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      Defining the validity of classical and non-classical cellular changes indicative of low-grade squamous intraepithelial lesion encompassing human papillomavirus infection in relation to human papillomavirus deoxyribonucleic acid testing

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          Abstract

          Background:

          Human papillomavirus (HPV) infection as of now has been beyond doubt to be the causative agent for cervical carcinoma. Its morphological identification in Pap smear is important.

          Aim:

          To define the validity of classical and non-classical cellular changes indicative of low-grade squamous intraepithelial lesion (SIL) encompassing HPV infection in relation to positivity for ‘high risk’ HPV16 as well as for ‘low risk’ HPV6/11.

          Materials and Methods:

          A total of 3000 Papanicolaou smears were screened, of which 150 were reported as low grade-SIL encompassing HPV infection (LSIL-HPV). Subsequently cervical scrapes from these 150 subjects, along with equal number of normal women as controls, were collected and processed for HPV deoxy-ribonucleic acid testing by polymerase chain reaction (PCR).

          Results:

          On the basis of cytomorphological characteristics in Pap smears, HPV infection were categorized into the following two groups: Classical (koilocytic) changes (CC) encountered in 30 women and non-classical changes (NCC) encountered in 120 women. It was observed that 21 (70%) CC and 46 (38.3%) NCC of HPV infection were positive for HR-HPV16; however only 12 cases (10%) of NCC and two cases (6.6%) of CC were positive for LR-HPV 6/11. Majority (41.7%) of HPV positive cases were reported in the age group of 25 to 30 years and HPV positivity decreased with the increasing age.

          Conclusion:

          Classical cellular changes are not the only diagnostic features for HPV infection in Pap smear, non-classical diagnostic features also support the diagnosis of HPV infection and may be positive for HR-HPV16.

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          Most cited references17

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          Age-specific prevalence of infection with human papillomavirus in females: a global review.

          Global data on age-specific prevalence of human papillomavirus (HPV) infection overall, and for high-risk HPV types 16 and 18, are essential for the future implementation of HPV prophylactic vaccines for cervical cancer prevention. A systematic review of peer-reviewed publications was conducted to summarize worldwide data on genital HPV-DNA prevalence in women. Studies with clear descriptions of polymerase chain reaction or hybrid capture detection assays were included. A total of 346,160 women were included in 375 studies. Of 134 studies with age-stratified HPV prevalence data (116 low sexual risk populations, 18 high sexual risk populations), over 50% were from Europe and the Middle East (38%) and North America (19%), with smaller proportions from Asia and Australia (21%), Central and South America (11%), and Africa (10%). Across all geographical regions, data on HPV prevalence were generally limited to women over 18 years of age. Consistently across studies, HPV infection prevalence decreased with increasing age from a peak prevalence in younger women (< or =25 years of age). In middle-aged women (35-50 years), maximum HPV prevalence differed across geographical regions: Africa (approximately 20%), Asia/Australia (approximately 15%), Central and South America (approximately 20%), North America (approximately 20%), Southern Europe/Middle East (approximately 15%), and Northern Europe (approximately 15%). Inconsistent trends in HPV prevalence by age were noted in older women, with a decrease or plateau of HPV prevalence in older ages in most studies, whereas others showed an increase of HPV prevalence in older ages. Similar trends of HPV 16 and/or 18 prevalence by age were noted among 12 populations with available data. Genital HPV infection in women is predominantly acquired in adolescence, and peak prevalence in middle-aged women appears to differ across geographical regions. Worldwide variations in HPV prevalence across age appear to largely reflect differences in sexual behavior across geographical regions. Further studies of HPV prevalence in adolescents are needed for all geographic regions.
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            Analysis by polymerase chain reaction of the physical state of human papillomavirus type 16 DNA in cervical preneoplastic and neoplastic lesions.

            Integration of human papillomavirus (HPV) DNA into the host cell genome is believed to be essential for malignant progression. However unambiguous detection of the physical state of HPV is a difficult and time-consuming procedure. To resolve this issue a simple, rapid and highly sensitive technique of polymerase chain reaction (PCR) has been utilized for detecting the physical state of HPV-16 DNA. Investigations were carried out in 122 cervical specimens comprising the whole spectrum of cervical lesions starting from cervical dysplasia to invasive carcinoma including HPV-16-positive normal controls. A pair of oligonucleotide primers specific to the E2 open reading frame, which is often deleted or disrupted following HPV integration, was used for the study. Distinction between episomal and integrated forms of viral DNA was accomplished by detecting amplification of the E2-specific fragment (1139 bp) in the PCR product. The PCR results were compared with those obtained by the conventional methods of Southern blotting, two-dimensional gel electrophoresis and chromosomal in situ hybridization; a high degree of agreement was observed between the methods. The findings indicate that although integrated forms of HPV-16 DNA were detected in more than 70% of cervical cancer specimens, integration was less frequent (23%) in severe dysplasia and carcinoma in situ. Only 2.5% of cases showed both episomal and integrated forms of HPV-16 DNA. The difference between episomal and integrated forms was statistically significant (P less than 0.01). The absence of integration in about 30% of cancer cases suggests that integration of HPV may not be necessary for malignant progression and alternative mechanism(s) of malignant transformation may occur without HPV integration. The PCR test thus provides an effective complement to Southern blotting and two-dimensional gel electrophoresis for accurate detection of the integration of HPV DNA.
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              Prevalence and incidence of human papillomavirus infection in women in the USA: a systematic review.

              A systematic review of studies published in the last decade was conducted to summarize data on the epidemiology of human papillomavirus (HPV) in the USA. A structured protocol was used to screen studies for review. Studies had to meet the following criteria: (1) the study was conducted in the USA, (2) the study population was predominantly adolescent women, (3) the description of the study's methodological and statistical methods is provided, and (4) the prevalence and/or incidence of HPV were clearly stated. The prevalence of HPV reported in the assessed studies ranged from 14% to more than 90%. The highest prevalence of HPV was identified among women attending sexually transmitted diseases (STD) clinics and college students, identifying them as target populations for prevention interventions. Conversely, the lowest HPV prevalence was among women in the general population. The review also revealed that HPV prevalence in African Americans is understudied, and the results of a few studies in this area are inconclusive.
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                Author and article information

                Journal
                J Cytol
                JCytol
                Journal of Cytology / Indian Academy of Cytologists
                Medknow Publications Pvt Ltd (India )
                0970-9371
                0974-5165
                Oct-Dec 2011
                : 28
                : 4
                : 159-164
                Affiliations
                [1]Department of Cytology, Institute of Cytology and Preventive Oncology (DHR), Noida, UP, India
                [1 ]Department of Molecular Oncology, Institute of Cytology and Preventive Oncology (DHR), Noida, UP, India
                Author notes
                Address for correspondence: Dr. Veena Kashyap, Department of Cytology, Institute of Cytology and Preventive Oncology (DHR), Plot I-7, Sector-39, Noida, UP, India. E-mail: veenakash@ 123456gmail.com
                Article
                JCytol-28-159
                10.4103/0970-9371.86340
                3214459
                22090688
                b8fce4be-cee8-4322-8d73-88bbf5df687d
                Copyright: © Journal of Cytology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Original Article

                Pathology
                koilocytes,pcr,lsil-hpv,hpv deoxyribonucleic acid,pap smear
                Pathology
                koilocytes, pcr, lsil-hpv, hpv deoxyribonucleic acid, pap smear

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