HPV16 is associated with younger age in women with cervical intraepithelial neoplasia grade 2 and 3

Objective

To evaluate if women with HPV16 positive CIN2 and CIN3 are diagnosed at a younger age.

Methods

We conducted a population-based cohort study including more than 40,000 women having a liquid based cervical cytology sample taken as part of routine screening. HPV analysis was performed using Hybrid Capture 2 and LiPAv2. The study population was linked to the Danish Pathology Data Bank to retrieve information on subsequent cervical histology. We included HR HPV positive CIN2/3 samples, comprising 173 CIN2 and 467 CIN3 lesions. Due to a high number of multiple concurrent HPV infections, the causative HPV type was assigned to a hierarchically group.

Results

In CIN3, the estimated proportion of lesions positive for HPV16 was 68.1% among women aged 20 years and decreased to 38.9% among women aged 50 years. A decrease in HPV16 positivity with increasing age was also observed in CIN2. In a multinomial logistic regression analysis, young age was strongly associated with HPV16 positivity in CIN3 lesions (OR = 0.46 per 10 year increase in age, 95% CI: 0.32-0.65). The proportion of HPV16 and/or 18 positive lesions among women diagnosed with CIN2 and CIN3 below 30 years of age was 44% and 75%, respectively.

Conclusions

HPV16 positivity was significantly associated with younger age at diagnosis of CIN3. In a population vaccinated against HPV16 and 18, we will experience a shift to older ages in cervical precancerous lesions. These findings may imply that cervical cancer screening programs could start at an older age in HPV vaccinated populations.     

Diagnosis of cervical intraepithelial neoplasia and human papillomavirus infection: punch biopsy versus cervical smear

Summary In 102 patients referred to our colposcopy clinic because of one to three Papanicolaou smears indicating cervical intraepithelial neoplasia (CIN) and/or abnormal colposcopy, routine smears and colposcopically directed punch biopsies were taken simultaneously. For detection and typing of human papillomavirus (HPV)-DNA in situ hybridization was performed in all biopsies and in 46 of the cervical smears. In cases of dysplastic lesions the number of HPV 16/18 (40.5%) and 31/33 (42.9%) was markedly higher than HPV 6/11 (16.6%) infection rate. In cases where simultaneous in situ hybridization in biopsy specimen and cervical smears was performed 21.7% showed a HPV negative smear and a positive biopsy, in 6.5% the results were the other way round. In 34.9% of cases with CIN I and 9.5% of cases with CIN II verified by punch biopsy the cytological smear did not indicate dysplasia. Our data show that mild and moderate CIN lesions of the cervix as well as HPV infection are detected more frequently by a combination of cervical smear and colposcopically directed punch biopsy than by cervical smear alone.     

Analysis of transforming gene regions of human papillomavirus type 16 in normal cervical smears

Summary Exfoliated cells from the uterine cervix of 102 Hungarian women with no cytological abnormality were screened using the polymerase chain reaction (PCR) for human papillomavirus (HPV) type 16 infection. Twenty-nine patients with histologically confirmed cervical intraepithelial neoplasia (CIN) served as reference cases. PCR was performed with 2 different HPV 16 specific oligonucleotide primer pairs flanking a 300 and a 200 base-pair fragment from the early 6 (E6) and early 7 (E7) genes, position 215–514 and 605–805. The specimens exhibited the same proportions of type 16 sequences specific for the tested regions. 8.8% (9/102) of normal samples showed amplification for HPV type 16 E6 and E7 regions, while 48.3% (14/29) of CIN biopsies were positive for the same gene sequences.     

High-risk human papillomavirus DNA testing and high-grade cervical intraepithelial lesions

OBJECTIVE: To explore the role of high-risk human papillomavirus (HPV) DNA testing in the improvement of the recognition of cervical cancer and precancerous lesions in women with abnormal cervical cytology. METHODS: A total of 2152 women with abnormal cervical cytology were submitted to both HPV DNA testing and biopsy guided by colposcopy and the results were correlated. RESULTS: Positive rate of high-risk HPV DNA in groups of atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells, cannot exclude high-grade (ASC-H), low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions was 53.7, 53.2, 84.6 and 93.0%, respectively. In each group, the detection rate of grade 2,3 cervical intraepithelial neoplasia (CIN 2,3) or cervical cancer in patients with positive HPV DNA was significantly higher than that with negative HPV DNA (P<0.05). In ASC-US group, the negative predictive value of high-risk HPV DNA testing for detection of CIN 2,3 and cervical cancer was 99.8% and the sensitivity 98%. CONCLUSION: HPV DNA testing is a useful indicator in the management of patients with ASC-US and plays an important role in the evaluation of risk for CIN 2,3 and cervical cancer.     

