Colposcopy and cervical intraepithelial neoplasia

Cervical cancer is both preventable and curable. It has a long natural history with a prolonged pre-cancerous phase that is easily detectable and treatable. Exfoliative cytology has been the mainstay for screening of cervical intra-epithelial neoplasia (CIN). Assessment of women presenting with abnormal cervical cytology and the selection of those requiring treatment relied mainly on colposcopic impressions of the cervical transformation zone and the histological appraisal of directed punch biopsies. The need to maximise clinical resources, achieve quicker and more effective management of patients, limit postoperative complications and preserve reproductive function has led to the popularity of local excisional methods for cervical premalignancy. Although the cure rates for all local ablative and excisional methods are more than 90% after one treatment, the excisional methods provide a more reliable histopathological diagnosis and the patient can be treated at the initial visit. The recognition that persistent infection with oncogenic human papillomavirus (HPV) causes cervical cancer has led to the development of new HPV tests/biomarkers and prophylactic vaccines against HPV. The HPV DNA test that targets the viral DNA has been introduced as a test of cure after CIN treatment and as a triage tool in women presenting with borderline or low-grade findings at cytology. HPV DNA test will be introduced in primary screening in the future. The national HPV immunisation programme was initiated in the NHS in September 2008. The vaccines are safe, well tolerated and highly efficacious in HPV naive women.     

A study of women's knowledge regarding human papillomavirus infection, cervical cancer and human papillomavirus vaccines

AIMS: Human papillomavirus (HPV) infection is a common sexually transmitted viral infection and is associated with the development of cervical cancer. HPV vaccines are now undergoing phase 3 clinical trials in Australia. It is likely that an HPV vaccine will become licensed for use in the near future. METHODS: Ninety women aged 18-30 years from three different groups (those attending a dysplasia clinic, a local university health service and participants currently involved in a phase 3 HPV vaccine trial) completed a questionnaire assessing their knowledge base regarding HPV infection, cervical cancer, Pap tests and HPV vaccines. RESULTS: Respondents demonstrated good understanding of the Pap test and interpretation of an abnormal result. Most respondents (89%) had heard of HPV and attributed a number of different clinical symptoms to infection. For women who had not heard of an HPV vaccine, 79% of respondents stated that the most common resource they would use to obtain further information is their general practitioner. DISCUSSION: Many women do not understand the risk factors for HPV infection, the clinical problems it may cause and the potential long-term complications of infection. Few women have heard of a HPV vaccine, but most women surveyed would approach their general practitioner for more information if one became available. CONCLUSION: This study highlights the need for further education regarding HPV infection and the potential long-term complications such as cervical cancer. It also demonstrates that education of general practitioners regarding an HPV vaccine is essential, as this is the most likely resource women will use to obtain further information in the future.     

Molecular variants of human papillomavirus type 16 and risk for cervical neoplasia in South Africa

Non-European variants of human papillomavirus (HPV) type 16 are generally associated with a greater risk of cervical neoplasia than European prototype variants. We investigated whether this association would persist in a population in which non-European HPV 16 variants were more common. We sequenced HPV 16 isolates in cervical samples collected from 93 Black South African women enrolled in a cervical cancer screening study and examined associations between cervical neoplasia identified though colposcopy with cervical biopsy and the specific HPV 16 variant identified. The European prototype variant (EP) was the most commonly identified variant in this population (47% of all isolates), but African variants (Af-1 and Af-2) were also quite common (41% of all isolates). In contrast to previous studies, we found no evidence that non-European variants were associated with an increased risk of neoplasia. Rather, most of the HPV 16-associated cancers were found in association with EP (71% of 14 cases). In this setting where African HPV 16 variants were common, no increased risk for cervical neoplasia was found among women with these variants compared with other HPV 16 variants.     

