved to be useful for facilitating large-scale clinical research.     

安阳市宫颈病变患者人乳头瘤病毒感染现状及基因分型分析

目的:分析安阳市宫颈病变患者人乳头瘤病毒（human papillomavirus,HPV）感染现状,并分析其基因型。方法:选取2018年6月至2020年12月在本院门诊就诊或住院治疗的宫颈病变患者372例,参照宫颈组织病理活检结果分为宫颈炎、宫颈上皮内瘤变（cervical intraepithelial neopl...     

Direct comparison of two vaginal self-sampling devices for the detection of human papillomavirus infections

Background and objectivesTwo devices for vaginal self-sampling of dry cell material (Evalyn Brush, Rovers Medical Devices; Qvintip, Aprovix) were compared using the Abbott RealTime High Risk HPV test.Study designBoth self-sampling devices (change of order with every patient) including instructions for use and a questionnaire were handed to 146 patients in a colposcopy clinic prior to scheduled colposcopies with collection of cervical reference specimens by gynaecologists using a broom-like device. Matched self-collected and physician collected specimens were transferred to ThinPrep medium and tested for the presence of hr-HPV. Biopsies were taken if indicated by colposcopy.ResultsEvaluation of 136 patients with complete data (136/146; 93.2%) showed high agreement of overall hr-HPV detection rates between self-collected and clinician-collected specimens (Evalyn: 91.2% [kappa 0.822]; Qvintip: 89.0% [kappa 0.779]). Colposcopy and histological evaluation revealed 55 women without cervical intraepithelial neoplasia (CIN), 32 CIN1, 34 CIN2, 14 CIN3 and one adenocarcinoma in situ. Hr-HPV testing detected all CIN3+ cases on the clinician-taken or Evalyn self-samples (14/14) and 93% of them on the Qvintip samples (13/14). There was no significant difference regarding the sensitivity for CIN2+ or CIN3+ and specificity of hr-HPV testing on self- vs. clinician samples and on Evalyn vs. Qvintip. Based on signal intensities of β-globin, the observed DNA concentration with Evalyn samples (mean CN: 22.0; 95%-CI: 21.5–22.6) was found to be significantly higher compared to that of Qvintip samples (mean CN: 23.8; 95%-CI 23.2–24.4), regardless of the order of self-sampling (p < 0.0001). Most women considered self-sampling easy and comfortable. Qvintip was considered easier than the Evalyn Brush to understand (p < 0.001) and to use (p = 0.002).DiscussionThis study confirms that hr-HPV testing with a clinically validated PCR-based HPV assay is as accurate on self-samples as on clinician-samples without significant difference between both self-sampling devices.     

Association of human papillomavirus type 16 and its genetic variants with cervical lesion in Korea

Persistent human papillomavirus type 16 (HPV16) is the major risk factor for cervical cancer. HPV16 intratypic variants differ in their geographical distribution and oncogenic potential. This study aimed to analyze the distribution of HPV16 variants and their association with cervical lesion histopathology in Korean women. In total, 133 HPV16‐positive cervical samples from women admitted to Seoul National University Boramae Hospital were analyzed by sequencing E6, E7, and L1 genes and the long control region (LCR), and the variant distribution according to cervical lesion grade was determined. Isolates were grouped into a phylogenetic lineage, and A1‐3, A4, C, and D sublineages were detected in 54.1, 37.8, 0.7, and 7.4% of samples, respectively. The most commonly observed LCR variations were 7521G>A (91.5%), 7730A>C (59.6%), and 7842G>A (59.6%). Furthermore, A4 or D sublineage‐positive women had a higher risk for cervical cancer than women who were positive for A1–3. Among HPV phylogenetic clusters, A1–3 was the predominant sublineage, and within A1–3, the 350G polymorphism was highly frequent. These results differed from those of previous studies in Korea and other Asian countries. The findings suggest that cervical neoplasia incidence in HPV16‐infected patients could be affected by the distribution of HPV16 variants in the population.     

Human papillomavirus genotyping as a predictor of high-grade cervical dysplasia in women with mildly cytologic abnormalities: a two-year follow-up report

High-risk human papillomavirus (HR-HPV) DNA testing has emerged as another testing modality for women with mildly cytologic abnormalities. We conducted a two-year follow-up study of 108 women with mildly abnormal cervical cytology for detection of CIN 2/3. A cervical swab sample was obtained for HPV genotyping by a HPV blot and histologic follow-up results were correlated with HR-HPV types. Of the 108 cases, 93 (86.1%) were positive for HR-HPV DNA. HPV-16 was detected in 45.1% of patients. CIN grade 2 or 3 was confirmed in 25 (23.1%) of the 108 women during the two-year follow-up period. The two-year cumulative incidence rates of CIN 2/3 were 38.6% (17/44) among HPV-16- positive women, but only 5.6% among HR-HPV-positive women without HPV-16 or HPV-18. The sensitivity of a positive HPV-16 test for CIN 2/3 was 68.0%, the specificity was 67.5%. Our results demonstrated that the type-specific HPV-16 test increased sensitivity of detecting high-grade cervical dysplasia for women who have mildly cytologic abnormalities. The implication of the present findings is that HPV genotyping may identify women with the greatest risk of high-grade CIN.