Study of the demographic criteria and management of adolescents referred with abnormal cervical smears.

This observational study was conducted on the adolescents referred to a colposcopy clinic in a UK general hospital over a period of 10 years (1996 - 2005). It included 155 newly referred adolescents (age < or = 20 years) with abnormal smear results. The aim of the study was to define the demographic risk factors associated with the development of abnormal cervical smears and identify the incidence of high-grade cervical lesions in this age group. All the risk factors associated with development of HPV infection were found among this group, particularly early age of sexual contact and number of sexual partners. A total of 52.9% of the cases had a smear showing moderate or severe dyskaryosis. The incidence increased to 66.7% among those who had their first sexual contact before the age of 16. Colposcopy and histology confirmed the presence of CIN II and CIN III in 40.6% of cases. The study showed that patients can develop high-grade cervical lesions in their early teens. Delaying the age of onset of cervical screening to 25, as it is currently recommended in UK, will delay the detection and treatment of these cases. A new approach is required to deal with this problem.     

Human papillomavirus in women. A three-year experience in a county hospital colposcopy clinic.

The human papillomavirus (HPV) has been associated with cervical dysplasia and carcinoma. This report summarizes the authors' experience with HPV-related problems over three years, 1987-89, while managing 1,644 women at a county hospital colposcopy clinic. Probes for HPV DNA were not used, and the diagnoses were made with cytologic and histologic criteria alone. The percentage of patients referred to the clinic with HPV found on routine Papanicolaou smears rose significantly, from 3 in 1987 to 18 in 1989. Fifteen percent of those referred because of HPV on a Papanicolaou smear were found to have cervical intraepithelial neoplasia (CIN) grade II or III after they were evaluated at the clinic. Of the 367 cases of biopsy-proven cervical HPV, only 33 (9%) were recorded on Papanicolaou smears performed immediately before the biopsy, and 140 (38%) also had concomitant, biopsy-proven CIN, grade II or III. Of the 195 instances in which the colposcopic impression was simple HPV without CIN, 46 (24%) had high-grade CIN on biopsy. We conclude that the proportion of patients with HPV-associated problems is increasing, that the Papanicolaou smear is not sensitive in detecting cervical HPV infections, that patients with HPV changes found on Papanicolaou smears should be evaluated with colposcopy and that lesions that appear colposcopically to be simple HPV should undergo biopsy to rule out the presence of high-grade CIN.     

TERC基因联合阴道镜及HPV检测在早期宫颈病变诊断中的应用

目的：探讨阴道镜、人端粒酶RNA组分（hTERC）基因扩增和人乳头瘤病毒（HPV）分型检测在早期宫颈病变诊断中的临床意义。方法：对经阴道镜初步诊断为宫颈病变的219例患者,应用荧光染色体原位杂交（FISH）技术检测hTERC基因扩增、表面等离子谐振技术（SPR）检测HPV感染情况,并进行统计学分析。结果：①阴道镜诊断宫颈CINⅠ级59例,CINⅡ级76例,CINⅢ级56例,宫颈癌28例,与组织学最终诊断相比较,两种方法有相关性（P＜0.05）。②hTERC基因在宫颈炎性病变、CINⅠ、CINⅡ、CINⅢ及宫颈鳞癌中的阳性扩增率分别为7.9%,10.9%,44.6%,63.2%和82.6%,各组间比较差异有统计学意义（P＜0.000 1）。③132例进行HPV分型检测的患者中,高危亚型感染54例,低危亚型感染29例,阴性49例, HPV阳性患者的感染类型同宫颈上皮内瘤变等级有关（P=0.041 9）。④同时进行hTERC基因及HPV检测患者中,54例HPV高危亚型患者hTERC基因发生异常扩增者33例,29例低危亚型中发生异常扩增7例,组间比较差异有统计学意义（P＜0.01）。结论：阴道镜作为宫颈病变的初诊手段有一定的漏诊和过度诊断;HPV高危亚型感染可能是导致hTERC基因异常扩增的因素之一;hTERC基因扩增和HPV感染与宫颈高级别病变的进展密切相关,可能是导致宫颈癌发生的直接诱因;阴道镜、HPV和hTERC基因联合检查是判断早期宫颈病变进展并做出诊断的有效手段。     

Prevalence of human papilloma virus infection of the uterine cervix in women with abnormal cervical cytology

