Human papillomavirus (HPV) type distribution in cervical carcinoma, low-grade, and high-grade squamous intraepithelial lesions in Venezuelan women

Objective

Cervical cancer is an important cause of mortality among women in developing countries, especially in the Latin America and Caribbean (LAC) region. Infection with high-risk (HR) human papillomavirus (HPV) has been identified as the primary cause of cervical cancer. The aim of this study was to determine the frequency of HR-HPV genotypes in low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical carcinoma (CC) among Venezuelan women.

Materials and methods

Subjects with histopathological diagnosis of LSIL, HSIL, and CC (LSIL = 200; HSIL = 100; CC = 150) were enrolled in the study after obtaining informed consent. Biopsy samples of these subjects were analyzed to determine the lesion type. HPV detection and typing was done using polymerase chain reaction (PCR) and reverse hybridization. HPV type specific prevalence was determined in subjects with single and multiple infections.

Results

HPV DNA was detected in 68%, 95%, and 98.7% of LSIL, HSIL, and CC cases, respectively. HR-HPV and low-risk oncogenic HPV (LR-HPV) was observed in 66.9%/11.8% of LSIL cases, 87.3%/3.2% of HSIL cases, and 91.2%/0.7% of CC cases. HPV types -16/-18 (65%) were the most common high-risk HPV types observed, followed by types -52, -33, -45, and -31.

Conclusion

Cervical cancer burden in Venezuelan women is substantial. HPV types -16/-18 were the most common types prevalent among Venezuelan women followed by types -52, -33, -45, and − 31 (prevalence, ~ 90.1%). The results of this study provide baseline information on the HPV type distribution, which may facilitate the development of a cervical cancer prevention and control program in Venezuela.     

High-risk human papillomavirus,other than type 16/18, in predominantly older Taiwanese women with high-grade cervical preinvasive lesions

ObjectiveTo investigate the various genotypes of human papillomavirus (HPV) in Taiwanese women patients with abnormal cervical cytology and analyze the associations between HPV types, cervical preinvasive lesions, and the medical characteristics of these patients.Materials and MethodsWe performed HPV genotyping GeneChip procedures and colposcopies for 784 women with abnormal Papanicolaou smears. The characteristics of the patients and the status of the HPV infection were correlated.ResultsA total of 706 (90.1%) of the 784 women were positive for HPV infection, including 641 patients with high-risk HPV (HR-HPV). Among the patients with high-grade squamous intraepithelial lesions (HSILs), the average age of the 273 patients with other HR-HPV types (48.6 ± 13.8 years) was significantly older than the 222 patients infected with HPV 16/18 (39.8 ± 11.8 years) (p < 0.001). The proportion of patients with HSILs who were older than 40 years and infected with other HR-HPV types (76.6%) was also significantly higher than those with HPV 16/18 (20.3%) (p < 0.001).ConclusionWomen older than 40 years and having abnormal Pap smears and HR-HPV infections other than type 16/18 should be managed carefully because of the risk for HSILs.     

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.     

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。     

Risk factors for human papillomavirus persistence among women undergoing cold-knife conization for treatment of high-grade cervical intraepithelial neoplasia

Objective

To investigate the risk factors potentially associated with high-risk human papillomavirus (HPV) persistence in women undergoing cold-knife conization (CKC) for treatment of high-grade cervical intraepithelial neoplasia (CIN).

Methods

Medical records of women who underwent CKC for treatment of CIN 2/3 between 2007 and 2012 at a tertiary hospital in Ankara, Turkey, were retrospectively analyzed. Cases involving persistent HPV infection after 1 year of follow-up were identified. Using univariate and multivariate analyses, the impact of various factors such as patient age, menopausal status, parity, high-risk HPV type, excised cone dimensions (width, height, and depth), and surgical margin status on high-risk HPV persistence was assessed.

Results

A total of 292 women underwent CKC for treatment of CIN 2/3 within the study period. After women with a subsequent diagnosis of cervical cancer, subsequent total hysterectomy, and inadequate follow-up data were eliminated, 113 women were eligible for final analysis. High-risk HPV persistence was detected in 24 (21.2%) women, and multivariate analysis revealed that patient age and cone depth were significant independent predictors (P < 0.05).