Cervical cancer screening in low resource settings using visual inspection with acetic acid

Cervical cancer is one of the leading causes of death for middle-aged women in the developing world, yet it is almost completely preventable, if precancerous lesions are identified and treated in a timely manner. Cervical cancer screening based on cytologic examination is largely unavailable in developing countries or made available to a small, select group of women in private facilities, maternal child health sites, or family-planning clinics, missing the age groups at highest risk for precancerous lesions. Visual inspection with acetic acid (VIA) can be used to screen women. It can be done by nurses or midwives with appropriate training. Although still under investigation, research results show that VIA is simple, accurate, cost-effective, and acceptable to most women. This article reviews the natural history of cervical cancer and important aspects to consider related to cervical cancer screening in low resource settings. The VIA technique is described in detail.     

Prevention of cervical cancer

This article reviews the burden of cervical cancer in South Africa and shows that it remains the most common cancer among South African women, particularly women with least access to cervical cancer screening. It explains the rationale behind the South African cervical cancer screening policy, which is to offer all asymptomatic women three free cervical smears in a lifetime, beginning at age 30, 10 years apart. Further, it illustrates that cervical cancer screening offers unique opportunities for prevention at both the primary and secondary levels. The causal association of human papillomavirus infection of the cervix and the possibility for vaccination against the virus is discussed. The history of screening in South Africa and why it has failed to make a major impact to date on the morbidity and mortality of cervical cancer is also discussed. Finally, possible alternative approaches to cervical cytology for the prevention of cervical cancer are briefly reviewed.     

Cytology, liquid-based cytology and automation

Quality-assured, comprehensive, cytology-based population screening programmes have resulted in a substantial decline in the incidence of, and mortality from, cervical cancer. Cytology classification systems divide squamous cell abnormalities into low grade and high grade. Women with high-grade squamous abnormalities, cytology suggestive of glandular neoplasia, or invasive disease are referred immediately for investigation. Previously, the optimal management of women with low-grade cytology was uncertain. The introduction of liquid-based cytology has improved specimen adequacy and laboratory productivity, and also provided the platform for human papillomavirus testing for triage of low-grade abnormality, follow up after treatment and, ultimately, primary screening with triage to cytology, particularly in HPV-vaccinated populations. Liquid-based cytology is also ideal for automation-assisted reading of cervical cytology samples; however, recent studies have reported that automation-assisted reading is less sensitive than manual reading and does not reduce the risk of cervical cancer.     

河北丰宁地区妇女人乳头瘤病毒感染及疫苗认知状况调查

目的调查河北省丰宁满族自治县妇女人乳头瘤病毒（HPV）感染及对宫颈癌、HPV和HPV疫苗的认知情况,并探讨宣教对其认知度的影响。方法对河北丰宁地区717例18~45岁妇女进行HPV相关知识的问卷调查及宣教,对其中647例妇女留取宫颈脱落细胞进行高危型HPV DNA检测。结果高危型HPV总检出率为16.07%（104/647）;14.78%（106/717）的妇女曾听说过HPV,HPV知晓率与年龄、婚姻情况、户口类型及教育程度有关（P〈0.05）;84.38%（605/717）的妇女从未行宫颈癌筛查,在112例行宫颈癌筛查的妇女中,末次筛查为巴氏涂片、宫颈液基细胞学和HPV检测者分别为16.07%（18/112）、39.29%（44/112）和8.04%（9/112）;宣教后HPV知晓率显著提高（P〈0.05）;15.76%（113/717）的妇女既往听说过HPV疫苗,75.59%（542/717）的妇女倾向于接种医疗机构提供的疫苗,24.41%（175/717）的妇女倾向于接种政府或医药公司提供的疫苗。结论河北丰宁地区妇女HPV现患率较高,对HPV及宫颈癌的认知率偏低,宣教后人群认知程度显著提高,因此公众教育可以显著提高人群对HPV疫苗相关知识的认知水平。     

Impact of different educational interventions on psychosocial well-being of women with a positive high-risk human papillomavirus and normal cervical cytology: a randomised trial

Introduction: The aim of this study was to compare the effect of two educational interventions on the psychosocial well-being of Hong Kong Chinese women who have a positive high-risk human papillomavirus (HPV) test and normal cervical cytology.