PURPOSE OF INVESTIGATION: To determine the prevalence of human papillomavirus (HPV) using polymerase chain reaction (PCR) in women with abnormal cytology results. METHODS: A prospective study of 215 women with abnormal cytology results referred consecutively to the cervical pathology clinic was carried out. A second cervical cytology using the Bethesda System was performed on all the patients to confirm the initial diagnosis, as well as to test for the presence of HPV by PCR and a colposcopy and punch biopsy in cases presenting with an abnormal pattern on colposcopy. The sensivitiy, specificity, and positive and negative predictive value (PPV and NPV) were calculated using 2 x 2 tables. RESULTS: The women aged 35 years or younger presented a higher percentage of HPV infection (85.6%) than the women over 35 years of age (54%). The highest percentage of women with a positive result for HPV was found in those with a cytological high-grade squamous intraepithelial lesion (HSIL) (85.5%), as compared with 47.4% of the women with a cytological low-grade squamous intraepithelial lesion (LSIL). HPV infection has a high negative predictive value (93.2% of cases) and a high sensitivity (93.5%) for the detection of HSIL by biopsy, although the specificity and positive predictive value were low, 51.5% and 52.1%, respectively. CONCLUSION: Patients with cytological HSIL have a high prevalence of HPV infection.     

Prognostic factors for the development of vaginal intraepithelial neoplasia

OBJECTIVE: To identify risk factors for the appearance of vaginal intraepithelial neoplasia (VAIN). MATERIAL AND METHODS: A total of 485 women with abnormal cytologies were followed over three years (2003-2006). They underwent cytolology and colposcopy, and testing for human papillomavirus virus (HPV) infection. If the colposcopy was atypical, a biopsy was performed. RESULTS: A total of 256 women were treated: 161 by cone biopsy, 103 by LLETZ, 12 by repeat conization, and 44 by total hysterectomy. In eight cases VAIN was diagnosed following hysterectomy. The average age at which VAIN appeared was 49.8 years (age range 39-61). Hysterectomy was indicated in two cases of cervical cancer, four cases of persistent high-grade cervical SIL, and two cases of recurrent high-grade cervical SIL. The mean time for the appearance of VAIN following hysterectomy was 3.8 years (range 1-9 years). Of these eight women, seven had HPV infections at high risk for carcinogenesis. CONCLUSIONS: Long-term follow-up cytology is necessary for women treated for high-grade SIL, even after hysterectomy, because of the increased risk of a primary vaginal VAIN lesion, especially in women with high-risk HPV infection.     

Diagnosis of cervical intraepithelial neoplasia and human papillomavirus infection: punch biopsy versus cervical smear

Summary In 102 patients referred to our colposcopy clinic because of one to three Papanicolaou smears indicating cervical intraepithelial neoplasia (CIN) and/or abnormal colposcopy, routine smears and colposcopically directed punch biopsies were taken simultaneously. For detection and typing of human papillomavirus (HPV)-DNA in situ hybridization was performed in all biopsies and in 46 of the cervical smears. In cases of dysplastic lesions the number of HPV 16/18 (40.5%) and 31/33 (42.9%) was markedly higher than HPV 6/11 (16.6%) infection rate. In cases where simultaneous in situ hybridization in biopsy specimen and cervical smears was performed 21.7% showed a HPV negative smear and a positive biopsy, in 6.5% the results were the other way round. In 34.9% of cases with CIN I and 9.5% of cases with CIN II verified by punch biopsy the cytological smear did not indicate dysplasia. Our data show that mild and moderate CIN lesions of the cervix as well as HPV infection are detected more frequently by a combination of cervical smear and colposcopically directed punch biopsy than by cervical smear alone.     