Conclusion

High-risk HPV persistence may be encountered after CKC procedures. It is important to evaluate persistent HPV infections after treatment because affected women are at increased risk for disease persistence, recurrence, and progression.     

Treatment of high-grade squamous intraepithelial lesions in an area of Thailand with a high incidence of cervical cancer

Objective

To audit the treatment of high-grade squamous intraepithelial lesions (HSILs) at Chiang Mai University Hospital based on 12 standard requirements of the National Health Service Cervical Screening Programme.

Methods

Records were reviewed of all women with histologically proven HSIL undergoing treatment at Chiang Mai University Hospital between January 2005 and May 2009.

Results

Four of the standard requirements were not met: not all women underwent colposcopy before definitive treatment; the rate of specimen fragmentation was high; among women with ectocervical lesions, the rate of tissue removal to a depth of greater than 7 mm was low; and among women aged over 50 years with endocervical-margin involvement, the rate of repeat excision was low.

Conclusion

This audit highlights four treatment practices that do not meet standard requirements and require detailed exploration. The development of guidelines for the treatment of cervical precancerous lesions in Thailand is challenging and merits further attention.     

Three-step versus “see-and-treat” approach in women with high-grade squamous intraepithelial lesions in a low-resource country

Objective

To investigate the frequency of cervical intraepithelial neoplasia (CIN) 2 or greater in women with high-grade squamous intraepithelial lesion (HSIL), and to evaluate whether colposcopically-directed biopsy is a necessary procedure for managing HSIL in a low-resource country.

Methods

A retrospective review was undertaken of women with HSIL on a Pap smear.

Results

Of 348 women who had undergone colposcopically-directed biopsies and loop electrosurgical excisional procedure (LEEP), 321 (92.2%) had CIN 2 or greater. Of these, 279 were diagnosed with CIN 2 or greater on biopsy as were 264 on LEEP. The lesions in women who had CIN 2, satisfactory colposcopy, and more biopsies were more likely to be completely excised by biopsy. The mean length of time between the initial Pap smear and LEEP was significantly longer than between the initial Pap smear and biopsy.

Conclusion

Women with HSIL can be effectively managed using the see-and-treat approach in a low-resource country owing to the frequency of CIN 2 or greater.     

Recurrent high-grade cervical lesion after primary conization is associated with persistent human papillomavirus infection in Norway

Objective

This retrospective registry-based study aimed to assess the human papillomavirus (HPV)-type distribution in primary and recurrent high-grade cervical intraepithelial neoplasia (CIN2 +), and to discriminate pre-existing from newly-acquired infections.

Methods

Cervical specimens from 58 women (median age (Q1–Q3): 37.6 (31.7–44.9)) who underwent primary (1998–2003) and repeat conizations were confirmed as CIN2 + during expert pathology review. HPV testing was performed using PCR MP-TS123 Luminex for 16 HPV types. Molecular HPV16 E6 and HPV18 LCR DNA sequencing was performed on specimens with persistent HPV16/18.

Results

All 58 paired cones were HPV positive; 49 had CIN3 + in the primary cone. Forty-seven (95.9%) women with primary CIN3 + and recurrent CIN2 + had persistent high-risk (hr) HPV infection, of which 74.5% were HPV16/18. Two women had probable newly-acquired HPV16/52/56 and HPV39 infections. One woman with persistent HPV52 also had a probable new HPV16 E6 variant in the recurrent CIN2 +. Median time delay (Q1–Q3) between conizations was 2.0 years (1.1–4.0), being shorter for women older than 40 years: 2.6 years (1.1–3.7) than for women younger than 40 years: 6.0 years (2.0–8.7). Primary conization histology revealed CIN3, cervical adenocarcinoma in situ and microinvasive carcinomas in 43 (87.8%), 5 (10.2%) and 1 (2.0%) women, respectively. Primary HPV16- and HPV18-infected CIN3 + had a shorter delay between conizations: 1.8 years (1.2–4.4) and 2.2 years (0.4–NE), respectively, compared to HPV33-: 3.8 years (3.3–7.8) or other HPV type-infected: 8.2 years (6.0–NE) CIN3 +.

