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Background and Objectives: Guidelines for the histopathologic diagnosis of human papillomavirus (HPV) infection have been drawn from changes seen in cervical specimens not necessarily applicable to penile epithelium.Goal: To evaluate histopathologic examination as a means of diagnosing HPV infection of the male genital tract.Study Design: Ninety-two consecutive male patients seen at the sexually transmitted diseases clinic. Twelve had condyloma acuminatum, and 80 had papular lesions, macular lesions, or both. Fifteen men without signs of HPV infection served as controls. Biopsy specimens were evaluated morphologically by light microscopy, and HPV DNA detection was performed by in situ hybridization and polymerase chain reaction.Results: All acuminate lesions were HPV DNA positive with in situ hybridization. Forty papular and/or macular lesions harbored HPV DNA, 28 (35%) of them positive with in situ hybridization and the other 12 (15%) positive with polymerase chain reaction. Morphologic signs attributed to HPV infection were found in HPV-positive and HPV-negative penile lesions, as well as in normal epithelium. In papular and macular lesions, the only criterion associated with HPV DNA positivity was neoplastic changes, which was present in 16 (40%) HPV DNA-positive specimens, compared to 4 (10%) HPV DNA-negative specimens (P < 0.01). Of the 16 lesions with neoplasia, 15 (94%) had detectable HPV DNA of a potentially oncogenic type.Conclusions: Histopathologic signs of HPV infection other than neoplasia seem to be of limited value. Detection of the infectious agent, in this case HPV, should be the gold standard for the diagnosis as it is for other infectious diseases. The strong association between neoplasia and potentially oncogenic HPV types makes this issue even more important. [ABSTRACT FROM AUTHOR]

High loads of human papillomavirus (HPV) 16 and HPV 18/45 increase the risk of developing invasive cervical carcinoma, revealing higher risk in percentiles of highest viral loads for HPV 16 (odds ratio (OR) 58.7, 95%confidence interval (CI) 21.9-151.4) compared to HPV 18/45 (OR 3.3, 95%CI 1.5-7.2). Thus, HPV load is a type-dependent risk marker for invasive carcinoma.British Journal of Cancer (2005) 92, 891-894. doi:10.1038/sj.bjc.6602436 www.bjcancer.com Published online 1 March 2005 [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine human papillomavirus (HPV) status and to investigate p16(INK4A) and Ki-67 expression and their correlation with clinical parameters and survival in women with primary carcinoma of the vagina (PCV).Methods: The presence of HPV DNA was evaluated by PCR. Genotyping was performed by Luminex in 68 short-term (2 years) and long-term (8 years) PCV survivors. p16(INK4A) and Ki-67 expression was evaluated by immunohistochemistry.Results: Human papillomavirus DNA was detected in 43% of patients, the majority (63%) of whom were HPV16 positive. High p16(INK4A) expression was significantly correlated with low histopathological grade (P=0.004), HPV positivity (P=0.032), and long-term survival (P=0.045). High Ki-67 expression was negatively correlated with histopathological grade (P<0.001) and tumour size (P=0.047). There was an association between HPV positivity and low histopathological grade, but not between HPV positivity and survival.Conclusion: High p16(INK4A) expression was associated with long-term survival, but the only independent predictors for survival were tumour size and histopathological grade. Our results indicate that p16(INK4A) and Ki-67 expression might be useful in tumour grading, and that it might be possible to use p16(INK4A) expression as a marker for HPV positivity, but this has to be further elucidated. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Lindell M, Sanner K, Wikström I, Wilander E. Self-sampling of vaginal fluid and high-risk human papillomavirus testing in women aged 50 years or older not attending Papanicolaou smear screening. BJOG 2012;119:245-248. Objectives To study the value of self-sampling of vaginal fluid at home in combination with high-risk human papillomavirus (HPV) testing in a cohort of older women not attending Papanicolaou (Pap) smear screening. Design Women ( n = 3618), aged 50-65 years, who had not attended screening for at least 6 years were offered self-sampling of vaginal fluid at home (study cohort). The collected material was analysed for the presence of high-risk HPV (using Hybrid capture 2; Hc2). Women with a positive HPV test were referred for colposcopy. These results were compared with the results of Pap smear screening in a corresponding age group of women (controls). The end point of the study was identification of a histological cervical intraepithelial neoplasia stage 2 (CIN2) and above (CIN2+). Results In all, 39.4% ( n = 1426) women participated and 4.6% ( n = 66) were high-risk HPV positive. Of the HPV-positive women 56 chose to attend a surgery (84.8%) after a mean time of 2.1 months and ten of these women (17.9%) showed CIN2+, corresponding to 0.70% of all participating women. In the controls, who participated in organised Pap smear screening, the prevalence of CIN2+ was 0.25% (15/6048). The odds ratio for identification of CIN2+ in women aged 50 years or older performing self-sampling and HPV test in comparison with Pap smear was: 2.84 (95% CI 1.14-6.77, P = 0.0174). In older women primary high-risk HPV testing (Hc2) and Pap smear screening showed equal specificity of around 96%. Conclusions Self -sampling of vaginal fluid in combination with high-risk HPV testing appears to be an attractive method to improve screening coverage and decrease the prevalence of cervical cancer in women aged 50 years or older. [ABSTRACT FROM AUTHOR]

