Mark Schiffman

..The stages of cervical carcinogenesis are better understood than for most other major cancers, providing a successful cancer etiology and prevention model...

..abstract:..

..Nevertheless, it is worth describing in broad terms for the readers of Cancer Cytopathology how successful, broad HPV vaccination of adolescent girls may affect cytology and HPV testing...

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..This article describes for open discussion an approach recently taken by a World Health Organization International Agency for Research on Cancer (IARC) Monographs Working Group to re-assess the carcinogenicity of different HPV types...

..Many additional analyses are underway...

..001). It appears that the natural history of HPV typically includes periods before and after cytologic abnormality, in which HPV DNA is the more sensitive indicator of infection...

..These results present several clear clues and research directions in our ongoing efforts to understand HPV carcinogenesis...

..If applied wisely, HPV-related technology can minimise the incidence of cervical cancer, and the morbidity and mortality it causes, even in low-resource settings...

..Larger viral genomic studies are warranted, especially to identify the genetic basis for HPV16's unique carcinogenicity...

..The minimal increases in sensitivity and in negative predictive value achieved by adding HPV types to DNA tests must be weighed against the projected burden to thousands of women falsely labeled as being at high risk of cervical cancer...

..The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment...

..The extent to which these observations can be translated into clinical practice must be rigorously examined in the context of the method of viral load measurement and the type-specific differences observed for incident >/=CIN2...

..In a large prospective cohort, we assessed the role of C trachomatis in cervical premalignancy and addressed confounding by HPV...

..The nonrandom distribution of multiple infections by case-control status and the apparent differential effect of viral load by genotype warrant caution when using HC 2 measurements to infer viral load associations with SIL and cancer...

..These findings suggest that the medical community should emphasize persistence of cervical HPV infection, not single-time detection of HPV, in management strategies and health messages...

..Investigations on the molecular distinctions along the disease continuum of cervical pathogenesis by HPV type are needed...

..These patterns need to be confirmed in other studies and populations. We suggest that these genetically distinct groups of HPV types may differ in tissue preferences, which may contribute to their differences in carcinogenic potential...

..Whereas our data support the diagnostic potential for p16INK4a, further prospective studies with detailed follow-up determining the prognostic capacity of this marker are needed...

..Our data support the need for a nonvisual diagnostic method to guide management and treatment of HPV-positive women...

..CONCLUSIONS: HPV screening that distinguishes HPV16 and HPV18 from other oncogenic HPV types may identify women at the greatest risk of > or = CIN3 and may permit less aggressive management of other women with oncogenic HPV infections...

..e., A3/A4/A15) may have a predilection for vaginal epithelium...

..We evaluated whether simultaneous screening with a Pap test and human papillomavirus (HPV) testing is useful for assessing the risk for cervical intraepithelial neoplasia (CIN) 3 or cervical cancer...

..Although genetic variation in TP53 might affect the natural history of HPV and cervical cancer, further work is needed to elucidate the possible mechanism...

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..Previous studies have failed to present data on or detect a broad spectrum of HPV genotypes and/or have not carefully sampled the vagina, instead relying on self-collection that is likely contaminated with cervical cells...

..These factors severely limit the clinical use of load measurements irrespective of HPV testing methodology...

..Lesion size seems to be an important determinant of colposcopy and biopsy performance. Genotyping for HPV16 in cervical cancer screening can improve risk stratification but may pose challenges to finding small lesions in colposcopy...

..Host genetic factors might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer, to persistent HPV infection, and hence to cervical precancer and cancer...

..We examined host genetic factors to identify those more common in individuals whose human papillomavirus (HPV) infections were most likely to persist and progress to cervical intraepithelial neoplasia grade 3 (CIN3) and cancer...

..The CIN3 is a substantially more reproducible diagnosis that can be validated more frequently with HPV tests and cytological interpretations than CIN2...

