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.     

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.     

Human papillomavirus testing as an optional screening tool in low-resource settings of Latin America: experience from the Latin American Screening study

Hybrid capture II (HC II) test for oncogenic human papillomaviruses (HPV) was carried out in a cohort of 4284 women at their first clinical visit. Overall prevalence of HPV was 17.1%, decreasing with age from 33.9% among women below 20 years to only 11.0% among those older than 41 years. HPV prevalence was significantly higher among current smokers (odds ratio [OR] = 1.31; 95% CI 1.1-1.6), in women with two or more lifetime sexual partners (OR = 1.9; 95% CI 1.6-2.4), and those women with two or more sexual partners during the past 12 months prior to examination (OR = 1.6; 95% CI 1.2-2.2). HPV detection increased in parallel with increasing cytologic abnormality, being highest in women with high-grade squamous intraepithelial lesion (P= 0.001). Specificity of the HPV test in detecting histologically confirmed cervical disease was 85% (95% CI 83.9-86.1). Sensitivity of the HPV test in detecting histologic abnormalities increased in parallel with disease severity, ranging from 51.5% for cervical intraepithelial neoplasia (CIN) 1 to 96.5% for CIN 3 and 100.0% for cancer, with respective decline of positive predictive value. These data suggest that HPV testing with HC II assay might be a viable screening tool among this population with relatively high prevalence of cervical disease.     

Cervical cancer screening practices of certified nurse-midwives in the United States

The purpose of this study was to determine how closely certified nurse-midwives in the United States follow contemporary cervical cancer screening guidelines. A survey was sent to 264 randomly selected certified nurse-midwives. Survey questions included demographics and clinical scenarios addressing initiation, frequency, and cessation of screening. Responses were received from 60% of the sampled certified nurse-midwives who had valid mailing addresses; 127 were eligible for the analytic sample. Many nurse-midwives initiate cervical cancer screening earlier than guidelines recommend; 72% would initiate screening in an 18-year-old within 1 month of coitarche, while 36% would begin screening virginal girls at age 18, and many continue cervical cancer screening after guidelines recommend cessation. More than 60% of the respondents would continue screening a woman who had undergone total hysterectomy for symptomatic fibroids who had no history of dysplasia, and half would continue to screen a 70-year-old woman with a 30-year history of previous normal Pap tests. In addition, despite guidelines which recommend less frequent screening, more than one-quarter (28%) would continue annual screening in a 35-year-old woman with three or more normal tests. Certified nurse-midwives are performing cervical cancer screening more frequently than current guidelines recommend. Comparisons to the practice of other providers are offered. Education to limit unnecessary testing is needed.     

Genital human papillomavirus screening by gene chip in Chinese women of Guangdong province

BACKGROUND: Human papillomavirus (HPV) infections are associated with cervical cancer. There were only a few reports and detailed data about epidemiological research of HPV infection in general population of China. AIMS: To determine the prevalence of genital HPV infection in Chinese women of Guangdong province. METHODS: A total of 1705 women were screened by gene chip. All HPV-positive women were further examined by ThinPrep liquid-based cytology test (TCT), and the cervical biopsies of those women with positive HPV-DNA and abnormal TCT were collected for pathological diagnosis. RESULTS: The overall HPV prevalence was 9.03% (154 of 1705), and 72.3% (126 of 154) of total positive samples were high-risk types, with higher prevalence of types 52, 58, 16, 18 and CP8304. For women aged 51 years or older, the overall high-risk HPV prevalence was 12.2% (24 of 179), which was obviously higher than those of other age groups (P < 0.05). CONCLUSIONS: Our results showed that the HPV prevalence in Guangdong is very similar to the world level. Unlike most previous studies, our findings suggest that HPV prevalence increased with age, and that the predominant genotypes in this area were HPV 52 and 58.     