Screening history preceding a diagnosis of cervical cancer in women age 65 and older

Objective

To characterize the antecedent screening of women 65 years of age and older diagnosed with cervical cancer.

Methods

Screening histories of women 65 years of age and older who were diagnosed with cervical cancer between 2003 and 2008 were examined utilizing the organization's databases and the regional Cancer Registry. Stopping screening was recommended at age 65 for members who had either 3 consecutive negative Paps or a single negative Pap plus HPV test (“cotest”).

Results

From 2003 through 2008 there were 56 Kaiser Permanente Northern California members 65 years of age and older diagnosed with cervical cancer. During the same time period there were 1,323,100 woman-years of membership in women age 65 and older. The risk of invasive cancer among women age 65 and older was 4.2/100,000/year in 2003-2008. 33 of 56 (59%) had one or more Pap smears prior to diagnosis. Of the 33, 14 women (25%) had 3 consecutive negative Pap smears prior to diagnosis. Three of 46,401 women with 1 or more negative cotests at age 65 and older were subsequently diagnosed with invasive cancer during 132,639 women-years of follow-up (2.3/100,000/year).

Conclusions

Most cervical cancers diagnosed at age 65 and older occur in women who have not met our criteria for stopping screening. A few cancers will continue to occur at age 65 and older despite multiple negative tests, as is true in other age groups. We currently have no evidence that these cancers would be prevented with continued screening at ages 65 and older.     

Clinical validation of high risk HPV DNA testing versus ThinPrep cytology for primary cervical cancer screening

Objective(s)To compare the validity of the high risk HPV DNA testing using the hybrid capture II technique (HC-II) to ThinPrep cytology for primary cervical cancer screening.DesignCross sectional pilot study.SettingDepartment of Obstetrics and Gynecology, Taiba Hospital, Sabah Al Salem, Kuwait.MethodsConsecutive 1923 cervical smear samples were taken for ThinPrep cytological screening and hr-HPV DNA testing using HC-II assay. Histological diagnoses were obtained from a total of 426 women who had positive results on screening and a group of women with negative screening and suspicious cervix underwent colposcopy and directed biopsies, and those with cervical precancerous lesions or cancer received appropriate treatment.Main outcome measuresSensitivity, specificity, positive predictive value and negative predictive value of screening methods.ResultsHPV was found positive in 15.5% of cases. 19/22 cases (86.4.1%) with a biopsy diagnosis of CIN2+ had a HC-II positive test. For CIN3, HC-II was positive in all cases (100%). Assuming a similar specificity level, the relative sensitivity of the HC-II test was higher when histologically confirmed high grade lesions (CIN2+ or CIN3+) were observed. HC-II test had the best sensitivity when defining cases as CIN2+ or CIN3+ (98.7% and 100%, respectively). When using the ASCUS+ cytological cutoff, the differences in CIN2+ and CIN3+ sensitivity between HC-II test and ThinPrep cytology were statistically not significant. Specificity of the ThinPrep cytology for any low and high grade histological lesions was clearly >95% when cytological diagnosis LSIL+ cutoff was used and nearly 100% when HSIL+ cutoff was used. All these specificity estimates were high compared with HC-II test. The specificity of the ThinPrep cytology decreased with about 10% when ASCUS+ was the cutoff. At cutoff ASCUS+, specificity of HC-II was comparable or only slightly lower than with ThinPrep ASCUS+ cytology with no statistically significant differences.ConclusionsThinPrep smears and hr-HPV DNA detection by HC-II performed very well with regard to identifying high grade lesions. HPV DNA testing is a promising new technology for cervical cancer prevention and can be used for primary screening in conjunction with cervical cytology for women aged 30 years and older.     

宫颈癌发病的年轻化趋势与人乳头状瘤病毒感染的关系

目的探讨人乳头状瘤病毒感染与宫颈鳞状细胞癌发病年龄的关系.方法分析1992年1月至1999年10月在我院住院治疗的75例宫颈鳞癌患者的发病年龄,并对其肿瘤组织进行了HPV16E7检测.结果1992年1月至1999年10月宫颈鳞状细胞癌患者平均发病年龄逐渐减小;HPV16的感染率由25.00%上升到48.71%.年轻宫颈鳞癌患者HPV16的感染率(85.71%)明显高于年龄较大者(28.00%)(P＜0.01).结论随着HPV16感染率的升高,官颈鳞癌患者年轻化趋势愈明显,HPV16感染与官颈鳞状细胞癌年轻化有关.因此,对HPV感染的高危人群应加强监测、随访,作到早诊断、早治疗.     