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..In some populations, HPV prevalence demonstrates a second peak in older women. Longitudinal data may help to explain this second peak...

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..We are now using these sharpened diagnostic categories to search for novel biomarkers predicting the risk of progression and invasion...

..The lack of evident severe abnormalities associated with HPV18 and related HPV types might have implications for screening for poorly detected glandular and alpha7-related lesions...

..Thus, persistence of HPV infection a median of six years after treatment was uncommon but, when present, posed a substantial risk of subsequent CIN2+. Serial follow-up data from other studies would further strengthen these conclusions...

..We developed a protocol to collect representative cervical specimens based on colposcopic evaluation from women treated with loop electrosurgical excision procedure (LEEP)...

..We were interested in comparing the performance of Linear Array (LA; Roche Molecular Systems) to Hybrid Capture 2 (hc2; Digene) for the detection of carcinogenic human papillomavirus (HPV) and cervical precancer...

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..Detailed descriptions of long-term persistence of human papillomavirus (HPV) in the absence of cervical precancer are lacking...

..However, these potential risk factors have not been adequately studied in prospective studies...

..We wanted to explore early HPV natural history and CIN 3 prospectively...

..However, the extent of methylation in other HPV types and its role in progression to cancer is poorly understood...

..Our findings support conducting comprehensive studies of viral load and cervical cancer precursors using quantitative LA genotyping data...

..Given the relationship between HLA-C and its receptors on natural killer (NK) cells, a role is proposed for NK function in human papillomavirus infection and cervical neoplasia...

..We investigated coinfection patterns for 25 human papillomavirus (HPV) types and assessed the risk conferred by multiple HPV types toward cervical disease...

..Here, we present the HPV genotypes found in first ∼500 cases of cervical intraepithelial neoplasia grade 3 (CIN3) or more severe disease (CIN3+) diagnosed at the study baseline...

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..The aim of this analysis was to assess the longitudinal relationship of abnormal cytology and HPV positivity in a 7-year prospective study of 2500 women in Guanacaste, Costa Rica...

..We evaluated determinants of seropositivity among 646 women infected with HPV-16 and/or HPV-18...

..Adding HPV testing to cytology is recommended for women ≥30 but long-term prospective studies of HPV testing are rare...

..The absolute risk of a subsequent abnormal Pap test for these women is uncertain. Therefore, the proper counseling and clinical management of these women is also uncertain...

..5% for WH) between the 2 groups of women. Although WH have a similar prevalence of carcinogenic HPV infection, compared with WNH without a cervix, they have minimal risk of HPV-induced cancer and are unlikely to benefit from HPV testing...

..Smoking cessation trials targeting this population might be warranted...

..Human papillomavirus (HPV) 16 and 18 infections cause most cases of anal cancer. We assessed efficacy of an AS04-adjuvanted HPV 16 and HPV 18 vaccine against anal infection with HPV 16, HPV 18, or both (HPV 16/18)...

..68 to 0.79). In conclusion, we suggest that HC3 (>/=0.6 RLU/PC) may be slightly more sensitive than and equally specific test as HC2 (>/=1.0 RLU/PC) for the detection of CIN3+ over the duration of typical screening intervals...

..Our novel approach to study multiple genotype infections in cervical disease with the use of unsupervised hierarchical clustering can address complex genotype distributions on a population level...

..We compared established risk factors among women with CIN2 and CIN3 to evaluate the heterogeneity of these factors in precancer and also assessed their role during cervical carcinogenesis...

..To improve our understanding of CIN3 natural history, we performed a detailed characterization of CIN3 heterogeneity in a large referral population in the US...

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..HC2 is likely more clinically specific, although possibly less sensitive, than either PCR test. Thus, use of HC2 on cervicovaginal specimens for screening could result in fewer referrals compared to LA and Amplicor...

..Both approaches are suitable for monitoring the impact of HPV16/18 vaccines in clinical trials...