Human papillomavirus

Human papillomaviruses are ancient small DNA viruses and represent the most common sexually transmitted infection in the world. In the majority, HPV infection is cleared by an incompletely understood immune response. HPV is a necessary but not sufficient cause of cervical cancer, and responsible for a proportion of other anogenital cancers including vulval, vaginal, anal and oropharyngeal. Oncogenesis is likely mediated through viral proteins which hijack host-cell machinery in epithelial keratinocytes and disrupt host tumour-suppressor proteins. Much work has been undertaken to further characterise the natural history of HPV infection and cervical disease. Such efforts have been translated to important public health interventions like the introduction of HPV tests in cervical screening. HPV vaccination programmes are expected to further reduce the incidence of high-risk HPV infections and resultantly HPV-related disease.     

Cervical screening strategies in resourced and resource-constrained countries

Screening for cervical cancer is well established in resourced countries, but in resource-constrained countries, it is almost non-existent at national level. In resourced countries, the Pap test forms the hallmark of screening, with the human papillomavirus DNA test a recent adjunct. In many resourced countries, however, screening for cervical cancer is still far from ideal. A coverage around 50% prevails in some countries, and few have reached the target of 80% or more. Furthermore, the human papillomavirus test and newly developed biomarkers may lead to the development of a 'super test', which could be applied less frequently compared with present-day cytological screening. In resource-constrained countries, the movement is towards a 'screen and treat' approach. The main screening methods under investigation are the visual inspection after diluted acetic acid application test and the human papillomavirus test. Cryotherapy and large loop excision of the transformation zone have been used most often as treatment methods. The ideal seems to be the human papillomavirus test with large loop excision of the transformation zone, provided a low-cost human papillomavirus test becomes available. Coverage is even a greater problem in resource-constrained countries, a problem in need of urgent attention. Resource-constrained countries, however, must curtail the high incidence of cervical cancer, which is often a lower priority than other pressing healthcare needs.     

Incorporating human papillomavirus testing into cytological screening in the era of prophylactic vaccines

Screening for, and treatment of, pre-cancerous cervical lesions has lead to dramatic reductions in cervical cancer in many countries. In all cases, cervical screening has been based on cytology, but that is beginning to change. Research studies, including randomised trials, clearly show that human papillomavirus (HPV) testing could be used to prevent a greater proportion of cervical cancer within a practical screening programme. Meanwhile, young adolescents are being vaccinated against HPV in developed countries, but cervical screening should continue for many years because it will take decades before most of those targeted by screening have been vaccinated. In the HPV vaccination era, the rate of cervical disease will decrease, and so will the positive predictive value of cytology. The screening characteristics of HPV testing make it the preferred choice for primary screening. However, questions regarding how to use HPV testing to screen vaccinated and unvaccinated women in the future remain unanswered.     

Human papillomavirus and cervical cancer from a prospective study in Khon Kaen, Northeast Thailand

The risk of developing carcinoma of the cervix in women infected with human papillomavirus (HPV) was estimated in a nested case-control analysis of 33 cancers (invasive and in situ) and 113 controls, matched by age and sex, from an ongoing cohort study of lifestyle and cancer in a rural population of Northeast Thailand. Oncogenic HPV types were present in 10.8% of control women and in 31/33 of the carcinoma cases, corresponding to an odds ratio of 130.6 (95% CI 11.7-1457.0). There was no significant difference in risk between prevalent cancer cases (diagnosed less than 3 months after HPV testing) and incident cases (diagnosed an average of 2.1 years later). HPV 16 and 18 were the most prevalent oncogenic HPV types present. The results confirm that some two of three of cervical cancer cases in this population of Northeast Thailand are caused by HPV 16 and 18.     

Human papillomavirus vaccination in the resourced and resource-constrained world

Human papillomavirus has been established as the causal agent for cervical cancer. The identification of a clear cause presents an unparalleled opportunity for cancer control. As such, the development of prophylactic human papillomavirus vaccines has been rightly hailed as one of the significant scientific triumphs of the past 20 years. This story of scientific triumph over disease, however, is not yet complete. The fruit of scientific labour must be delivered to the people in order to fulfil the underlying intent of the research (i.e. to prevent cancer and save lives). The success of a vaccination programme, however, does not depend on the biological efficacy of the vaccine alone. Various other local factors, such as poverty, gender inequality, cultural traditions, or religious beliefs, can significantly constrain the success of any vaccination programme. In this chapter, we provide an overview of how the human papillomavirus vaccine works and its global uptake, as well as, how variations in local contexts can affect the successful implementation of a vaccination programme. Other factors besides vaccine costs also need serious attention. With better understanding of such factors, policy makers and medical health professionals will be better equipped to make informed decisions to maximise the potential benefits of the human papillomavirus vaccines for the most number of people in individual countries.     