Methods: Participants were randomised into either leaflet group, in which a written HPV factsheet was provided; or counselling group, in which a didactic HPV presentation in person in addition to the factsheet was provided. Women’s psychological conditions were assessed by self-administered questionnaires at pre, post (within one week) and 6?months after the educational interventions. Main outcome measures were psychosocial well-being (cervical cancer worry, anxiety and depression, screening-related anxieties, HPV-related shame) and knowledge of cervical screening and HPV.

Results: Data from 121 women (52 in leaflet group; 69 in counselling group) were analysed. There was no significant difference in the psychosocial well-being between the two groups at alltime points. Irrespective of the two educational interventions, cervical cancer worry and anxiety decreased over time. The counselling group had a significantly higher score in knowledge of cervical screening and HPV compared with leaflet group (mean score 4.65?±?0.19 versus 3.71?±?0.23, p?=?0.002) at post-educational intervention, but there was no significant difference (mean score 4.14?±?0.22 versus 3.58?±?0.24, p?=?0.084) at 6?months.

Discussion: Both educational interventions were comparable in relieving adverse HPV-related psychosocial effects. Combination of counselling and leaflet were more effective than leaflet only in improving women’s knowledge on cervical screening and HPV soon after educational interventions but the benefit was not apparent after 6?months.     

人乳头瘤病毒检测临床应用误区

高危型人乳头瘤病毒（HPV）的持续感染是宫颈癌和宫颈癌前病变发生的重要原因,HPV检测有效地提高了宫颈癌筛查的敏感度,是宫颈癌筛查的重要方法。但由于HPV检测方法众多,各种检测方法的设计、原理以及临床阳性阈值设定存在差异等因素,临床应用中容易存在误区。     

下生殖道感染与子宫颈细胞学异常的相关性研究

Objective?To study the association between abnormal cervical cytology and bacterial vaginosis (BV), vulvovaginal candidiasis(VVC), trichomonas vaginitis(TV), high-risk human papillomavirus(HR-HPV) infection in women attending cervical cancer screening. Methods?The study recruited 3 300 women aged 21 to 64 years of age who participated in cervical cancer screening. Demographic information was collected. Cervical exfoliated cell specimens were collected for liquid-based cytological diagnosis and HR-HPV detection. Reproductive tract secretions specimens were collected for molecular vaginitis diagnostics from women who were diagnosed with negative for intraepithelial lesion or malignancy(NILM) and all HR-HPV positive or ≥atypical squamous cells of undetermined significance(ASC-US). The Logistic multivariate model was used to analyze the risk factors of abnormal cervical cytology. Results?645 women were included in the study, including 408 NILM, 182 ASC-US, 23 low-grade squamous intraepithelial lesion (LSIL), and 32 high-grade squamous intraepithelial lesions (HSIL). The positive rate of HR-HPV (14.7%, 39.0%, 78.3% and 87.5%) increased with the severity of cytology (P<0.001). The prevalence of BV in different cytological diagnosis (34.1%, 49.5%, 60.9% and 43.8%) were significantly different (P<0.001), and the prevalence of BV in ASC-US were significantly higher than that in women with NILM (P<0.05). The prevalence of VVC in different cytological diagnosis (14.2%, 4.9%, 8.7% and 3.1%) was significantly different (P<0.01), and the ASC-US group was significantly lower than the NILM group (P<0.001). There was also a significant difference in the distribution of the prevalence of TV (2.5%, 9.3%, 4.3%, and 6.3%, P<0.01). The prevalence of TV in women with abnormal cytology was higher than that in women with normal cytology(P<0.05). The Logistic analysis showed that HR-HPV infection, BV, TV, VVC, lower level of education, and postmenopause were related to abnormal cervical cytology. Conclusion?HR-HPV infection is the determinant of abnormal cervical cytology. BV, TV, VVC, lower level of education, postmenopause, etc. may associate with abnormal cervical cytology.     