Conclusions

Routine post-conization hr-HPV DNA testing together with cervical cytology may provide a better prediction for potential recurrent disease. Further, primary prevention through adolescent vaccination may prevent CIN2 + and its recurrence.     

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 of human papillomavirus in cervical swabs in the Okinawa Islands,Japan

Although human papillomavirus (HPV) is the main risk factor for invasive cervical cancer, the mechanisms of developing carcinoma are not entirely understood. In particular, the biology and natural history of HPV infection are still unknown. Therefore, we have investigated the incidence of human papillomavirus infection by polymerase chain reaction (PCR) in cervical swabs obtained from women who had cervical cancer screening in three separate areas of the islands of Okinawa. The prevalence of HPV in women aged between 30 and 85 years in the three local areas, Yonashiro-town, Naha-city, and Hirara-city, was consistent (9 to 10%). HPV of various oncogenic types, including HPV16, 18, 31, 33, 35, 35, and 58, were identified in HPV-positive swabs and the prevalence of these types varied in the three areas. Received: 21 August 2001 / Accepted: 18 November 2001 Correspondence to T. Maehama     

宫颈高度鳞状上皮内病变治疗后高危型人乳头瘤病毒的消退规律

目的探讨宫颈高度鳞状上皮内病变治疗后高危型人乳头瘤病毒(HPV)的消退规律,了解术后高危型HPV持续感染与病变残留或复发之间的关系。方法对2003年1月至2007年12月在广东省人民医院因宫颈高度鳞状上皮内病变行宫颈电环切除术的502例妇女的随访资料进行回顾性分析。结果术前存在高危型HPV感染的宫颈高度鳞状上皮内病变进行宫颈电环切除术治疗后,术后6、12、18、24个月HPV清除率分别为83.63%、94.39%、97.31%、98.88%。术后高危型HPV持续感染人群病变残留或复发率达26.85%。结论宫颈电环切除术后6个月高危型HPV己大部分消退,术后2年基本完全消退。术后宫危型HPV持续感染是病变残留或复发的高危因素,术后HPV阳性妇女,宜严密随访。     

High-grade histologic lesions in women with low-grade squamous intraepithelial lesion cytology from a region of Thailand with a high incidence of cervical cancer

Objective

To evaluate the prevalence of and predictors for underlying significant lesions in women with low-grade squamous intraepithelial lesion (LSIL) smears.

Methods

Records were retrospectively reviewed for 208 women with LSIL who underwent colposcopy and histological evaluation from October 2004 through April 2009.

Results

Mean age of the patients was 38.5 years. Forty-four (21.2%) women were nulliparous; 20 (9.6%) women were postmenopausal; 29 (13.9%) women tested positive for HIV. Thirty-three (15.9%) women were current users of combined oral contraceptive pills. The pathological results of initial colposcopic evaluations were: 63 (30.3%) with cervical intraepithelial neoplasia (CIN) 2-3; 62 (29.8%) with CIN 1; 4 (1.9%) with cervical cancer; and 79 (38.0%) with no epithelial lesion. Current use of combined oral contraceptive pills, a positive HIV test, and multiparity were significant independent predictors for high-grade disease.

Conclusion

Approximately one-third of women with LSIL in our population have underlying significant lesions. Current use of combined oral contraceptive pills, a positive HIV test, and multiparity are significant predictors for high-grade lesions.     

Value of human papillomavirus testing after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesions

OBJECTIVE: The aim of the study was to evaluate human papillomavirus (HPV) testing during the follow-up of patients after conization by loop electrosurgical excision for high-grade squamous intraepithelial lesion. METHODS: A prospective study was conducted on 205 patients who underwent conization for high-grade squamous intraepithelial lesion (CIN 2 or 3). Loop electrosurgical excision procedure (LEEP) was used in all cases. High-risk HPV testing was realized by the Hybrid Capture II system before and 3 months after conization. RESULTS: Of the 205 patients, 193 (94.1%) were positive for the HPV test before conization. Seventy-one were HPV positive after conization (34.6%). The margins were positive in 36.1%. Residual disease was observed in 27 cases (13.2%). Four patients (2%) developed a recurrence after a mean follow-up of 18.1 months (+/-12). There was no correlation between pretreatment HPV testing and the residual disease or recurrence. Patients with positive margins were significantly more likely to have residual disease than those with negative margins (P < 0.0001). Residual disease was more likely to occur when the posttreatment HPV test was positive (P < 10(-7)). All recurrences were observed in patients with a positive posttreatment HPV test (P < 0.05). Residual disease and recurrence were correctly predicted with a sensitivity of 81 and 100%, respectively, and a negative predictive value of 96 and 100%. CONCLUSION: Posttreatment HPV testing could be useful in the follow-up of patients after conization. In case of negative posttreatment HPV testing, the frequency of follow-up could be reduced, particularly in those patients with free margins.     

