Human papillomavirus genotyping as a predictor of high-grade cervical dysplasia in women with mildly cytologic abnormalities: a two-year follow-up report

High-risk human papillomavirus (HR-HPV) DNA testing has emerged as another testing modality for women with mildly cytologic abnormalities. We conducted a two-year follow-up study of 108 women with mildly abnormal cervical cytology for detection of CIN 2/3. A cervical swab sample was obtained for HPV genotyping by a HPV blot and histologic follow-up results were correlated with HR-HPV types. Of the 108 cases, 93 (86.1%) were positive for HR-HPV DNA. HPV-16 was detected in 45.1% of patients. CIN grade 2 or 3 was confirmed in 25 (23.1%) of the 108 women during the two-year follow-up period. The two-year cumulative incidence rates of CIN 2/3 were 38.6% (17/44) among HPV-16- positive women, but only 5.6% among HR-HPV-positive women without HPV-16 or HPV-18. The sensitivity of a positive HPV-16 test for CIN 2/3 was 68.0%, the specificity was 67.5%. Our results demonstrated that the type-specific HPV-16 test increased sensitivity of detecting high-grade cervical dysplasia for women who have mildly cytologic abnormalities. The implication of the present findings is that HPV genotyping may identify women with the greatest risk of high-grade CIN.     

Detection of human papillomavirus (HPV) genotypes in cervico-vaginal scrapes of women with normal and abnormal cytology

Background   Certain types of human papillomavirus (HPV) are associated with cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma. The study addressed the expression and detection of HPV genotypes in cervical and vaginal specimens of women with normal and abnormal cytology by polymerase chain reaction (PCR), each woman serving as her own control.
Methods   Study participants (127) were subgrouped into CIN-positive and CIN-negative, based on cytology screening, and endocervical and vaginal scrapes were collected by a gynecologist and placed immediately in saline. HPV DNA was assessed by PCR, and HPV genotypes were determined by hybridization of PCR products with type-specific biotinylated probes.
Results   Of the 127 participants, 55 tested positive and 72 tested negative for HPV DNA. While there was no difference between the two groups with regards to age or to number of pregnancies, higher numbers of smokers and of women with multiple sexual partners and abnormal cytology were seen in the HPV-positive group ( P  < 0.001). HPV DNA was detected in the vaginal scrapes of all HPV-positive, but in none of the HPV-negative women (sensitivity and specificity = 1.0). Furthermore, the HPV genotype was the same in vaginal and endocervical specimens in all the HPV-positive women.
Conclusion   HPV detection by PCR, using endocervical or vaginal sampling, is a sensitive and highly specific test for the identification of HPV infection, in particular in women with cytomorphologically normal cervices.     

The prevalence of different HPV types in Turkish women with a normal Pap smear

The age-specific human papillomavirus (HPV) seroprevalence and HPV type distribution in women with normal cervical cytology were studied. Cervical smear samples obtained using liquid-based smears from 582 clinically healthy women aged between 15 and 68 years from five centers from four different regions of Turkey, were studied between February 2010 and January 2011. Overall, 530 of the women with normal cytology were included and the samples were analyzed for the presence of HPV by AmpliTaq. Positive samples were typed further for 37 different HPV genotypes by a line blot assay. HPV was positive in 17.9% of the women. HPV prevalence was highest in the age group of 25-29 years (31.8%), and decreased with increasing age. HPV 16 was the most common type (3.6%) followed by type 6 (2.6%) and type 45 (2.2%). Types 11 and 18 were rare (0.6% and 0.4%, respectively). Among the risk factors, number of sexual partners and parity were positively correlated with HPV positivity. In the present study, a large number of sex partners and high parity increased the risk for HPV infection. The age-specific distribution of HPV in women with normal Pap smears did not show a U-shaped curve in contrast to European countries and the USA.     