Human papillomavirus (including vaccination)

Human papillomavirus (HPV) is responsible for 99.7% of cervical cancer. Worldwide, cervical cancer causes more deaths than any other cancer, almost two per minute. 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; persisting infections can cause intra-epithelial neoplasia and invasive disease. Prophylactic HPV vaccines have been developed and prevent disease caused by the included HPV types. Current vaccines could prevent 70–75% cases of cervical cancer. The UK, in 2008 added HPV vaccination to the national immunization programme. 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 improving prophylactic vaccines to prevent more cases of cancer.     

Risk assessment and clinical impact of liquid-based cytology, oncogenic human papillomavirus (HPV) DNA and mRNA testing in primary cervical cancer screening (the FASE study)

Objective

New commercial HPV RNA assays require further validation studies in population-based cervical cancer screening settings.To assess the performance of (FDA-approved) APTIMA® HPV Assay (AHPV), Hybrid Capture 2 (HC2), in-house PCR genotyping, and ThinPrep LBC in population-based screening, stratified by three histological gold standards.

Study design

A multi-center trial in 5006 women undergoing routine screening in France was designed to compare the absolute and relative risks of diagnosing CIN3 + and CIN2 + lesions by different diagnostic tests.

Results

Reproducibility between the primary and second pathology reading was excellent for CIN3 + and CIN2 + endpoints (Cohen's kappa 0.948 and 0.854). Absolute risks (PPV) of different tests (AHPV, HC2, PCR genotyping, LBC) in diagnosing CIN2 + (15-20%) and CIN3 + (4-6%) were similar for the first, second, and consensus pathology readings. The relative risks of diagnosing these lesions by the four tests were also similar when the first, second or third pathology readings were employed. AHPV had the highest absolute risk of both histological endpoints, and detects 5% to 15% more CIN3 + and CIN2 + lesions, respectively, than LBC. Compared with HC2 assay, the relative risk of AHPV is 24% to 29% higher, with a significant difference in CIN2 + detection. With LBC as reference, AHPV had the best sensitivity/specificity balance measured by AUC (area under ROC curve) comparison test (significant for CIN2 +), and the colposcopy referral rate (9.2%) comparable to that of LBC (8.7%).

Conclusions

These data corroborate the suitability of AHPV for the primary cervical cancer screening.     

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.     

Human papillomavirus genotyping using HPV DNA chip analysis in Korean women

This study was designed to investigate the genotypes of human papillomavirus (HPV) in Korean women who had abnormal cervical cytology and to evaluate the clinical accuracy of HPV DNA chip analysis for the diagnosis of cervical neoplasia. Liquid-based cytology preparations, HPV DNA chip analysis, and cervical biopsy were performed in 2358 women. High-risk HPV was identified in 23.5% of 1650 histologically confirmed normal samples (including cervicitis and squamous metaplasia) and in 81.8% of 708 samples with cervical intraepithelial neoplasia (CIN) and carcinoma (P<0.01). The major prevalent high-risk HPV genotypes in 381 samples of CIN II/III were HPV-16, -58, -33, and -31, in order of prevalence rate (average overall, 78.0%), and HPV-16, -18, -58, and -33 (average overall, 81.2%) in 133 samples of squamous cell carcinoma (SCC). The infection rate of HPV-16 was significantly higher than that of other high-risk HPV genotypes in all normal, CIN, and SCC cases (P < 0.01) and increased with more advanced squamous cervical lesions (P<0.01). The detection accuracy of high-risk HPV using HPV DNA chip analysis for CIN II or worse was as follows: sensitivity 84% (81-87%), specificity 72% (70-74%), positive predictive value 47% (44-50%), and negative predictive value 94% (92-95%). These results suggest that HPV DNA chip analysis may be a reliable diagnostic tool for the detection of cervical neoplasia and that there are geographic differences in the distribution of high-risk HPV genotypes.