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Objective To examine the association between CD4 counts, HPV infection and the risk of cervical neoplasia among HIV-seropositive women. Methods A cross-sectional observational study was conducted among 1,010 HIV-seropositive women using cytology-based Pap smears. HPV DNA testing using Linear Array genotyping assay (Roche) was carried out in a subset of 191 patients. Multivariable-adjusted prevalence ratios (mPR) and 95% confidence intervals (CIs) were estimated with log-binomial regression. Results Among 1,010 HIV-seropositive women, the prevalence of AGC/ASCUS, LSIL and HSIL or greater was 8.3, 23.5 and 18.0%, respectively. The risk of cervical lesions was higher with CD4 500/mm3. HPV types 16 (41.7%) and HPV 56 (22.2%) were the most common types in HSIL cases. Women with CD4 levels

While two prophylactic HPV vaccines have been proven notably efficacious in clinical trials, the effectiveness of these vaccines at the population level remains to be evaluated. To lay the foundation for understanding the strengths and limitations of different endpoints for future effectiveness research, we present a comprehensive review of HPV-related clinical outcomes, including: (i) HPV type-specific positivity and persistence, (ii) Pap diagnoses (ASC-US, LSIL, and HSIL), (iii) histologic cervical cancer precursor lesions (i.e., CIN1, CIN2, and CIN3), (iv) invasive cervical cancer (ICC), (v) anogenital warts, (vi) recurrent respiratory papillomatosis (RRP), and (vii) other HPV-associated cancers (vulvar, vaginal, anal, penile, and oropharyngeal). While research on the vaccines' effects on these HPV clinical outcomes in the general population is presently limited, numerous large trials will soon be completed, making a priori discussion of these potential outcomes especially urgent. Furthermore, population level systems to track HPV-associated clinical outcomes may need to be developed for HPV vaccine effectiveness evaluation.

Objective To examine cells that were retained on sampling devices used to collect ThinPrep (Cytyc Corp., Boxborough, Massachusetts, U.S.A) Pap smears in order to evaluate both the number and significance of cells that are routinely discarded with these devices after liquid-based specimens are collected. Study design One hundred Pap smears from 100 women were prospectively procured after gynecologic Pap smears were collected for the ThinPrep Pap test. The sampling end of the collection devices was cut off and placed in a vial that contained SUREPATH preservative fluid (TriPath Imaging, Inc., Burlington, North Carolina, U.S.A). The residual cell samples were processed using the SurePath PREPSTAIN slide processor (TriPath). A single liquid-based slide was prepared from the sampling devices from each of the 100 specimens collected. The slides produced from the discarded devices were reviewed for the following: squamous cells, endocervical component, epithelial cell abnormalities and miscellaneous findings. The slides prepared from the "throw-away" (TA) material were subsequently compared with the primary ThinPrep Pap smear slide. Results Twenty-five percent of the TA samples had an equal or greater number of squamous cells per high-power microscopic field when compared to the primary ThinPrep slide, with 8% of the TA slides demonstrating greater overall cellularity. An endocervical component was present on 27 of 66 cervical samples (40.9%). Three of five cases (60%) interpreted as atypical squamous cells of undetermined significance had similar cells on the TA slides. Two cases of atypical glandular cells of undetermined significance had no abnormal cells on the TA slides. Twelve of 14 cases (85.71%) of low grade squamous intraepithelial lesion contained similar cells on the TA slides. Two of four cases (50%) of high grade squamous intraepithelial lesion also had similar abnormal cells on the TA slides. Miscellaneous findings included 1 case of benign endometrial cells and 4 Candida infections present on both preparations, along with 1 case of Trichomonas vaginalis organisms present on the ThinPrep slide only. In 1 specimen, several multinucleated histiocytic giant cells were present only on the TA slide. Conclusions Specimens prepared from TA collecting devices used for the ThinPrep Pap test are less sensitive than the primary specimen for the detection of cervical lesions. This is in contrast to split-sample studies involving ThinPrep and conventional smears. Our study documented the presence of normal and abnormal cells discarded from ThinPrep sampling devices in a high percentage of cases. Discarded abnormal cells on the TA slides were, however, few when compared to the primary specimen, with only 1 exception involving a high grade lesion.