Prevalence and genotype distribution of human papillomavirus in women with cervical cancer or cervical intraepithelial neoplasia in Henan province,central China

To evaluate the prevalence of human papillomavirus (HPV) infection and its genotype among women with cervical lesions in Henan Province, central China. A total of 1317 cervical scrapes from patients with cervical intraepithelial neoplasia 1 (CIN1) (n = 91), CIN2/3 (n = 466), and cervical cancer (CC; n = 760) were collected from 2013 to 2018, and then tested for HPV genotypes using polymerase chain reaction followed by flow-through hybridization assay. The prevalence of HPV was 62.64% for patients with CIN1, 86.91% for patients with CIN2/3%, and 89.21% for patients with CC. In total, the HPV prevalence was 86.56%, and the most common HPV type was HPV16 (58.77%) followed by HPV58 (10.33%), 18 (7.67%), 52 (6.61%), and 33 (5.54%). In this study, the high-risk HPV cumulative attribution rate of nine-valent vaccine coverage was markedly higher than that of bivalent or quadrivalent vaccine coverage in each histopathological category or overall (P < .001). Single HPV infection was the main infection category in each histopathological diagnosis, and the total infection rate was 65.83% (867/1317; P < .001). The prevalence of HPV16 or single HPV infection increased with the severity of cervical lesions (P < .001). HPV16, 58, 18, 52, and 33 may be predominant high-risk factors for cervical lesions in Henan Province. The nine-valent prophylactic HPV vaccine is more effective than a bivalent or quadrivalent vaccine for protecting women from CC in the region.     

The antigen-presenting environment in normal and human papillomavirus (HPV)-related premalignant cervical epithelium

The activation of HPV-specific T cells within the cervical microenvironment is likely to play an important part in the natural history of cervical intraepithelial neoplasia (CIN). The extent and the type of T cell activation will depend critically on the expression of MHC, costimulatory cell surface molecules and cytokines by keratinocytes and Langerhans cells within the cervical lesion. Expression of MHC class II (HLA-A-DR and -DQ), costimulatory/adhesion molecules (CD11a/18, CD50, CD54, CD58 and CD86) and cytokines (tumour necrosis factor-alpha (TNF-alpha) and IL-10) was therefore investigated by immunohistochemistry in normal squamous epithelium (n = 12), low-grade (n = 23) and high-grade (n = 18) squamous intraepithelial lesions of the cervix. CIN progression was associated with de novo expression of HLA-DR and CD54, and increased expression of CD58 by keratinocytes. However, significantly, there was no expression of any adhesion/costimulation molecule by epithelial Langerhans cells in any cervical biopsy studied. Furthermore, TNF-alpha, a potent activator of Langerhans cells, was expressed constitutively by basal keratinocytes in normal cervix (12+/12). but expression of this cytokine was absent in a number of CIN samples (20+/23 for low-grade, 12+/18 for high-grade CIN). Conversely, the suppressive cytokine IL-10 was absent in normal epithelium (0+/12), but was up-regulated in a number of CIN lesions (12+/23 for low-grade; 8+/18 for high-grade CIN). The restricted expression of costimulation/adhesion molecules and the nature of the cytokine microenvironment within the epithelium may act to limit effective immune responses in some CIN lesions.     

The prevalence of VAIN,CIN, and related HPV genotypes in Japanese women with abnormal cytology

Vaginal intraepithelial neoplasia (VAIN) is often found by chance. We investigated the prevalence of VAIN and related human papillomavirus (HPV) types in comparison with cervical intraepithelial neoplasia (CIN). This study enrolled 648 women who were referred to the outpatient clinic of Kanazawa Medical University Hospital for abnormal cytology from January 2009 to January 2019. HPV genotypes were determined using Genosearch-31 + 4, which can detect 35 different HPV types. Colposcopy was performed at the first visit by an experienced gynecological oncologist. Among 611 subjects with squamous cell lesions, 107 (17.5%) VAIN cases were identified, and 67 (11.0%) women had both VAIN and CIN. Ultimately, 72 VAIN1, 15 VAIN2/3, 203 CIN1, 249 CIN2/3, 32 cervical squamous cell carcinomas (SCC), and one vaginal SCC (Vag-SCC) were identified. The prevalences of VAIN1, VAIN2/3, and Vag-SCC were 35.5%, 6.0%, and 3.1% of equivalent cervical lesions, respectively. The VAIN patients were older than the CIN patients (P = .002). About half of the VAIN cases were diagnosed during the follow-up. Multiple HPV infections were found in 42.9% of the VAIN and CIN patients. HPV52, 16, 51, 53, and 56 were the most common types in VAIN, whereas HPV16, 52, 58, 51, and 31 predominated in CIN. HPV18 was rare in VAIN, HPV58 was more common in CIN than in VAIN, and HPV53 and HPV73 were more common in VAIN. In conclusion, VAIN1 was identified more frequently than we expected. Various HPV types were identified in the vagina, which is likely a reservoir for HPV.     