Cervical screening in under 25s: a high-risk young population

OBJECTIVE: The changes to the UK NHS cervical screening programme launched in April 2004 recommend that the first cytological screening should be undertaken at the age of 25 years rather than at 20 years. This study analyses Papanicolaou smear diagnoses of women under 25 years in Lewisham Borough of London to determine the incidence of cervical intraepithelial neoplasia (CIN) in this age group. There are concerns that delaying the onset of cervical screening in this population may increase the risk of cervical cancer. STUDY DESIGN: Pap smear results of 2793 women (2617 between 20 and 24 years and 176 below 20 years) over a period of 1 year from 1 April 2003 to 31 March 2004 were analysed. Appropriate colposcopy referrals and the results of cervical biopsies performed were followed up. RESULTS: Of the 2793 cervical smears analysed: 1997 (71.5%) were normal; 375 (13.4%) inadequate; 144 (5.1%) borderline; 208 (7.4%) showed mild dyskaryosis and 69 (2.5%) showed high-grade lesions (moderate to severe dyskaryosis). One hundred and eighty-two women were referred to colposcopy: 34% showed histological evidence of high-grade precancerous lesions (CIN 2 or 3); 27% CIN 1 and 0.5% koilocytosis only. Thirteen percent had normal colposcopy while 22% did not attend. CONCLUSION: The Lewisham population of young women under the age of 25 years is vulnerable to potential precancerous cervical lesions. This may reflect a high level of sexual activity among the young girls. Absence of screening in this age group may miss these high-grade cervical lesions that could progress to cervical cancer in the near future. We reinforce the importance of cervical screening in the highly vulnerable sexually active population under 25.     

Human papillomavirus testing improves the accuracy of colposcopy in detection of cervical intraepithelial neoplasia

To assess the performance of human papillomavirus (HPV) testing and colposcopy in detection of cervical pathology. A series of 389 women referred for colposcopy due to an abnormal Pap smear had cervical swabs analyzed for oncogenic (high-risk [HR]) HPV types using Hybrid Capture II (HC2) assay. Loop electrical excision procedure cone biopsy (88%) or colposcopic biopsy (11%) was used as the gold standard. Of the atypical squamous cells of undetermined significance (ASCUS) smears, 48% were positive for HR HPV, as compared to 76.3% of low-grade squamous intraepithelial lesions (LSIL) smears. HR HPV was detected in 66.7% and 90% of patients with cervical intraepithelial neoplasia (CIN) 1 and CIN2 (or higher), respectively. The sensitivity of the Pap smear using an ASCUS threshold in detecting high-grade CIN was 94.5% (95% confidence intervals (CI): 91-97%) and that of colposcopy 98.5% (95% CI: 95-99%). The respective specificities were 30% (95% CI: 17-28%) and 35.6% (CI: 29-42%). HC2 test had comparable sensitivity, 90% (95% CI: 85-93%), but higher specificity, 54.3% (95% CI: 47-61%). Combining HC2 test with Pap increased specificity, 66.7% and 41.3% for ASCUS and LSIL cutoff, respectively. The minor-abnormality threshold together with HC2 increased specificity of colposcopy with no changes in sensitivity. High viral load (>100 relative light unit/positive control) was associated with significant disease. HPV DNA testing improves the accuracy of colposcopy in the detection of high-grade CIN in women with ASCUS or LSIL smears.     

Human papillomavirus cervical infection and associated risk factors in a region of Argentina with a high incidence of cervical carcinoma.

OBJECTIVE: To assess the prevalence and potential risk factors associated with human papillomavirus (HPV) cervical infection among women residing in a region of northeastern Argentina with a high incidence of cervical cancer. METHODS: A case-control study of 330 women participating in a cervical cytological screening program conducted in Posadas city, Misiones, Argentina, from February 1997 to November 1998 was carried out. Standardized questionnaires were administered, and clinical examination including colposcopy was performed. Fresh endocervical specimens for HPV DNA detection by generic polymerase chain reaction were collected and the products typed by dot-blot hybridization. RESULTS: Human papillomavirus DNA was found in 61% of samples analyzed (185/301). Samples with normal cytology had a 43% infection rate (85/199), while those classified as low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, and invasive cervical carcinoma had an infection rate of 96% (53/55), 100% (29/29), and 100% (18/18), respectively. Human papillomavirus typing showed a 64% (118/185) prevalence of type 16 among all the infected population analyzed; type 16 was detected among 49% (42/85) of infected samples with normal cytology and in an average of 74% (74/100) with abnormal cytology. Sexual behavior, residence in southern Paraguay, and history of a previous sexually transmitted diseases were the main risk factors associated with high-grade cervical lesions. CONCLUSIONS: An elevated prevalence of HPV infection was detected in this population, which also has a high incidence of cervical cancer. The broad distribution of high-risk HPV type 16 in women with normal cytology and colposcopy suggests that viral infection is an important determinant of regional cancer incidence.     

