Prevalence and risk factors for human papillomavirus DNA in cervical cytology

Objectives

This study aimed to detect the presence and prevalence of HPV-DNA in the cervical swab samples obtained from patients with cervical cancer, premalignant cervical lesions and benign cervical smear results, and to identify the potential risk factors influencing this prevalence.

Study design

Smear preparations were examined and classified according to the Bethesda system. HPV-DNA detection and genotyping was carried out using polymerase chain reaction combined with reverse hybridization line-probe assays. Age, smoking habit, age at first sexual intercourse, number of sexual partners, number of term births, contraceptive method, progesterone therapy, history of sexually transmitted diseases, history or existence of warts, existence of cervical infection and the history of circumcision of male sexual partners were recorded.

Results

Six hundred and forty-two women (96 women with abnormal cervical cytology and 546 women with normal cytology) provided cervical samples. Multiplex PCR testing revealed that prevalence of HPV-DNA was 38.9% in our study population. HPV-DNA was detected in 78.3% of the women with cervical cancer and 76.9% of the women with HGSIL. Abnormal cervical cytology was observed in 30% of HPV-DNA positive cases and in 5.4% of HPV-DNA negative cases. Our findings also indicate that smoking habit, number of sexual partners, history of sexually transmitted diseases, and abnormal cervical cytology were associated with HPV infection. With respect to parity, there was a decreased risk of HPV infection with the increase in the number of births.

Conclusions

Estimates of the prevalence of HPV infection vary greatly around the world, so the factors that contribute to the rare occurrence of cervical cancer after HPV infection might also differ from country to country. Information gathered from this study could be used to prioritize limited screening and treatment services given to woman who have specific characteristics that may put them at an increased risk of HPV disease.     

Prevalence and genotype distribution of human papillomavirus in women with cervical cancer or high-grade precancerous lesions in Chengdu, western China

Objective

To study the prevalence and genotype distribution of human papillomavirus (HPV) among women with cervical cancer or high-grade squamous intraepithelial lesions (HSIL) in western China.

Methods

Cervical cast-off cells from 144 women with cervical cancer and 63 women with HSIL were tested for HPV genotypes using an oligonucleotide microarray.

Results

The overall HPV prevalence was 80.6% in cases of carcinoma and 61.9% in cases of HSIL. The most common genotypes were HPV-16 (carcinoma, 68.1%; HSIL, 34.9%) and HPV-58 (carcinoma, 8.3%; HSIL, 17.5%). Other high-risk types included HPV-18, -31, -33, -35, -45, and -52, with HPV-18 more common in adenocarcinomas than in squamous cell carcinomas (21.4% vs 3.1%; P < 0.02). The HPV prevalence was lower among patients older than 49 years (P < 0.02).

Conclusion

The prevalence of HPV-16 and HPV-58 was high. This finding may help to improve HPV vaccination and cervical cancer prevention programs in western China.     

Distribution of human papillomavirus genotypes in women with cervical cancer in Slovenia

Objective

The purpose of the present study was to establish the distribution of human papillomavirus (HPV) genotypes in a representative population of women with cervical cancer in Slovenia in order to contribute to the lacking data on HPV in cervical cancer and to assess the potential local benefit of future prophylactic HPV vaccination.

Study design

A total of 284 samples of cervical cancer were analyzed including archival samples, cervical scrapes and fresh tissue samples. Polymerase chain reaction with GP5+/GP6+ primers was performed in all samples for HPV deoxyribonucleic acid (DNA) detection. All GP5+/GP6+ negative samples were additionally tested using CPI/CPIIg primers and INNO-LiPA HPV genotyping assay.

Results

After exclusion of 6 samples with unsuccessful amplification of beta-globin gene, 262 of 278 cervical cancer samples (94.2%) were HPV DNA positive. HPV genotypes found in the decreasing order of frequency were: HPV 16 (64.9%), HPV 18 (12.2%), HPV 33 (4.7%), HPV 45 (4.1%), followed by HPV 31, 51, 58, 59, 35, 52, 73 and 82 (3.5–0.2%). HPV positive samples were more frequent among squamous cell carcinomas than among adenocarcinomas/adenosquamous carcinomas (95.8% versus 85.5%; P = 0.003). HPV 16 was more frequently found in squamous cell carcinomas than in adenocarcinomas/adenosquamous carcinomas (69.9% versus 37.5%; P < 0.001), while the opposite was true for HPV 18 (6% versus 41.7%; P < 0.001).