Health-related quality of life and perception of anxiety in women with abnormal cervical cytology referred for colposcopy: an observational study

Objective

To evaluate health-related quality of Life (HRQoL) in patients with abnormal cervical cytology referred for colposcopy.

Study design

An observational study with prospective and retrospective cohorts. In the prospective arm 240 women referred for colposcopy filled in the 15D HRQoL and the State Anxiety Inventory (STAI) questionnaires and were followed up for 12 months. In the retrospective arm 208 patients who had been treated for cervical dysplasia eight years earlier filled in the 15D HRQoL questionnaire. Results were compared with the age- and sex-standardized general population.

Results

In the prospective part of the study, the mean 15D score of the patients did not differ from that of the general population. On the dimensions of sleeping, distress and sexual activity, however, the patients scored lower than the general population (p < 0.001). Patients with higher levels of anxiety at baseline, according to the STAI questionnaire, had lower HRQoL during the whole 12-month observation period (p < 0.001). The overall HRQoL score of the patients treated for cervical dysplasia eight years earlier did not differ from that of the general population.

Conclusions

Abnormal cytology and referral for colposcopy were associated with anxiety and slightly impaired psychosocial components of HRQoL but did not reduce the overall HRQoL. High anxiety levels at baseline were associated with impaired HRQoL. Previous treatment for cervical dysplasia was not associated with impaired overall HRQoL.     

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.

Study on the prevalence of human papillomavirus in the anal canal of women with cervical intraepithelial neoplasia grade III

Objective

The objective was to evaluate the prevalence of human papillomavirus (HPV) in the anal canal of women with cervical intraepithelial neoplasia (CIN) grade III.

Study design

Two groups were compared. In group I (study group), 40 women who had undergone cervical biopsy with a histopathological result indicating CIN III were evaluated. Group II (control) consisted of 40 women with normal results from colposcopic examination and colpocytological tests. The women in group I who presented high-grade neoplasia in colpocytological tests underwent collection of material from the uterine cervix and anal canal for investigating HPV DNA using the Hybrid Capture II^® technique. Colposcopy and cervical biopsy were then performed. If CIN III was confirmed, HPV DNA was investigated in the material collected. In group II, colpocytological tests and colposcopy were performed and, if normal, the procedure was similar to that followed for group I, except that no biopsy was performed.

Results

In group I, 39 women (97.5%) were positive for HPV in the uterine cervix and 14 women (35%) in the anal canal. In group II, only four women (10%) had a positive HPV test, for both the uterine cervix and the anal canal.

Conclusions

The prevalence of HPV in the anal canal of the women with CIN III was greater than in the women without CIN III.     

绝经后妇女宫颈病变的特点及其早期诊断

目的　探讨绝经后妇女宫颈病变的特点、筛查的必要性及早期诊断。方法　对北京大学第三医院自2 0 0 1年 1月至 2 0 0 4年 1月因宫颈涂片异常或临床检查可疑宫颈病变者 934例进行总结分析。根据绝经与否分为未绝经组和绝经组 ,对患者行宫颈涂片、阴道镜下宫颈多点活检。结果　未绝经组及绝经组宫颈异常涂片的检出率分别为 6 8 2 6 % (40 0 / 5 86 )及 85 31% (2 73/ 32 0 ) ,二组比较差异有显著性意义 (P <0 0 5 )。阴道镜下宫颈活检组织病理学诊断宫颈上皮内瘤变 (cervicalintraepithelialneoplasia ,CIN)分别为 2 4 34% (138/ 5 6 7)及 15 0 6 %(5 0 / 332 ) ,二组比较差异有显著性意义 (P <0 0 5 ) ;其中CINⅢ的检出率分别为 8 99% (5 1/ 5 6 7)及 8 73%(2 9/ 332 )。未绝经组与绝经组涂片及组织病理学提示人乳头瘤病毒 (humanpapillomavirus ,HPV)感染共 138例 ,其中高危型HPV阳性率分别为 6 2 2 2 % (5 6 / 90 )和 4 3 75 % (2 1/ 4 8) ,二组比较差异有显著性意义 (P <0 0 5 )。结论　为早期发现宫颈病变 ,阻遏疾病进展为宫颈癌 ,在绝经后妇女进行宫颈细胞学筛查是必要的。     