HPV-Infektion in der Schwangerschaft

Especially during reproductive age the prevalence of human papillomavirus (HPV) infection is high. Therefore clinical effects of a persistent HPV infection in pregnancy are commonly encountered. In this article specific suggestions for treatment of HPV infection in pregnancy are presented. All patients with abnormal cervical cytology in pregnancy should undergo a colposcopy. In case of suspected high-grade dysplasia or invasive cancer a target biopsy should be performed. In preinvasive lesions active surveillance during pregnancy is adequate without a need for surgical intervention. Therapy of invasive cervical cancer in pregnancy is an individual and interdisciplinary decision process. There is no indication for caesarean section due to Condylomata acuminata. HPV vaccination in pregnancy is not recommended, but in case of accidental vaccination no negative effects are to be expected.     

Follow-up by combined cytology and human papillomavirus testing for patients post-cone biopsy: results of a long-term follow-up

OBJECTIVE: The goal of this study was to evaluate the clinical implications of integrating human papillomavirus (HPV) testing into a long-term follow-up and management protocol for women postconization for high-grade cervical intraepithelial neoplasia (CIN2-3). METHODS: Sixty-seven women were followed-up by Pap smears and HPV type and load testing (mean follow-up, 63 months; range, 50-72). Patients with persistent abnormal cytology on two consecutive smears and those with positive HPV test results (whatever their cytologic findings) were referred for colposcopy-directed biopsy. Patients histologically diagnosed with CIN2-3 and those with high-load HPV (whatever their histologic findings) underwent repeat conization or hysterectomy for residual disease. RESULTS: At follow-up, 29 (43.2%) women had positive cytology or positive HPV results and were referred for colposcopy. Eleven (37.9%) had high-grade cervical intraepithelial neoplasia or high-load HPV results and were further treated by reconization/hysterectomy. The respective positive predictive values of high-load HPV and low-grade squamous intraepithelial lesions were 100 and 60% for any CIN and 90 and 15% for CIN2-3. Only five of nine cases with a final diagnosis of CIN2-3 were originally identified by cytology: the other four were detected only by parallel evaluation by HPV testing. High-load HPV results with normal cytology or low-grade lesions harbored an 80% risk for CIN2-3. CONCLUSIONS: Adding HPV load assessment to the follow-up protocol of women postconization due to CIN2-3 lesions could help detect high-grade residual disease among low-grade lesions and normal cytology cases while concomitantly and safely bestowing the advantage of lowering the rates of colposcopic referrals and surgical procedures.     

人乳头瘤病毒L1壳蛋白在筛查宫颈鳞状上皮内病变中的应用

目的:探讨人乳头瘤病毒(HPV)L1壳蛋白筛查HPV阳性妇女宫颈脱落细胞中宫颈鳞状上皮内病变的应用价值。方法:选取2012年5月至2014年12月就诊于温州市人民医院的妇女212例,收集宫颈脱落细胞并行HPV L1壳蛋白检测、HPV DNA分型、TCT(液基细胞学)及阴道镜下活检,比较HPV阳性妇女的宫颈脱落细胞中HPV L1壳蛋白的表达情况。结果:212例细胞学标本中HPV L1壳蛋白阳性率为33.9%,其中未见上皮内病变/恶性细胞组(NILM)、无明确诊断意义的鳞状上皮细胞病变组(ASCUS)、低度鳞状上皮内病变组(LSIL)、不能排除高度鳞状上皮内病变组(ASC-H)、高度鳞状上皮内病变组(HSIL)中阳性率分别为47.1%、35.1%、54.2%、29.2%、16.1%,各组比较差异有统计学意义(P0.05);两两比较,HSIL组与LSIL组和NILM组比较,差异均有统计学意义(P均0.005);进行数据合并后,LSIL/ASCUS组与ASC-H/HSIL组比较差异有统计学意义(P=0.001)。178例宫颈细胞学异常患者中,宫颈低级别病变和宫颈高级别病变的HPV L1壳蛋白阳性率比较,在ASCUS组(P=0.000)、LSIL组(P=0.004)中均有差异,在ASC-H组(P=0.127)、HSIL组(P=0.515)中均无差异。HPV 16/18感染患者的HPV L1壳缺失同宫颈高级别病变有更紧密的关系(P=0.003)。结论:子宫颈脱落细胞HPV L1壳蛋白检测在HPV阳性妇女的子宫颈病变筛查中具有一定的价值,可能成为一种合适的分流方法。     

Is human papillomavirus testing an effective triage method for detection of high-grade (grade 2 or 3) cervical intraepithelial neoplasia?