Genotyping of human papillomavirus in cervical intraepithelial neoplasia in a high-risk population

Infection with the human papillomavirus (HPV) is responsible for 99.7% of cervical cancers, the second most prevalent neoplasia in women worldwide and the fifth leading cause of death by cancer in this population. In Chile, the incidence rate is 14.4 cases per 100,000 women per year and it is considered a significant public health problem. The natural history of cervical cancer begins gradually from low-grade and high-grade squamous intraepithelial lesions to an invasive disease. In this study the frequency of HPV types was determined by HPV genotyping with reverse line blot hybridization in 200 cytobrushes of women with preneoplastic lesions in a high-risk population. HPV DNA was found in 89% of the lesions (83.3% of low-grade squamous intraepithelial lesions and 93.6% of high-grade squamous intraepithelial lesions). Multiple HPV infections were found in 14.4% and 15.5% of low- and high-grade lesions, respectively. HPV 16 was the most frequent genotype in single infections, followed by HPV 18. These results show that most of the preneoplastic lesions of the cervix (60%) were associated with HPV 16 and/or HPV 18, supporting the implementation of an HPV vaccination program in this high-risk population.     

Type‐specific human papillomavirus prevalence in cervical intraepithelial neoplasia and cancer in Iran

In Iran, human papillomavirus (HPV) vaccination is not currently included in the national vaccination program and there are no comprehensive approaches to cervical screening program. Regional data on distribution of HPV types in women is important to predict the impact of current HPV vaccines. Although several studies on distribution of HPV types in cervical precancer and cancer have been conducted in Iran, in most of them HPV positive samples were subjected to specific‐primer genotyping (mainly 16 and 18), and leaving the other HPV genotypes almost undetermined. Therefore, the present study aimed to investigate the distribution of HPV types in cervical neoplasia from West and Northwest of Iran. A total of 112 women with atypia, cervical intraepithelial neoplasia, and invasive cervical cancer were included. A PCR assay was performed in all samples to detect the presence of the HPV genome using the GP5+/6+ L1 consensus primer set. All HPV positive samples were subjected for sequencing. In overall, HPV prevalence was 20% in atypica, 44.5% in cervical intraepithelial neoplasia I, 92.3% in cervical intraepithelial neoplasia II‐III, and 98.2% in invasive cervical cancer. The most frequent HPV type was HPV 16 (79.2%), which was followed by HPV types 18, 6, and 33 at the frequencies of 6.5%, 5.1%, and 2.7%, respectively. The least HPV types were found to be 31, 45, 53, 58, and 66. In conclusion, this study shows that the current HPV vaccines could have great impact to reduce the burden of cervical cancer in Iran.     

Prevalence and genotype distribution of human papillomavirus in non-neoplastic cervical tissue lesion: cervical erosion