Conclusion

Prophylactic HPV vaccination with currently available vaccines could prevent up to 77.1% of cervical cancer in Slovenia, which is caused by HPV 16 or HPV 18.     

Prevalence of high risk human papillomavirus types 16/18 in cytologically abnormal cervical smears in Alexandria,Egypt. A cytological and molecular study

IntroductionIn Egypt, cervical cancer ranks as the second most frequent cancer after breast cancer, among women between 15 and 44 years of age. High-risk human papillomavirus (HPV) 16 and 18 detection holds the potential to be used as a tool to detect women, at risk for consequent development of cervical cancer because of their predominance and potentially greater oncogenic nature than other high risk HPV subtypes.ObjectiveTo determine the prevalence of high-risk HPV 16/18 DNA in women with abnormal cervical cytology.Subjects and methods45 cases were collected from Egyptian women seeking routine gynecologic care. Ten cytologically normal cervical smear cell samples were included in the study as a control to be tested for the presence of HPV 16/18 DNA and were collected from asymptomatic patients having cystorectocele or coming for loop insertion or removal. The 45 specimens were subjected to real-time polymerase chain reaction, using multiplex HPV 16 and 18 PCR kit.Results45 cervical smears were collected in the present study. Cytopathological examination revealed that 5 (11.1%) were ASCUS, 8 (17.8) were LSIL, 5 (11.1%) were HSIL, 1 (2.2%) was squamous cell carcinoma (SCC), 1 (2.2%) was adenocarcinoma and 25 (55.6%) were benign (inflammatory). 20 patients with abnormal cervical cytology and 10 controls were included in the present study. In patients with abnormal cervical cytology, 5 (25%) were ASCUS, 8 (40%) were LSIL, 5 (25%) were HSIL, and 1 (5%) was SCC and 1 (5%) was adenocarcinoma. Statistical analysis revealed a significant difference between patient and control groups as regards regularity of menstruation where irregular menstruation and higher prevalence of menopausal women, abnormal vaginal bleeding, menorrhagia, vaginal infection, and abnormal cervical appearance were encountered in patients. A statistically significant higher prevalence of married women was found in the control group. There was no significant difference in the distribution of patients and control as regards HPV 16 or HPV 18 in which 20% of patients were HPV 16 positive and 10% of patients were HPV 18 positive compared with none in the control group. 6 were positive either for HPV 16 or 18, while 39 were negative. The HPV 16/18 positive patients had significantly higher age and marital duration when compared with HPV 16/18 negative group. Significantly, most of the HPV 16/18 positive patients were menopause. A significantly higher prevalence of women with cervicitis, contraceptive users and married women was in the HPV 16/18 negative group.ConclusionThe study generates epidemiological data of prevalence of HPV 16/18 in cytologically abnormal cervical smears in women seeking routine gynecologic care at the outpatient clinics of the Obstetrics and Gynecology Department at El Shatby University. High-risk HPV DNA testing by PCR of cervical samples diagnosed according to the Bethesda 2001 guidelines may benefit the management of patients with abnormal cervical smears, especially among women aged 46 years and older, in menopausal women and in women complaining of PMB. Therefore, HPV DNA testing should be made use of as an adjunct to cervical smears.     

Prevalence and genotypes' distribution of human papillomavirus in invasive cervical cancer in Saudi Arabia

Objective

Data concerning HPV infection in cervical cancer are globally lacking in Saudi Arabia. Therefore, the aim of this study was to assess HPV prevalence and genotypes' distribution in invasive cervical cancer in our patients to provide baseline information for screening and prevention.

Methods

The study included 100 paraffin-embedded cervical tumors. HPV genotyping was performed using the Linear Array kit (Roche Diagnostic) that enables the concomitant detection of 37 mucosal HPVs including 13 most common high-risk viruses.

Results

Eighty-nine specimens were HPV-positive. Eleven different HPV genotypes were detected, 8 high risk (16, 18, 31, 39, 45, 51, 59, 73) and 3 low risk (6, 64, 70). Ten patients had double infections involving mainly HPV-16 and 18. The most common genotypes were 16 (65.2%), 31 (7.9%), 45 (6.7%), 18 (3.4%), and 73 (2.3%). However, by considering double infections, HPV-18 became the second most common genotype (10.1%). The patients' median age was significantly lower (P = 0.028) in HPV-16/18 infected group compared to other genotypes (44, range 32-76 vs. 49, range 38-67).

Conclusions

Eighty-nine percent of cervical cancers in Saudi Arabia were associated with HPV infection, and 78.7% (70/89) of HPV-positive tumors were infected with HPV-16/18, which caused the cancer to appear 5 years earlier than the combined HPV-negative and other HPV genotypes (P = 0.013).     