OBJECTIVE: Our purpose was to assess the usefulness of the polymerase chain reaction assay for detection of human papillomavirus infection for prognostic value in the triage strategies for high-grade (grade 2 or 3) cervical intraepithelial neoplasia in women referred for colposcopy after abnormal Papanicolaou smears. STUDY DESIGN: A total of 1007 women referred to a colposcopic clinic providing care for an indigent population were studied. Four hundred fifty-four women were referred after two Papanicolaou smears reported as atypical squamous cells of undetermined significance or low grade-squamous cervical intraepithelial lesion, and 553 were referred after a single smear reported as high-grade squamous intraepithelial lesion. All women had a cervical smear, colposcopy-directed biopsy, and endocervical curettage performed. A sample for human papillomavirus deoxyribonucleic acid detection by polymerase chain reaction was obtained. RESULTS: High-risk human papillomavirus types were detected in 463 (46%) of 1007 women studied. There was a significant increase of the frequency of high-risk human papillomavirus by the increasing severity of biopsy findings ranging from 32.7% in women without cervical intraepithelial neoplasia on biopsy to 60% in women having grade 2 or 3 on the biopsy specimen. Women having a negative Papanicolaou smear found to have high-risk human papillomavirus deoxyribonucleic acid at the time of colposcopy had a significantly higher rate of grade 2 or 3 cervical intraepithelial neoplasia on the biopsy specimen than did women without high-risk human papillomavirus. There was no such difference observed in women with a cytologic finding of low- or high-grade squamous intraepithelial lesions at the time of colposcopy. The polymerase chain reaction assay appears to be more sensitive than the commercial human papillomavirus profile test. The positive predictive value for grade 2 or 3 cervical intraepithelial neoplasia of both tests was similar (21.7% and 22.8%, respectively). CONCLUSION: The human papillomavirus is associated with high-grade cervical intraepithelial neoplasia, but the screening for human papillomavirus deoxyribonucleic acid does not have prognostic value in women reported as having atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesions on two precolposcopy Papanicolaou smears. (Am J Obstet Gynecol 1998;178:1235-44.)     

High-risk human papillomavirus DNA testing and high-grade cervical intraepithelial lesions

OBJECTIVE: To explore the role of high-risk human papillomavirus (HPV) DNA testing in the improvement of the recognition of cervical cancer and precancerous lesions in women with abnormal cervical cytology. METHODS: A total of 2152 women with abnormal cervical cytology were submitted to both HPV DNA testing and biopsy guided by colposcopy and the results were correlated. RESULTS: Positive rate of high-risk HPV DNA in groups of atypical squamous cells of undetermined significance (ASC-US), atypical squamous cells, cannot exclude high-grade (ASC-H), low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions was 53.7, 53.2, 84.6 and 93.0%, respectively. In each group, the detection rate of grade 2,3 cervical intraepithelial neoplasia (CIN 2,3) or cervical cancer in patients with positive HPV DNA was significantly higher than that with negative HPV DNA (P<0.05). In ASC-US group, the negative predictive value of high-risk HPV DNA testing for detection of CIN 2,3 and cervical cancer was 99.8% and the sensitivity 98%. CONCLUSION: HPV DNA testing is a useful indicator in the management of patients with ASC-US and plays an important role in the evaluation of risk for CIN 2,3 and cervical cancer.     

Human papillomavirus typing in routine cervical smears. Results from a series of 3778 patients