Human papillomavirus (HPV) infection is the commonest sexually transmitted infection, which is associated with various clinical conditions, ranging from asymptomatic infection to malignant disease of the cervix. The aim of this study was to evaluate the prevalence and genotypic distribution of HPV in women with cervical erosion and to compare the results with those in women with a clinically normal cervix. A further aim was to establish the association between HPV infection and cervical cytology results in women with and without cervical erosion. Cervical samples were collected by liquid-based method and consecutively evaluated for the presence of HPV DNA and for cervical cytology. HPV DNA was tested by a nested polymerase chain reaction (PCR) and typed by reverse dot blot genotyping. Cytological classification was made according to Bethesda 2001 criteria. The overall HPV prevalence was 16.9%; HPV DNA was positive in 20.2% of women with cervical erosion and 12.8% in women with normal cervix (P < 0.05). Multiple infections were found in 34.1% of the HPV-positive women. Commonest types were HPV 18 (32.9%), HPV 16 (29.5%), HPV 54 (20.5%), and HPV 6 (17%). Cervical cytology results were abnormal for 5.2% of women with cervical erosion and for 1.3% with clinically normal cervix (P < 0.05). This study detected a high prevalence of HPV infection in women with cervical erosion compared to women with a normal cervix. This data may contribute to the HPV epidemiology in the southeastern Turkey. It is recommended that women with cervical erosion should be given priority in HPV screening programs.     

Epidemiologic risk profile of infection with different groups of human papillomaviruses

This study identified the age‐specific prevalence and epidemiologic risk profile for infection with different groups and species of human papillomaviruses (HPV). Structured interview and HPV testing were conducted for 2,604 Chinese women self‐referred for cervical screening. Independent risk factors for infection were identified by multiple logistic regressions. Overall, a major peak of HPV infection was observed at women aged 26–30 years, and a minor peak at 46–55 years. This pattern was observed for high‐risk, low‐risk, and alpha‐5/7/9 HPVs; but alpha‐3/6 HPVs showed peaks of similar magnitudes in young and older women. Independent risk factors for HPV infection (all types combined) included younger age (OR [95% CI] for >55 vs. ≤30 years = 0.22 [0.09–0.55]; 31‐45 vs. ≤ 30 years = 0.57 [0.33–0.99]), having ≥4 lifetime sexual partners (2.28 [1.06–4.88]), and smoking (2.24 [1.22–4.10]). Young age and smoking were the most consistent independent risk factors observed across different HPV groups. The risk profile for high‐risk HPV was similar to alpha‐5/7/9. Single‐type infection was associated with having more sexual partners, higher education level and oral contraception; whereas multiple‐type infection was associated with smoking. In conclusion, a U‐shaped age‐specific prevalence curve was observed for HPV infection overall, but with a different pattern for different HPV species. Different HPV groups showed variations in their risk profiles. These data are useful for formulating preventative strategy for HPV‐related diseases. Catch‐up vaccination program in Hong Kong should cover a wider age group as the first peak of infection occurred relatively late. J. Med. Virol. 81:1635–1644, 2009. © 2009 Wiley‐Liss, Inc.     

Detection of human papillomavirus in sanitary napkins: a new paradigm in cervical cancer screening

Human papillomavirus was successfully detected by polymerase chain reaction (PCR) in menstrual blood or vaginal discharge collected in sanitary napkins in 100% of 17 women having koilocytosis, cervical intraepithelial neoplasia, or squamous carcinoma. We advocate this form of cervical cancer screening because of its high sensitivity and acceptance by patients.     

Human papillomavirus infection and invasive cervical neoplasia: a study of prevalence and morphology

The prevalence of human papillomavirus (HPV) DNA sequences in 45 cervical cancer biopsies was examined with the hot-start polymerase chain reaction (PCR), employing HPV consensus primers from the L1 region. The cases comprised 38 squamous cell carcinomas, three adenosquamous carcinomas, and four adenocarcinomas. PCR products were typed with single-strand conformation polymorphism (SSCP) and the HPV types detected were correlated with tumour type. Forty-three biopsies were HPV-positive, HPV16 being the most prevalent type. HPV18/33/45/58 were also detected, but no low-risk or multiple types. Keratinizing squamous cell carcinoma was invariably associated with HPV16 and adenosquamous carcinoma and adenocarcinoma with HPVs 18/45. Non-keratinizing squamous cell carcinomas harboured all five detected types. Our data corroborate the view that malignant cervical tumours are almost invariably associated with high-risk HPV and that certain malignant cervical tumour phenotypes correlate with specific HPV types. © 1997 John Wiley & Sons, Ltd.