高危型人乳头瘤病毒检测在宫颈癌筛查中的应用价值

目的探讨将HR-HPV检测作为宫颈癌筛查手段的意义和价值。方法2004-12-2005-04对301医院妇产科门诊就诊的1231例患者,进行HPVDNA的杂交捕获法二代(HPV-HCⅡ)和液基细胞学(Thinprepcytol-ogytest,TCT)的检测,作为宫颈癌及其癌前病变的初筛。131例因细胞学异常,或细胞学正常而HPV检测阳性,或细胞学正常HPV阴性、而临床高度怀疑病变的患者行阴道镜下多点活检,结合病理结果进行分析。结果(1)1231例样本中,经TCT检测正常者1077例(87·43%),ASCUS32例(2·60%),ASCUS-H34例(2·76),LSIL73例(5·93%),HSIL15例(1·22%)。131例阴道镜下多点组织活检,病理证实炎症68例(51·91%),CINⅠ20例(15·27%),CINⅡ18例(13·74%),CINⅢ16例(12·21%),浸润癌4例(4·35%),湿疣5例(3·82%)。(2)HPV总感染率34%,HPV阳性者418例,年龄平均(36·93±10·8)岁,HPV阴性者813例,年龄平均(39·68±11·8)岁,HPV阳性组的年龄明显小于HPV阴性组,P<0·01。各病理组HPV感染率分别为:炎症58·82%,CINⅠ80%,CINⅡ72·22%,CINⅢ100%,浸润癌100%,湿疣60%。(3)阴道镜下多点活检结果:TCT和HPV均(-)者,无高度病变的发生;TCT(-)和HPV( )者中,≥CINⅡ的检出率11·1%(1/9),TCT异常和HPV阳性同时存在的病例中,≥CINⅡ的检出率最高40·5%(32/79);仅TCT异常而HPV(-)者13·2%(5/38),且5例均为CINⅡ,无原位癌和浸润癌的发生。结论持续的HR-HPV感染与宫颈病变的演进有关;HR-HPV检测是有价值的辅助诊断技术,与细胞学联合检测,为最佳宫颈癌筛查方案。     

Type-specific human papillomavirus DNA testing with the genotyping array: a comparison of cervical and vaginal sampling

Objective

To compare the detection and typing of human papillomavirus (HPV) between vaginal and cervical specimens by using polymerase chain reaction (PCR)-based reverse-blot genotyping arrays.

Study design

Two hundred and fifty-two women were referred to colposcopy clinics because of suspicious or positive results in a community-based cervical cancer-screening program. Genital tract cells were sampled from the cervix and self-collected from the vagina and tested with the HPV Blot kit.

Results

The HPV Blot kit identified HPV infection in 24.7% of vaginal specimens and in 30.2% of cervical collections. Cervical sampling detected significantly more infections compared to vaginal sampling only for HPV type 52; cervical sampling also detected significantly more high-risk HPV infection overall. The sensitivities of detecting histology ≥cervical intraepithelial neoplasia (CIN) grade 3 using the HPV Blot in vaginal and cervical specimens were 75.0% (95% CI, 47.6-92.7%) and 87.5% (95% CI, 61.6-98.4%), respectively (P = 0.48). Both sampling methods were thus statistically effective at detecting high-grade lesions and cervical cancer (P < 0.0001).

Conclusions

The HPV Blot yielded similar results for both vaginal sampling and cervical sampling in the detection of CIN grade 3 or worse. These findings indicate that self-sampling for HPV testing is a viable cervical cancer screening option.     

The evaluation of human papillomavirus DNA testing in primary screening for cervical lesions in a large Japanese population

To examine the utility of human papillomavirus (HPV) DNA testing for the screening of cervical cancer and its precursors, a prospective cohort study was performed in which a total of 8156 women with a median age of 36 years were enrolled. Two smear samples scraped from the uterine cervix were served for Papanicolaou test and HPV DNA testing (Hybrid Capture-II system). HPV-positive samples were further examined for HPV subtype using a DNA microarray chip. Women with cytologic abnormality or those with high-risk HPV DNA were further examined by colposcopy to determine histologic diagnosis. High-risk HPV DNA was detected in 11% of the general population, with higher prevalence of specific types, including 52, 16, 58, 51, 56, and 18. As expected, younger women were likely to have increased frequency of HPV infection. Notably, HPV DNA testing detected all 45 cases of cervical intraepithelial neoplasia (CIN) 3, while cytologic findings were negative in 6 of these cases. It is of particular interest that CIN was commonly associated with multiple HPV types, while invasive cancers had a single type of HPV. In terms of both sensitivity and positive predictive value in detecting the CIN, HPV DNA testing is superior to cytology. However, most importantly, HPV DNA testing in combination with cytology significantly improved the efficacy to CIN screening.     