Distribution of human papillomavirus genotypes in archival cervical tissue from women with cervical cancer in urban Sri Lanka

Objective

To identify the contributions of various human papillomavirus (HPV) genotypes in tissue samples from women diagnosed with cervical cancer in Sri Lanka.

Methods

In a retrospective study, archival cervical tissues samples (n = 108) obtained from Sri Lankan women diagnosed with histologically proven invasive squamous cell carcinoma between 2006 and 2007 were tested for HPV. Genotyping of HPV DNA was performed using an INNO-LiPA assay.

Results

Overall, 93% of tumor samples tested positive for HPV DNA. HPV types 16 and 18 accounted collectively for 83.4% of the positive samples.

Conclusion

The findings suggest that the HPV genotypes responsible for causing cervical cancer in Sri Lanka are similar to those reported elsewhere worldwide. Consequently, women in Sri Lanka could benefit from currently available prophylactic HPV vaccines should they be implemented.     

Acceptability of self-collected human papillomavirus specimens in cervical cancer screening: A review

Cervical cancer morbidity and mortality is an important public health problem around the world. Some of the barriers to cervical cancer screening include the embarrassment, discomfort, lack of privacy and time and cost associated with clinician-collected, clinic-based screening with cytology or human papillomavirus tests. Self-collection of a human papillomavirus (HPV) test has been found to be generally more acceptable, less embarrassing, more comfortable, more private and easy to do and preferred to pelvic examination for cervical cytology by many women worldwide. The most commonly reported limitation to self-collection is a woman’s lack of confidence in her ability to perform it correctly. Self-collected human papillomavirus tests have been shown to be as or more sensitive than cytology or clinician-collected HPV tests. With confidence-building education about self-collection, it is likely a viable method to extend the reach of screening in high and low-resource areas around the world.     

Usefulness of human papillomavirus testing in the follow-up of patients with high-grade cervical intraepithelial neoplasia after conization

OBJECTIVE: We aimed to define the adjunctive role of human papillomavirus (HPV) DNA testing in the follow-up of high-grade cervical intraepithelial neoplasia (CIN) after conization. STUDY DESIGN: We analyzed a consecutive series of 2,154 patients who received conization. Patients who had cone diagnosis of cervical cancer or CIN 1, a hysterectomy within 12 weeks after conization, and no follow-up data were excluded. The remaining 765 patients (monitored by Pap smears, colposcopy with or without high-risk HPV DNA testing) were analyzed. RESULTS: Of the 765 patients, 279 had CIN at cone margin or endocervix (group A) while 486 were both margin- and endocervix-free (group B). The 3-year cumulative rate of residual/recurrent high-grade CIN was 10.3% (95% CI, 6.9-13.7). HPV follow-up status (P=.015), margin status (P=.001), and follow-up cervical cytology (P<.0001) were significant predictors for residual/recurrent high-grade CIN by multivariate analysis. Four high-grade CINs and 1 microinvasive carcinoma of group A were detected initially by HPV testing, while 48.3% (199/410) of those without recurrent/persistent high-grade CIN still had persistent HPV infection. CONCLUSION: HPV DNA testing is useful in the follow-up and understanding of the natural history after conization for high-grade CIN.     

高危型人乳头瘤病毒检测在宫颈癌筛查中的应用价值

目的探讨将HR-HPV检测作为宫颈癌筛查手段的意义和价值。方法2004-12-2005-04对301医院妇产科门诊就诊的1231例患者,进行HPVDNA的杂交捕获法二代(HPV-HCⅡ)和液基细胞学(Thinprepcytol-ogytest,TCT)的检测,作为宫颈癌及其癌前病变的初筛。131例因细胞学异常,或细胞学正常而HPV检测阳性,或细胞学正常HPV阴性、而临床高度怀疑病变的患者行阴道镜下多点活检,结合病理结果进行分析。结果(1)1231例样本中,经TCT检测正常者1077例(87·43%),ASCUS32例(2·60%),ASCUS-H34例(2·76),LSIL73例(5·93%),HSIL15例(1·22%)。131例阴道镜下多点组织活检,病理证实炎症68例(51·91%),CINⅠ20例(15·27%),CINⅡ18例(13·74%),CINⅢ16例(12·21%),浸润癌4例(4·35%),湿疣5例(3·82%)。(2)HPV总感染率34%,HPV阳性者418例,年龄平均(36·93±10·8)岁,HPV阴性者813例,年龄平均(39·68±11·8)岁,HPV阳性组的年龄明显小于HPV阴性组,P<0·01。各病理组HPV感染率分别为:炎症58·82%,CINⅠ80%,CINⅡ72·22%,CINⅢ100%,浸润癌100%,湿疣60%。(3)阴道镜下多点活检结果:TCT和HPV均(-)者,无高度病变的发生;TCT(-)和HPV( )者中,≥CINⅡ的检出率11·1%(1/9),TCT异常和HPV阳性同时存在的病例中,≥CINⅡ的检出率最高40·5%(32/79);仅TCT异常而HPV(-)者13·2%(5/38),且5例均为CINⅡ,无原位癌和浸润癌的发生。结论持续的HR-HPV感染与宫颈病变的演进有关;HR-HPV检测是有价值的辅助诊断技术,与细胞学联合检测,为最佳宫颈癌筛查方案。     