Prevalence of cervical cancer and feasibility of screening in rural China: a pilot study for the Shanxi Province Cervical Cancer Screening Study

Abstract. Belinson J, Qiao Y, Pretorius R, Zhang W, Keaton K, Elson P, Fischer C, Lorincz A, Zahniser D, Wilbur D, Pan Q, Li L, Biscotti C, Dawson A, Li A, Wu L, Ma CP, Yang XP. Prevalence of cervical cancer and feasibility of screening in rural China: a pilot study for the Shanxi Province Cervical Cancer Screening Study.
For cervical cancer screening to be feasible in developing countries, it must be accurate, inexpensive, and easy to administer. We conducted a pilot study in rural Shanxi Province, People's Republic of China, to determine disease prevalence and study feasibility in preparation for a large-scale comparative trial of 6 screening tests.
One-hundred and thirty-six nonpregnant women with no history of hysterectomy, pelvic radiation, or Papanicolaou tests were screened in a rural clinic. Ten percent of the women enrolled reported abnormal vaginal bleeding and 45% reported abnormal vaginal discharge. The tests were the Papanicolaou test (both conventional and ThinPrep), a self-administered swab test by Hybrid Capture II for high-risk human papillomavirus (HPV), a test for high-risk HPV from residual PreservCyt medium, fluorescence spectroscopy, and visual inspection of the cervix by a clinician. All women also underwent colposcopy and biopsies as the reference standard.
Biopsies showed 12 of 136 women had ≥ high-grade squamous intraepithelial lesions (HGSIL). Screening was completed in 5 half-day sessions, the procedures went smoothly, and local cooperation was enthusiastic.
Disease prevalence in Xiangyuan and Yangcheng Counties, Shanxi Province, can be estimated at 8.8% (95% CI, 4.5% to 15.0%). Screening 1000–2000 patients would be sufficient to detect a 10% difference in accuracy between diagnostic tests. The proposed large-scale trial is feasible.     

阴道上皮内瘤变28例临床分析

目的: 探讨阴道上皮内瘤变(VAIN)的临床特点、危险因素、诊治及预后。方法: 回顾性分析北京协和医院2005-2011年住院收治VAIN病例28例临床资料。其中VAINⅡ7例,VAINⅢ21例。结果: 患者年龄29～76岁(中位年龄48岁)。绝经21例(75%)。26例(93%)无临床症状。25例(89%)病变位于阴道顶端。27例进行超薄液基细胞学涂片(TCT)检查异常。23例人乳头瘤病毒(HPV)检测阳性。15例有子宫切除术史,其中因宫颈上皮内瘤变(CIN)和宫颈癌切除子宫10例。子宫切除术后至诊断VAIN时间：宫颈疾病平均3.1年,非宫颈疾病8.8年。不同级别VAIN在年龄、子宫切除原因、目前及既往合并宫颈疾病、TCT结果差异无统计学意义。28例全部进行手术治疗,3例术后复发。结论: HPV病毒感染、宫颈病变、宫颈病变或宫颈癌行子宫切除术史是VAIN的危险因素;细胞学-阴道镜-组织病理学适用于VAIN的诊断及随诊;宫颈病变切除子宫治疗后应密切随访,尤其是术后3年内应警惕VAIN。　　     

不同子宫颈癌筛查方案应用价值评价

目的评价不同方案进行宫颈癌筛查的临床应用价值。方法 2008年7月至2010年2月在中日友好医院妇科门诊同时采用宫颈液基细胞学检查（liquid-based cytologic test,LCT）和高危型人乳头瘤病毒（HR-HPV）筛查宫颈癌妇女1052例,对LCT提示≥ASC-US或HR-HPV阳性者或醋酸试验阳性者进行阴道镜下宫颈活组织检查,以病理结果为金标准评价LCT、HPV、LCT＋HPV平行试验、LCT-HPV系列试验、HPV-LCT系列试验5种方案筛查宫颈高度病变的价值。结果 LCT、HPV、LCT＋HPV平行试验、LCT-HPV系列试验与HPV-LCT系列试验筛查宫颈癌的敏感性分别为73.86%、93.18%、98.86%、90.34%和86.93%;特异性分别为90.87%、77.74%、71.57%、83.79%和86.76%;阳性预测值分别为61.90%、45.68%、41.13%、52.82%和56.88%;阴性预测值分别为94.54%、98.27%、99.68%、97.74%和97.06%;各筛查方案诊断价值相近,差异均无统计学意义（P〉0.05）;LCT-HPV系列试验的各项价值与LCT＋HPV平行试验相近,费用效益比更为理想。结论 LCT-HPV系列试验在获得良好筛查价值的同时显著降低了宫颈癌初筛的费用。     