Background Dedifferentiated chondrosarcoma is a rare, poorly understood and often fatal sarcoma that usually manifests as a high grade, non-cartilage-producing sarcoma juxtaposed against a low grade chondrosarcoma. A correct diagnosis requires recognition of both components. In the absence of complete resection, rendering a specific diagnosis on small biopsy specimens, such as fine needle aspiration biopsy (FNAB), may be extraordinarily difficult. Cases We retrospectively reviewed 4 cytology samples (3 primary, 1 metastatic) from 3 patients with dedifferentiated chondrosarcoma, initially analyzed by FNAB, emphasizing the potential for sampling error. Two women, aged 78 and 57 years, both of whom had prior histories of carcinoma, presented with lesions involving the right and left femur, respectively. One 27-year-old man with multiple osteochondromatosis developed a dedifferentiated chondrosarcoma of the left pelvis. Two primary cytologic specimens consisted of moderately cellular smears containing a spindled to polygonal, nonspecific, pleomorphic sarcoma unaccompanied by definite matrix material; 1 of these had a concomitant core needle biopsy (CNB), also demonstrating pleomorphic sarcoma. The third primary cytologic specimen revealed low grade chondrosarcoma, but a concomitant CNB showed only a high grade, non-matrix-producing sarcoma. The last patient developed a metastasis to the opposite femur; FNAB revealed a high grade spindle cell sarcoma. In none of the FNAB or CNB specimens were both low and high grade components of dedifferentiated chondrosarcoma recognized. However, the diagnosis was strongly suspected based on the clinical and radiographic findings. Conclusion Due to sampling error, the diagnosis of dedifferentiated chondrosarcoma may be difficult to establish by cytologic examination alone. Clinical and radiographic correlation is essential for an accurate diagnosis.

Background Cervical squamous intra-epithelial lesions (SIL) are more frequent in HIV-positive women overall. However the appropriate age at which to begin and end cervical cancer screening for early detection of lesions in HIV-positive women is not clear. We assessed the age-specific prevalence of any SIL and SIL requiring colposcopy in HIV-positive women in Cameroon. Methods We enrolled, interviewed and conducted conventional cervical cytology in 282 women, aged 19–68 years, initiating antiretroviral therapy in three clinics in Cameroon. In bivariable analyses, the crude relationship between age and the presence of lesions was assessed using locally weighted regression (LOWESS) methods. In multivariate analyses, generalized linear models with prevalence as the outcome, an identity link and a binomial distribution, were used to estimate prevalence differences. Bias analyses were conducted to assess the potential effect of inaccuracies in cytology. Results SIL were detected in 43.5% of the 276 women with satisfactory samples, 17.8% of whom had ASC-H/HSIL. On average, women aged 26 to 59 tended to have a slightly higher prevalence of any SIL than other women (Prevalence difference PD: 6.5%; 95%CI: -11.4, 24.4%). This PD was a function of CD4 count (heterogeneity test p-value =0.09): amongst patients with CD4 counts less than 200cells/uL, the prevalence was higher in patients aged 26–59, while there was essentially no difference amongst women with CD4 counts greater than 200 cells/uL. ASC-H/HSIL were present in women as young as 19 and as old as 62. Overall the prevalence of ASC-H/HSIL increased by 0.7% (95%CI: -3.8%, 5.1%) per decade increase in age. Conclusion Both severe and less severe lesions were prevalent at all ages suggesting little utility of age-targeted screening among HIV-positive women. Nevertheless, the long-term evolution of these lesions needs to be assessed in prospective studies.

Background HPV typing using formalin fixed paraffin embedded (FFPE) cervical tissue is used to evaluate HPV vaccine impact, but DNA yield and quality in FFPE specimens can negatively affect test results. This study aimed to evaluate 2 commercial assays for HPV detection and typing using FFPE cervical specimens. Methods Four large North Carolina pathology laboratories provided FFPE specimens from 299 women ages18 and older diagnosed with cervical disease from 2001 to 2006. For each woman, one diagnostic block was selected and unstained serial sections were prepared for DNA typing. Extracts from samples with residual lesion were used to detect and type HPV using parallel and serial testing algorithms with the Linear Array and LiPA HPV genotyping assays. Findings LA and LiPA concordance was 0.61 for detecting any high-risk (HR) and 0.20 for detecting any low-risk (LR) types, with significant differences in marginal proportions for HPV16, 51, 52, and any HR types. Discordant results were most often LiPA-positive, LA-negative. The parallel algorithm yielded the highest prevalence of any HPV type (95.7%). HR type prevalence was similar using parallel (93.1%) and serial (92.1%) approaches. HPV16, 33, and 52 prevalence was slightly lower using the serial algorithm, but the median number of HR types per woman (1) did not differ by algorithm. Using the serial algorithm, HPV DNA was detected in >85% of invasive and >95% of pre-invasive lesions. The most common type was HPV16, followed by 52, 18, 31, 33, and 35; HPV16/18 was detected in 56.5% of specimens. Multiple HPV types were more common in lower grade lesions. Conclusions We developed an efficient algorithm for testing and reporting results of two commercial assays for HPV detection and typing in FFPE specimens, and describe HPV type distribution in pre-invasive and invasive cervical lesions in a state-based sample prior to HPV vaccine introduction.