Background: Testing for high-risk human papillomavirus (HPV) in primary screening for cervical cancer is considered more sensitive, but less specific, in comparison with Pap-smear cytology. Women with persistent HPV infections have a higher risk of developing cervical intraepithelial neoplasia 2+ (CIN2+) lesions. This study was performed to evaluate the gain in specificity for detection of histologically confirmed CIN2+ lesions achieved by short-time repeat testing for high-risk HPV in women aged 30-65 years, with the primary sample for HPV analysis taken by self-sampling.Methods: A total of 8000 women in Uppsala County, aged 30-65 years, who had not attended organised screening for 6 years or longer, were offered self-sampling of vaginal fluid at home and the samples sent for HPV typing. Of these, 8% (669) were not possible to contact or had performed hysterectomy. Women positive for high-risk HPV in the self-sampling test were invited for a follow-up HPV test and a cervical biopsy on average 3 months after the initial HPV test.Results: In all, 39% (2850/7331) of invited women chose to perform self-sampling of vaginal fluid at home. High-risk HPV infection was found in 6.6% (188) of the women. In all, 89% of the women testing HPV positive performed a follow-up examination, on average 2.7 months, after the first test and 59% of these women were HPV positive in the follow-up test. The prevalence of CIN2+ lesions in women with an initial HPV-positive test was 23% (95% CI 18-30%) and in women with two consecutive HPV-positive tests was 41% (95% CI 31-51%). In women with two positive HPV tests, the prevalence of CIN2+ lesions varied from 49% in women at age 30-39 years to 24% in women at age 50-65 years. Short-time repeat HPV testing increased the specificity for detection of CIN2+ lesions from about 94.2% to 97.8%. The most prevalent HPV types were HPV16 (32%), followed by HPV18/45 (19%) and HPV 33/52/58 (19%).Conclusion: The short-time persistence of high-risk HPV infection in this age group was about 60%. Repeat testing for high-risk HPV using self-sampling of vaginal fluid can be used to increase the specificity in the screening for cervical cancer in women aged 30-65 years. [ABSTRACT FROM AUTHOR]

Background: Around 65% of women with cervical carcinoma in Sweden have not attended an organised screening. We therefore investigated the value of using self-sampling at home in combination with a test for high-risk human papilloma virus (HPV) to increase participation.Methods: A total of 2829 women 30-58 years old, who had not attended the organised screening for > or = 6 years, were recruited. They were offered self-sampling at home (Qvintip) and recommended to send the collected vaginal fluid to a laboratory for analysis of the presence of high-risk HPV (Hybrid Capture 2 method).Results: A total of 39.1% of the women accepted home sampling. These women disclosed a relatively high prevalence of high-risk HPV, which decreased with age, from 11.1% in women 30-39 years old to 2.9% in women > or =50 years . Follow-up disclosed histological cervical intraepithelial neoplasm (CIN) 2-3 lesions in 43.2% of the women with a persistent HPV infection, corresponding to 2.0% of the total number of participating women. The sensitivity of a single smear to detect the histological CIN 2-3 lesions were only 52.6%, even if all abnormal smears (atypical squamous cells of unknown significance (ASCUS)-CIN 3)) were included.Conclusion: The use of self-sampling at home in combination with testing for high-risk HPV increases the participation rate of the organised screening and detects almost twice as many women with pre-malignant cell alterations (CIN 2-3) in comparison those with a single cytological smear. [ABSTRACT FROM AUTHOR]

Background: Most women with cervical cancer have not participated in Pap-smear screening. Self-sampling of vaginal fluid in combination with high-risk HPV testing may be a method to increase the attendance rate.Methods: A total of 4060 women, 39-60 years old, who had not attended the organised Pap-smear screening for 6 years or more were randomised into two equal groups. A study group was offered to self-sample vaginal fluid (Qvintip) at home and/or recommended to attend the Pap-smear screening. The collected fluid after self-sampling was examined for the presence of high-risk HPV (Hybrid Capture 2 method). Controls were only recommended to attend the Pap-smear screening. The end point was a histological identification of CIN2-3.Results: The participation rate was 39% (771 out of 2000) in the self-sampling group and 9% (188 out of 2060) in the conventional cytology (P<0.001). The number of histological CIN2-3 alterations detected was 0.4% (8 out of 2000) among women offered self-sampling of vaginal fluid and 0.07% (3 out of 4060) in women offered Pap-smears. The odds ratio (OR) for offering self-sampling and HPV testing instead of Pap-smear screening for detection of CIN2-3 was OR=5.42 (95% CI: 1.30-31.8).Conclusion: Offering self-sampling of vaginal fluid followed by a high-risk HPV test was considerably more effective for detection of histological CIN2-3 lesions in comparison with offering Pap-test in a midwife reception in women not regularly attending organised screening. [ABSTRACT FROM AUTHOR]