Human papillomavirus update (including vaccination)

Human papillomavirus (HPV) is responsible for 99.7% of cervical cancer. Worldwide, cervical cancer causes more deaths than any other cancer, around one every two minutes. In the not so distant future cervical cancer may cause more deaths globally per year, (275,000 in 2008), than maternal deaths, (358,000 in 2008). Over 200 types of HPV have been identified. HPV is transmitted by skin-to-skin contact. Most HPV infections are cleared by the immune system; persistent infection may cause intraepithelial neoplasia and invasive disease.Prophylactic HPV vaccines prevent disease caused by the included HPV types and potentially prevent 70–75% cases of cervical cancer. The UK added HPV vaccination to the national immunization programme in 2008. The vaccines are safe and well tolerated. It is likely that the benefits will be seen over a 15–20 year period.Tests for HPV have been developed and are being evaluated as to their possible role in clinical practice.Research is ongoing regarding therapeutic HPV vaccination and second generation prophylactic vaccines to prevent more cases of cancer.     

Role of human papilloma virus testing in cervical cancer prevention

A clear causal relationship has been established between human papilloma virus (HPV) infection and the development of cervical cancer. Genital HPV infection is currently the most common sexually transmitted disease worldwide. The recent 2001 American Society for Colposcopy and Cervical Pathology Consensus Guidelines have included HPV testing for management of women with cervical cytological abnormalities. Clinicians now face the challenge of deciding when to use HPV testing in follow-up of abnormal Pap tests. This article includes updates on HPV, cervical cancer screening, and HPV testing technology. Recommendations for integration of HPV testing into clinical practice are provided.     

Colposcopy in special circumstances: Pregnancy, immunocompromise, including HIV and transplants, adolescence and menopause

The true value of colposcopy in pregnancy is under debate; the examination may be more difficult depending on the gestation at which a woman presents. Cervical intraepithelial neoplasia does not have an accelerated progression during pregnancy, and treatment is usually deferred until postpartum. The prevalence of cervical intraepithelial neoplasia is greater in women with immune compromise. Those with human immunodeficiency have a higher prevalence, more persistence and less regression of human papillomavirus-related infections. Cervical cancer remains an AIDS-defining illness. Women who have had renal transplants also have a higher risk of developing cervical intraepithelial neoplasia. By contrast, other chronic illnesses that require immunosuppressant therapy do not seem to show this added risk. In young women, human papillomavirus infection is common and cervical intraepithelial neoplasia is also evident, but regression of these lesions is frequent and so conservative review may be appropriate. At the menopause, colposcopy is often unsatisfactory. The use of human papillomavirus testing for triage of low-grade cytological abnormalities may benefit this age group.     

The use of human papillomavirus typing in detection of cervical neoplasia in Recife (Brazil)