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.     

Human papillomavirus genotype prevalence in cervical biopsies from women diagnosed with cervical intraepithelial neoplasia or cervical cancer in Melbourne, Australia

Multicenter international phase III clinical trials using multivalent human papillomavirus (HPV) vaccines for cervical cancer (CC) prevention are underway. As HPV immunity is type specific, defining HPV genotype prevalence in different regions to ascertain whether predominant types differ geographically is considerably important prior to vaccine implementation. This study aimed to define HPV genotypes present in CC and high-grade dysplasia among women in Melbourne, Australia. HPV genotype analysis of a cross section of women in Melbourne with cervical dysplasia/cancer was performed. A total of 493 cervical biopsies from patients being treated for moderate (n= 122) or severe (n= 180) cervical intraepithelial neoplasia (CIN II/III) or CC (n= 191) were tested for HPV genotypes using the PGMY09/11 primer system and line blot assay. HPV detection rates were 63.9%, 72.8%, and 86.9% in CIN II, CIN III, and CC biopsies, respectively. The most prevalent HPV genotypes among CC biopsies were HPV-16 (52.9%), HPV-18 (18.3%), HPV-45 (6.3%), HPV-39 (3.1%), and HPV-73 (2.6%). Multiple HPV infections, comprising two to five types, were identified in 14.4% of biopsies, being significantly fewer (5.2%) among CC biopsies (P < 0.0001). These results indicate that the two most prevalent CC-associated HPV genotypes in Australia parallel those described internationally, with type variations thereafter.     

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).     

2341例妊娠妇女宫颈筛查及产后随访

目的:分析孕期妇女宫颈细胞学检查、HPV检测、活检组织病理结果及产后自然转归状况。方法:选择2009年1月～2010年2月在北京大学人民医院接受孕期产检及分娩病例,孕前半年未行液基细胞学(TCT)检测,孕早期或中期均进行TCT检查,结果异常者部分行人乳头瘤病毒杂交捕获Ⅱ代(HPVHC-Ⅱ)法检测,阴道镜检查及病理学检查。结果:(1)2341例孕妇中宫颈细胞学意义不明的非典型鳞状上皮细胞(ASCUS)及以上患者60例(2.56%),其中高度鳞状上皮内病变(HSIL)8例(0.34%),低度鳞状上皮内病变(LSIL)4例(0.17%),ASCUS48例(2.05%);细胞学异常者中25例行HPV检测,阳性18例(72%);细胞学异常者28例接受阴道镜检查,病理活检者21例;病理学结果宫颈上皮内瘤变(CIN)共13例(0.56%):CINⅠ3例(0.13%);CINⅡ2例(0.085%),CINⅢ8例(0.34%);(2)产后随访了51例,细胞学正常/炎症41例(细胞学转阴率80.4%),ASCUS8例,LSIL1例,ASC-H1例。孕期HPV阳性者,13例产后复查,4例仍为阳性,孕期与产后比较有显著性差异(P=0.004)。孕期CIN11例中,产后仍为CIN6例(CINⅠ1例、CINⅡ1例、CINⅢ4例),无早期浸润癌发生。结论:(1)妊娠期宫颈细胞学异常在产后有较高的转阴率,同时妊娠期存在较高的HPV亚临床感染,产后转阴率高;(2)妊娠期CIN患者在密切随访下继续妊娠是安全的;(3)妊娠期CIN患者产后应密切随访,若产后仍为CIN应尽快治疗。