AIM: As human papillomavirus (HPV) infection is a significant risk factor for cervical cancer, the aim of this study was to assess the efficacy of HPV detection techniques in predicting the presence or the development of a high-grade squamous intra epithelial lesion. Additional reasons for carrying out this investigation were as follows. It was considered that the clinical value of HPV typing may have been underestimated in certain previous reports, which based their findings on first-generation assays. Moreover, until the present investigation most studies only investigated the cases with abnormal smear findings and did not include long-term follow-up, nor detailed follow-up of women with a normal smear but positive HPV typing, although this patient subgroup is of particular interest. The patient population included 3778 women who underwent routine cytological cervical screening and who gave their informed consent to participate in this study, consisting of a cervical smear, HPV testing via a second-generation Hybrid Capture II assay (which is more sensitive than first-generation tests, and can detect 18 different HPV types, i.e., 13 oncogenic and five non-oncogenic types); and in the case of abnormal smear findings, colposcopic examination and directed biopsies of the sites of suspected lesions. The women with cytomorphologically normal cervical smears but which who HPV-positive were reexamined six months later. RESULTS: HPV findings were positive in 66 cases where the initial smear indicated the presence of a high-grade lesion with the diagnosis confirmed by biopsy in 65 cases; in 155 cases (76.1%) where the initial smear indicated the presence of a low-grade lesion; in 44 (57.1%) out of 77 smears indicating the presence of ASCUS-type (atypical squamous cells of undetermined significance) lesions; and in 366 cases (10.5%) of apparently normal initial smears. After colposcopy and follow-up, a final diagnosis of high-grade lesion was made for 85 patients. All these patients were found to have high-risk (oncogene-positive) HPV at the first examination, but in only 65 cases (76.5%) was the initial smear indicative of a high-grade lesion. Finally, in the patient groups with low-grade or ASCUS-type smear findings or with an apparently normal smear, a high-grade lesion was only found in those patients with persistent high-risk HPV infection. In all, the sensitivity of the Hybrid Capture II assay in detecting high-grade lesions was 100% versus 85.9% for standard cytology. However, its specificity (86.3%) and positive predictive value were not as high as the latter. CONCLUSION: The results of this study indicate that HPV typing via this second-generation assay displays good sensitivity for the detection of at-risk cases, i.e., those involving the presence or development of high-grade cervical lesions. However, a number of issues have to be addressed before HPV typing is adopted in clinical practice, such as the fairly high HPV prevalence in women aged over 60 years, and whether the implications of this are the same as for younger age groups. Also, the present cost of complete typing remains too high for it to be used on a widespread scale. Nevertheless, HPV typing may have a useful role to play in the detection of cervical cancer.     

Relationship between human papillomavirus type 16 in the cervix and intraepithelial neoplasia

Objective: To evaluate a temporal relationship between the presence of cervical human papilloma virus (HPV) type 16 and the risk of developing cervical intraepithelial neoplasia (CIN).Methods: Fifty-four women with HPV 16 polymerase chain reaction (PCR)–positive tests were selected from the gynecologic outpatient clinic of the Reinier de Graaf Hospital, Delft, The Netherlands. At least three successive PCR tests were performed in each woman at intervals of 6 months. The PCR HPV 16 assay was performed in conjunction with cervical smear, and colposcopy and biopsy, if indicated. Women with at least three consecutive positive PCR tests were defined as having persistent HPV 16 infections. Women with one positive test followed by two negative tests were defined as having transient infections. Subdivided into two groups, 25 women had persistent infections and 29 had transient infections.Results: In significantly more women in the persistent group compared with the transient group, CIN developed (11 of 25 versus six of 29, P = .036). Lesions in women with persistent HPV 16 infection were more severe (six of 11 were CIN III versus one of six P = .041).Conclusion: Persistent infection with HPV 16 is associated with a higher risk of developing CIN, which is often high-grade.     

Cancer of the vulva in a 25-year-old woman with VIN III and high-grade cervical SIL--case report

Human papillomavirus (HPV) infection is associated with an increase in intraepithelial lesions of the genital tract which are often multicentric. Following is a presentation of a case of vulvar cancer in a young woman (25 years of age) with multiple vulvar intraepithelial neoplasia (VIN III) lesions, a high-grade squamous intraepithelial cervical lesion, and a HPV type 16 infection at high risk of oncogenic transformation. This case offers an opportunity to discuss the risk factors that may favor the appearance of these lesions in young women, and their clinical management, diagnosis, and treatment.     