Abstract. Lorenzato F, Ho L, Terry G, Singer A, Santos LC, de Lucena Batista R, Lubambo T. The use of human papillomavirus in detection of cervical neoplasia in Recife (Brazil).
High risk types of human papillomavirus (HR-HPV) play a major role in cervical cancer oncogenesis. This study aims to evaluate the efficacy of HPV detection and typing as a means of identifying cervical neoplasia in a high risk population. A management algorithm for implementation of HPV detection in clinical practice is also proposed. A nested case-control within a cohort study was undertaken in Recife (Brazil). All 479 participants had cervical scrapes collected for HPV detection followed by colposcopy. Samples were blindly analyzed by polymerase chain reaction (PCR) and typed by restriction fragment length polymorphism (RFLP).
HPV detection by PCR and typing with RFLP cost US$ 4.92 per woman screened in this study and is significantly better than cytology in identifying women at risk of developing cervical cancer ( P = 0.0001). Women who tested positive for HR-HPV had over 35-fold increased risk of having high grade squamous intraepithelial lesion (HSIL) or cervical cancer, although this does not necessarily translate into the same risk rate for women with latent HPV infection developing major cervical neoplasia. HPV typing offers 90% sensitivity and 85% specificity for cervical cancer detection. In combination with cytology it provides a negative predictive value of 99.4% and a sensitivity of over 96% for detection of HSIL and cervical cancer.
We conclude that HPV typing is an inexpensive and effective method for identification of cervical neoplasia and women at risk of developing it. It improves quality control for both false negative and false positive cytology results. Routine screening intervals could safely be increased to 3–5 years, decreasing anxiety and socio-economic inconveniences.     

老年女性子宫颈癌筛查及子宫颈病变的处理

老年女性仍有较高的罹患子宫颈癌的风险,受多种因素致其子宫颈癌筛查不足且缺乏专门针对老年女性的筛查及处理指南,现行的子宫颈癌筛查指南中对不能满足停筛条件的老年女性,由于存在患病的风险,应当继续进行筛查,已达成共识。目前,那些满足停筛条件的老年女性,65岁为其终止筛查年龄的建议受到了争议。对于老年女性的子宫颈癌筛查及子宫颈病变的处理应注意充分利用机会性筛查,且在进行阴道镜检查及活检时应充分考虑到老年女性的特殊性,对于老年性阴道炎明显患者可在检查前2周局部使用雌激素;不满意的阴道镜检查时应利用特殊的暴露及活检技巧等。文章通过复习文献并结合自身经验成文,以期对临床老年女性子宫颈癌的筛查和子宫颈病变的处理提供帮助。     

Human papillomavirus,cervical screening and ethical considerations

Human papillomavirus (HPV) is an extremely prevalent virus linked to multiple cancers, but most notably cervical cancer. The cervical screening programme in the UK has developed significantly since it was first introduced in 1964. This, together with the introduction of HPV vaccination, has made a huge difference to the early diagnosis and mortality for cervical cancer patients. Uptake of screening is paramount and this article addresses the barriers to this, and how these might be overcome. Other ethical issues around the topic of HPV, vaccination and screening include discrimination around sexual behaviour and orientation, education, vaccination availability and vertical transmission. This is an area of medicine that continues to develop and evolve as we understand more about HPV and how to tackle it.     

Cervical Cancer Screening and the Immunosuppressed Patient: the Issues in Screening High-Risk Populations

Purpose of Review

While evidence-based guidelines are available for cervical cancer screening in the general population, women at higher risk of persistent HPV infection and cervical cancer are excluded. There is limited evidence to guide screening practices for “high-risk” women, in particular, those who are immunosuppressed.

Recent Findings

Women with immunosuppression demonstrate an increased risk of cervical dysplasia and invasive cervical cancer (ICC) compared to the baseline population. Women with HIV were found to have increased rates of ICC and recurrent dysplasia, compounded by lower CD4 counts. Women with other forms of immune suppression demonstrated variable risk of dysplasia and cancer with the highest risk in transplant recipients and variable risk of dysplasia reported in autoimmune diseases. Data support updated screening guidelines for women with HIV: annual cytology for 3 years, and if screening is negative, increased screening intervals to every 3 years. However, women with HIV and other forms of immunosuppression have been reported to be less compliant with screening guidelines.

Summary

While there is high-quality data to support screening intervals for women with HIV, we were not able to identify data to guide modality and interval of screening in other types of immune compromise. Compliance with screening is lower both in women with HIV and other immune-mediated disease. Improving screening compliance in this high-risk population with a simplified screening strategy is likely the most important factor for reducing the risk of cervical cancer and further research is needed.