Identification of Chlamydia trachomatis DNA in human papillomavirus (HPV) positive women with normal and abnormal cytology

Insofar as infection with human papillomavirus (HPV) and Chlamydia trachomatis (CT) are associated with cervical intraepithelial neoplasia (CIN), the aim of this study was to assess the correlation of HPV and CT infection in patients with normal or abnormal cytology. Endocervical samples from patients (n=121; mean age 33.7+7.0) were assessed for HPV and CT DNA by PCR. While there was no statistically significant difference between HPV-positive (n=44) and HPV-negative (n=77) patients to age pregnancies, higher proportion of smokers, patients with multiple male sex partners, or with abnormal cytology was seen in HPV-positive vs. HPV-negative women, respectively. An infection rate of CT of 21/44 was seen in HPV-positive as compared to 11/77 in HPV-negative patients. Within HPV-positive patients, there was no significant difference between CT-positive and CT-negative patients with regards to the risk factors studied. Collectively, this suggests that a causal relationship between HPV and CT infection in the development of CIN disease. Received: 1 August 2001 / Accepted: 25 September 2001     

Human papillomavirus infection and cervical ectopy.

OBJECTIVES: To investigate the prevalence of human papillomavirus (HPV), and HPV type 16 (HPV16) infection in cervical ectopy, and the presence of anti-HPV16 secretory IgA (sIgA) antibodies. METHODS: DNA from patients with cervical ectopy (n=218), HPV-associated lesions (n=111), and controls without evidence of cervical ectopy or HPV infection (n=93) were analyzed by PCR for the presence of HPV and HPV16. The presence of mucosal sIgA antibodies against HPV16 capsid antigens (VLP) was assayed in cervical mucus by ELISA. RESULTS: Prevalence of HPV DNA was higher in cervical ectopy than in controls (P=0.04; OR=2.06; 95% CI 0.99-4.33). HPV16 was 6.3 times more prevalent in cervical ectopy than in controls. Anti-HPV16 sIgA were detected more frequently in cervical ectopy patients than in controls (P=0.0004). CONCLUSIONS: Cervical ectopy correlates with HPV infection. HPV16 is highly prevalent in cervical ectopy. sIgA antibodies against HPV16 capsids are generated in patients with cervical ectopy.     

宫颈上皮内瘤变与人类白细胞抗原及人乳头瘤病毒感染相关性的研究

目的:探讨宫颈上皮内瘤变(CIN)与人乳头瘤病毒(HPV)感染及人类白细胞抗原(HLA)的相关性。方法:选取宫颈活检组织病理学诊断为CINⅠ42例、CINⅡ40例、CINⅢ29例、宫颈湿疣40例、慢性宫颈炎90例,从液基薄片检测剩余的保存液中提取宫颈脱落细胞学的基因组DNA,采用PCR方法及HLA试剂盒进行HPV16/18及HLA分型检测。结果:HPV16/18检出率CINⅠ组为21.4%,CINⅡ组为47.5%,CINⅢ组为55.2%,湿疣组为32.5%,宫颈炎组为1.1%。HLA分型表明,DR15(2)、DQ6(1)、DQ4在CIN组中阳性率分别为37.0%、44.0%、12.0%,明显高于宫颈炎组的17.5%、18.8%、3.8%(P<0.05),并且DR4阳性率随着CIN级别增高而增高(CINⅠ5.6%,CINⅡ13.9%、CINⅢ28.6%)。结论:HPV16/18感染和HLA分型与CIN及其分级密切相关,提示HLA在宫颈癌的发生、发展中可能起一定的作用。     

Human papillomavirus infection in couples with female low-grade intraepithelial cervical lesion