Background : Cervical cancer is the most common cancer in women in low-income countries. Although cervical cancer incidence and mortality is higher in HIV-positive women, resource limitations restrict the implementation of systematic screening programs in these women. We explored the potential for targeted screening by assessing the prevalence, severity and predictors of cervical squamous intra-epithelial lesions (SILs) in HIV-positive women in Cameroon. Methods and findings : We conducted a cross-sectional study of women on antiretroviral therapy in Cameroon. Socio-demographic, behavioral, and clinical information was obtained from eligible women. Cervical exfoliated cells were then collected, a conventional cytology performed and epithelial lesions classified according to the Bethesda 2001 system. A total of 282 women, aged 19–68 years, were enrolled in this study. The median CD4 count was 179 cells/microliter (interquartile range: 100–271). SILs were detected in 43.5% of the 276 women with satisfactory samples: including atypical squamous cells of unknown significance (ASCUS) 0.7%, low-grade SIL (LSIL) 25.0%, atypical squamous cells, cannot exclude high grade lesions (ASC-H) 14.5%, and high-grade SIL (HSIL) 3.3%. None of the demographic or clinical characteristics considered significantly predicted the presence of any SILs or the presence of severe lesions requiring colposcopy. Conclusion : The prevalence of SIL in women on antiretroviral therapy in Cameroon was high underscoring the need for screening and care in this population. In the absence of any accurate demographic or clinical predictor of SIL, targeted screening does not seem feasible. Alternative affordable screening options need to be explored.

Objectives Human papillomavirus self-tests that can be used at home and returned by mail may increase cervical cancer screening rates. Growing evidence suggests that self-test methods could increase screening for high-risk and hard-to-reach populations. The purpose of this study was to identify which self-test device women prefer and why. Methods Four focus groups were conducted with 30 high-risk women in two rural and two urban counties in North Carolina. Women evaluated three self-test devices: the Pantarhei screener (a lavage that releases liquid into the vagina and re-collects fluid), the Qiagen cervical brush (a brush that women insert into the vagina and is turned around to collect cells) and the Fournier cervical self-sampling device (a tampon-like plastic wand). Results The majority of women reported that they would use the brush (70%), followed by the wand (67%) and the lavage (43%). Women from urban areas appeared to prefer the brush, whereas women from rural areas endorsed the wand. Women reported liking the lavage because it seemed easy to use; they liked the wand because of its inviting colour (green), and liked the brush because of its small size and familiarity. Women reported disliking the lavage because the liquid seemed messy and unsanitary, disliked the wand due to the 15–20 recommended turns, and disliked the brush because it was short and the tip seemed abrasive. Conclusions No one device was perfect, although suggestions for an optimal self-test most resembled the brush. These findings can be used to develop an optimal self-test collector for women.

Objective To evaluate the epidemiology of the human papillomavirus (HPV) type and correlate it with the Papanicolaou smears in human immunodeficiency virus-seropositive women in Johannesburg, South Africa. Study Design In a cohort of 148 women, HPV DNA testing was performed with the Roche HPV genotyping test (Branchburg, New Jersey, U.S.A.). Papanicolaou smears were performed by standard cytology utilizing 2001 Bethesda reporting guidelines. Results The average age and CD4 count of the participants was 35 years and 255 cells per mm 3 , respectively. Fifty-four percent had abnormal Papanicolaou smears; 66% of the abnormal cytology was low grade changes, with 33 % assessed as having high grade changes. HPV DNA was found in 95% of the 148 subjects assessed, with 83% having 1 or more HPV oncogenic types. Common oncogenic types were 16, 35, 53 and 18. When HPV results were stratified by CD4, there was a significant risk of an oncogenic HPV type in women with CD4