Background/aim: The main objective of microscopic examination of pleural effusions is to ascertain the presence of malignant cells. Effusions prepared routinely using May-Grünwald-Giemsa (MGG)- and Papanicolaou (PAP)-staining can, in a number of cases, provide inconclusive cytological results regarding malignancy., Patients and Methods: This report describes the refined diagnosis of such cases based on immunocytochemical analysis of pleural effusion cell blocks. Of the 340 pleural effusions obtained during 2019 at the Department of Clinical Cytology, Gävle Hospital, Sweden, 63 (18.5%) contained atypical cells of undetermined significance or potentially malignant cells., Results: This diagnosis could be refined using Epithelial Cell Adhesion Molecule/EPCAM (BEREP4) immunocytochemical analysis of effusion cell blocks, allowing previously inconclusive effusions to be classified as clearly benign 42/63 (66.7%) or malignant 21/63 (33.3%). Effusions initially diagnosed as clearly malignant (27/340; 7.9%) were all 27 (100%) BEREP4-immuno-stained. Most BEREP4-positive effusions (37/48; 77.1%) were also carcinoembryonic antigen (CEA) positive. The number of BEREP4-positive cells, however, tended to exceed that of CEA-positive cells. The BEREP4 positive effusions were further examined using different monoclonal antibodies, such as Thyroid transcription factor 1 (TTF-1) for primary pulmonary adenocarcinoma, to determine the original site of the primary tumour., Conclusion: Immunohistochemical staining of pleural effusion cell blocks significantly refines the diagnosis of serous pleural effusions, especially in cases where the preliminary diagnosis was atypical cells of undetermined significance or potentially malignant cells. Furthermore, in the cases of malignancy, the origin of the primary tumour could most often be determined., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: Accurate classification of lung carcinomas is crucial for selecting appropriate and adequate chemotherapy treatment. In this study, glandular (adenocarcinoma), and squamous cell differentiation were examined in non-small cell lung carcinoma (NSCLC) without obvious light-microscopic signs of squamous and glandular differentiation., Materials and Methods: All lung tumours diagnosed as NSCLC (n=61), without obvious squamous or glandular features, were obtained by bronchial biopsy or core biopsy supported by computed tomography. They were diagnosed during 1996-2009, at the Department of Pathology, Gävle Hospital, Sweden. The tumours were examined immunohistochemically with antibodies against CK5/6, p63 (squamous cell markers) and carcinoembryonic antigen (CEA) (adenocarcinoma cell marker). Double immunostaining (p63/CEA) was also performed on individual tumours., Results: The tumours originated from 36 males and 25 females, aged 54-83 years. Pure squamous cell differentiation (CK5/6 positive only) occurred in 34.4% (n=21) tumours and pure adenocarcinoma cell differentiation (CEA positive only) was present in 14.9% (n=9). Tumours with both squamous and adenocarcinoma features (CK5/6 and CEA positive) were most prevalent (47.5%, n=29). Two tumours (3.3%) were negative with both stains (and also synaptophysin negative). Double immunostaining (p63/CEA) revealed that squamous and adenocarcinoma markers were co-localised in cells in certain tumours., Conclusion: Co-localisation of squamous and adenocarcinoma markers in the same tumour cell suggests that additional analyses for novel biomarkers of specific lung cancer types may subsequently lead to a refined treatment choice for patients with the goal of improving clinical outcomes., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Self-sampling for HPV as part of primary screening is a well-tolerated method for women not attending organized Pap smear screening and could increase coverage of cervical cancer screening., Objective: To investigate if the prevalence of HR-HPV varies from day to day in infected women and if one single sample is reliable for detecting an ongoing infection., Study Design: This is a prospective cohort study on 12 premenopausal and 13 postmenopausal women performing daily self-sampling for HR-HPV testing. They were all HR-HPV-positive 1-3 months ago. Postmenopausal women were sampled for 28 days and premenopausal women sampled during bleeding-free days in one menstrual cycle. A possible difference in viral load between the estrogen-dominated proliferative phase and the progesterone-dominated secretory phase was analyzed., Results and Conclusions: Consistent results throughout the sampling period were observed for 19 women, with either a daily presence of HPV (14 women) or no HPV at all during the sampling period (5 women). Of 607 samples from 25 women, 596 were consistently positive or negative for HPV during the sampling period and 11 were inconsistent (2%). There was no difference in HPV copy number between the estrogen dominated proliferative or progesterone dominated secretory menstrual cycle phases. The major finding was a high degree of consistency concerning HR-HPV positivity and negativity of HR-HPV in vaginal fluid during a sustained period of daily self-sampling. It does not appear to matter whether the sample is collected in the proliferative or secretory phase., (Copyright © 2015 Elsevier B.V. All rights reserved.)