Prevalence of human papillomavirus infection and correlation with cervical lesions in Japanese women

PURPOSE: To investigate the prevalence of human papillomavirus (HPV) infection in patients attending a gynecologic outpatient department, and to correlate the infection status with the presence or absence of uterine cervical lesions and the grades assessed by cytological or histological examinations. METHODS: Five hundred and seventy-two subjects were studied. In all subjects, HPV detection by the hybrid capture method and a cervical cytological examination were performed RESULTS: The HPV-positive rate in subjects with normal cytology was 12.3%. The detection rate was high (21.7%) in subjects aged in the twenties and low in the forties, and HPV was not detected in subjects aged in the sixties and seventies. When HPV-positive rates were examined according to cytological or histological grades, the rates were higher in subjects with abnormal cytology (P < 0.01) or cervical intraepithelial neoplasia (CIN) or squamous cell carcinoma compared with those with normal cytology. CONCLUSION: Diagnosis of HPV infection is also important for the prediction of progression to CIN and cervical cancer.     

人乳头瘤状病毒感染型别及多重感染与宫颈癌发病风险的关系研究

目的分析研究人乳头瘤状病毒(HPV)感染型别与宫颈癌发病风险的关系。方法回顾性分析2015年1月—12月液基薄层细胞学检查(TCT)联合HPV DNA检查进行宫颈癌筛查后,再进行阴道镜下宫颈组织病理检查的患者临床资料。结合患者的人口学信息,分析比较单一HPV感染及多重HPV感染型别分别与宫颈癌发病风险,其中以阴道镜下宫颈组织病理检查结果为金标准。结果 2 195名患者的检查结果显示,年龄是宫颈癌发病风险之一,TCT检测结果为低度鳞状上皮内病变(LSIL)或高度鳞状上皮内病变(HSIL),易发高级别宫颈上皮内病变和浸润癌,单一感染与多重感染患者间宫颈癌发病风险没有统计学差异(P0.05),HPV16型的感染率较高,无论患者是否为单一与多重感染,HPV16型都为宫颈癌发病风险,其OR值为6.27。结论需要重视38岁以上妇女的宫颈癌筛查,随着宫颈病变级别增加,HPV单一感染率与多重感染率无统计学差异,且宫颈鳞癌HPV感染倾向于单一高危型HPV16型。     

Cervical intraepithelial neoplasia in non-16/18 high-risk human papilloma virus positive/cytology negative women: An alternative approach in poor resource areas

ObjectiveBecause the specific prevalence and carcinogenesis of non-16/18 high-risk (hr) Human Papillomavirus (HPV) is not fully understood, we designed a study with aim of evaluating the risk of high-grade cervical intraepithelial neoplasia (CIN) in non-16/18 hr-HPV positive/cytology negative cases and assessing the distribution of non-16/18 hr-HPV subtypes.Materials and methodsThis cross-sectional study was conducted on 138 non-16/18 hr-HPV positive/cytology negative women, who were referred to the gynecologic oncology clinic of Yas hospital, affiliated with Tehran University of Medical Sciences, January 2021 to 2022.ResultsAmong the detected types, HPV 31 was the most frequent type. 63 cases underwent biopsy as indicated based on colposcopic examination with acetic acid 3% application among which 34 had normal results. In the remaining 29 cases, 25 had insignificant findings. CIN2 was reported in 2 cases, one with HPV 31, 45, 58, and the other with HPV 58. CIN3 was also detected in 2 cases, one with HPV 31 and the other with HPV 35, 45.The overall incidence of high-grade CIN was 2.8%. A statistically significant (P-value = 0.046) difference was detected between patients with high-grade CIN compared with the others regarding the Hookah usage.ConclusionThe risk of CIN among non-16/18 hr-HPV positive/cytology negative cases is noticeably low. Based on ASCCP guidelines return testing at 1 year without immediate colposcopy seems sufficient; however, because of many reasons doing immediate colposcopy rather than 1-year follow-up may be a more accessible approach in resource poor, low-income countries such as ours.