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..Three-dose regimens for human papillomavirus (HPV) vaccines are expensive and difficult to complete, especially in settings where the need for cervical cancer prevention is greatest...

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..Infection with human papillomavirus (HPV) 16 or HPV18 elicits an antibody response, but whether the elicited antibodies protect women against subsequent infection by a homologous HPV type compared with seronegative women is unknown...

..Our data also suggest that studies reporting HPV DNA detection by PCR need to report the type of polymerase used, as well as other assay specifics, and underscore the need for worldwide standards of testing...

..73); among those with equivocal or abnormal cytologic findings, kappa values were 0.80 or more. These data show that HC2 is a reliable test for detecting clinically relevant oncogenic HPV DNA...

..3% (95% CI, 74.7-91.4%), respectively. We conclude that pooling specimens and testing by PCR may be useful for discriminating HPV DNA-positive from completely negative specimen sets in women who are likely to have been HPV DNA-negative.>..

..To analyze the effect of number of biopsies taken at enrollment with incident human papillomavirus (HPV) infections detected at the next 6-month visit...

..Our results indicate that an impairment in host immunologic responses is associated to persistent HPV infection. The fact that effects were evident for all studied stimuli is suggestive of a generalized effect...

..The impact of loop electrosurgical excision procedure (LEEP) treatment for cervical precancerous lesions on subsequent acquisition of new human papillomavirus (HPV) infections is not well described...

..Future analyses of cervical cytokine levels and HPV infection should control for the inherent variation of local cytokine levels due to hormonal influences, hemoglobin contamination, pH, and cervical secretion volume differences...

..Smaller amounts of material used in PCR could have limited its sensitivity, but our results demonstrate the importance of optimization and standardization of PCR-based assays for clinical applications...

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..Sexual behaviors have been linked to seropositivity for human papillomavirus (HPV) but not with the magnitude of the seroreactivity...

..001). These results indicate the underrepresentation of HPV18/45 in precancers, whereas HPV16-associated CIN3+ is diagnosed much earlier. Whether the underrepresentation of 18/45 may be due to occult pathology needs further investigation...

..The National Cancer Institute and National Library of Medicine are involved in a large effort to improve colposcopic assessment and, in preparation, are conducting methodologic research...

..In this article, we describe the perceived need for the resource and its components...

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..It is commonly believed that the sensitivity of Papanicolaou (Pap) tests decreases with a short interval between cytology samplings. To the authors' knowledge, there is only limited evidence to support this belief...

..There are few large case series describing the human papillomavirus (HPV) genotypes found in women diagnosed with rigorously reviewed cervical intraepithelial neoplasia grade 3 (CIN3), cervical precancer...

..These findings require confirmation...

..A competitive Luminex Immunoassay (cLIA) has been developed to measure neutralizing antibodies against human papillomavirus (HPV) types 6, 11, 16 and 18...

..68 and the linear-weighted kappa was 0.76. The results of this study indicate that HC 2 testing is reproducible even among cytologically normal women with low test values...

..We wanted to identify the most promising methylation marker candidates for cervical cancer early detection...

..In conclusion, hc2 cross-reacts with certain untargeted, noncarcinogenic HPV genotypes that are phylogenetically related to the targeted genotypes, but the degree of cross-reactivity may be less than previously reported...

..Infection with carcinogenic human papillomaviruses (HPVs) is necessary for cervical precancer and cancer, but the effects of type-specific HPV infection on cervical appearance are poorly understood...

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..Data from Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesion Triage Study were used to evaluate HPV persistence and reappearance after LEEP...

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..The Bethesda System (TBS) along with its companion atlas was updated in 2001 to improve standardization, clarity, and reproducibility of cervical cytology reporting...

..To estimate the agreement among multiple expert colposcopists evaluating high-resolution digitized cervigrams taken from patients with a variety of human papillomavirus (HPV) infection states and previous cervigram interpretations...

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