Cervical cancer prevention: the impact of HPV vaccination

Cervical cancer remains a critical public health problem that is second only to breast cancer in overall disease burden for women throughout the world. In spite of the success of cervical cancer screening, Pap cytology screening is yet to be effectively implemented or has failed to reduce cervical cancer rates to an appreciable extent. Screening appears to benefit only a small fraction of women although a much larger percentage endures the inconvenience of the Pap test in order to avoid cervical cancer. The establishment of Human Papillomavirus (HPV) infection as the necessary cause of cervical precancers and cancers provides a tremendous opportunity for cervical cancer prevention through vaccination. HPV 16 and 18 which cause 70% of cervical cancers worldwide. Thus a prophylactic vaccine to prevent HPV related precancerous lesions and cancers would save lives, reduce the need for costly medical procedures and provide both women and communities throughout the world with substantial benefits. Based on the induction of neutralizing antibodies by non infectious Virus Like Particles (VLP) of L1 capside protein, prophylactic HPV vaccines have consistently induced high titter of neutralizing antibodies with minimal side effects and induce more than 90% protection from persistent HPV 16-18 infection and HPV 16 and 18 associated high-grade Cervical Intraepithelial Neoplasia (CIN) in proof of concept efficacy trials. HPV 16-18 vaccination will prevent HPV16-18 incident infection, and subsequently decrease in 90% the frequency of abnormal Pap attributable to these types and in about 50% overall abnormal Pap. HPV vaccination will reduce the number of women who require colposcopy, biopsy and cervical treatment for precancerous cervical lesions. The level of protection from death due to cervical cancer could exceed 95%. Three large phases prophylactic HPV VLP trials are now in progress and will form the basis for licensing of candidate vaccines in 2006. HPV vaccination targeting young female adolescents, aged 11 to 16 years, with a catch-up of those aged 17-25 years, would be a strategy to be addressed. Cervical cancer screening strategies, that will be cost-effective for the proper surveillance of women protected by HPV vaccination, are under analysis.     

Evaluation of HPV 16 PCR detection in self- compared with clinician-collected samples in women referred for colposcopy

OBJECTIVES: A clinical prospective evaluation study was conducted to evaluate PCR detection of high-risk human papillomavirus (HPV) type 16 in self-sampled vaginal compared with clinician-collected cervical specimens. METHODS: Paired vaginal and cervical specimens were collected from 137 consecutive women referred for colposcopy because of abnormal cervical cytology. In-house and a commercial PCR method for HPV type 16 were used. Self-sampled vaginal HPV 16 detection was compared to histology and physician-collected cervical specimens. RESULTS: Of the 137 patients, 98 had proven abnormal histology and were included in the analysis. Overall, using the cervix HPV detection as reference method, the self-sampled vaginal sample showed sensitivity 91.8%, specificity 96.1% and agreement kappa (kappa) 0.881. Using the histology as reference, all 11 cervical cancer cases were HPV-16-positive in both cervical and vaginal samples, and in 43 high-grade lesions, detection sensitivity in cervix was 72.1% (kappa 0.588) and vagina 67.4% (kappa 0.516). HPV 16 detection did not differ (P=0.27) between clinician-collected cervical and self-sampled vaginal specimens. CONCLUSIONS: The self-collected vaginal sample is highly concordant with the physician-collected cervical sample in HPV 16 detection.     

Colposcopy vs Hybrid Capture II assay in detection of cervical human papilloma virus infection

PURPOSE OF INVESTIGATION: Considering the relationship between high-risk human papillomavirus types and the presence or subsequent development of cervical high-grade preinvasive lesions, the aim of the study was to determine if the Hybrid Capture II test can be used to triage women with atypical colposcopic findings. METHODS: The study was carried out on 100 patients with suspicious colposcopy findings (suggestive of human papillomavirus infection) who underwent a cervical smear for human papillomavirus testing DNA Hybrid Capture II and direct biopsies for histopathological analysis. RESULTS: Sixteen patients were negative for human papillomavirus. Of the eight patients positive for high-risk HPV type, seven presented an abnormal transformation zone grade 2 (high-grade squamous intraepithelial lesion of the cervix at histopathology). There was a significant positivity of medium-high risk virus types in the cases with more abnormal colposcopy (chi2 = 7.44; p < 0.005). Histopathological findings of high-grade squamous intraepithelial lesions were registered in the patients positive for medium-high risk human papillomavirus types (chi2 = 7.66; p < 0.025). CONCLUSIONS: Based on these results it can be concluded that if a diagnosis of a high-grade squamous intraepithelial lesion has been made on the basis of colposcopic and histopathological findings, there is a high probability that the infection was due to one or more types of human papillomavirus. There are necessary further studies to interpretate both the advantages and disadvantages of intermediate triage procedures, like Hybrid Capture II testing, compared with immediate colposcopy.