Low-grade squamous intraepithelial lesions (LSIL) are frequently found during cervical cancer screening. Usually they are associated with a human papillomavirus (HPV) infection. Does the high-transmission rate of HPV infection to the male partner represent a clinical risk for him? Are preventive measures to be taken to prevent the occurrence of male diseases?More than 80% of all LSIL are associated with HPV infections. The prevalence of HPV infection in males can range up to 40%, with 60% of the male partners of LSIL female patients presenting with penile flat lesions. The spontaneous cure rate for male infections is very high (90% at 5 years) but negative consequences in females (cervical high-grade lesion and cervical cancer) are frequent. Their male counterparts are far rarer but in some patients can require deleterious treatment. Transmission prevention by the use of condoms and circumcision is discussed. The effectiveness of HPV vaccination in this situation has not been validated.     

Telomere length in leukocytes and cervical smears of women with high-risk human papillomavirus (HR HPV) infection

ObjectivePersistent high-risk HPV (HR HPV) infection leads to the development of squamous intraepithelial lesions, which in turn may progress to cervical cancer. Telomere elongation or shortening may indicate a carcinogenesis process. In the present study, we analyzed telomere length from blood and cervical smears of women without and with high-risk HPV infection.Materials and methodsTelomere length was quantified by real-time PCR in blood and cervical smears from 48 women with high-risk HPV infection and HGSIL or LGSIL, 29 women HR-HPV positive without SIL, and 11 HPV-negative women.ResultsNo correlation was found between age and telomere length in blood and cervical smears. Women with high-risk HPV infection had shorter telomeres in cervical smears, but not in blood compared to the control group.ConclusionThese findings suggest that telomere shortening occurs in cervical cells of women with HR HPV infection both with LGSIL and HGSIL and may indicate the onset of carcinogenesis. In turn, there is no correlation between leukocyte telomere length and cervical cancer risk in women with HR HPV infection.     

Type-specific human papillomavirus DNA testing with the genotyping array: a comparison of cervical and vaginal sampling

Objective

To compare the detection and typing of human papillomavirus (HPV) between vaginal and cervical specimens by using polymerase chain reaction (PCR)-based reverse-blot genotyping arrays.

Study design

Two hundred and fifty-two women were referred to colposcopy clinics because of suspicious or positive results in a community-based cervical cancer-screening program. Genital tract cells were sampled from the cervix and self-collected from the vagina and tested with the HPV Blot kit.

Results

The HPV Blot kit identified HPV infection in 24.7% of vaginal specimens and in 30.2% of cervical collections. Cervical sampling detected significantly more infections compared to vaginal sampling only for HPV type 52; cervical sampling also detected significantly more high-risk HPV infection overall. The sensitivities of detecting histology ≥cervical intraepithelial neoplasia (CIN) grade 3 using the HPV Blot in vaginal and cervical specimens were 75.0% (95% CI, 47.6-92.7%) and 87.5% (95% CI, 61.6-98.4%), respectively (P = 0.48). Both sampling methods were thus statistically effective at detecting high-grade lesions and cervical cancer (P < 0.0001).

Conclusions

The HPV Blot yielded similar results for both vaginal sampling and cervical sampling in the detection of CIN grade 3 or worse. These findings indicate that self-sampling for HPV testing is a viable cervical cancer screening option.     

Urine-based human papillomavirus DNA testing as a screening tool for cervical cancer in high-risk women

Objective

To test the hypothesis that self-collected urine could be used to detect high-risk human papillomavirus (HPV) DNA with sensitivity and specificity comparable to those of standard cervical testing.

Methods

Women attending a gynecology clinic for evaluation of abnormal cytology were recruited. Fifty-two participants (21–60 years of age) collected urine samples, and clinicians collected cervical brush samples. When appropriate, cervical biopsies were obtained during colposcopy. HPV detection and typing were performed on DNA extracts from each sample, using commercial reagents for L1 consensus polymerase chain reaction (PCR) and type-specific hybridization. HPV 16 viral load was determined by quantitative PCR in HPV 16-positive samples. A diagnostic test analysis was conducted for urine samples.

Results

Fifty paired samples were analyzed, with 76% agreement between samples. The 12 discrepant pairs were all urine negative/cervix positive. The most common HPV types detected were 16, 51, 53, and 62. The urine test correctly identified 100% of the uninfected and 65% of the infected patients.

Conclusion

The results indicate that HPV DNA detection using urine is less sensitive than cervical sampling in a population with abnormal cytology. Further exploration is warranted to determine clinical utility when other options are unavailable.