Studies of human papillomavirus (HPV) in urological tumors

Urological tumors were examined for the presence of human papillomavirus (HPV) DNA by using Southern blot hybridization. In 20 male patients with condyloma acuminatum, HPV type 6 was found at 85% (17/20), HPV type 11 at 95% (19/20), HPV type 16 at 5% (1/20) and HPV type 18 at 0% (0/20). In 2 female patients with condyloma acuminatum, HPV types 6, 11, 16 and 18 were found at 100% (2/2), 100% (2/2), 50% (1/2) and 0% (0/2), respectively. All 6 of the patients who were positive for HPV type 6, were also positive for HPV type 11. Two patients were positive for HPV types 6, 11 and 16, the last of which was frequently found in penile cancer and uterine cervical cancer. In 6 patients with penile cancer, two patients were positive for HPV type 16 and negative for HPV types 6, 11 and 18. The remaining 4 patients were negative for all these HPV types. One patient who was positive for HPV type 16 had penile cancer after three previous episodes of penile condyloma acuminatum. From this information, a malignant change in the condyloma acuminatum was assumed to indicate the possible association of HPV type 16 with the process of malignant degeneration. HPV types, 6, 11, 16 and 18 were not detected in a female patient with vulvar cancer. Although HPV was thought to participate in the development of urological tumors except for external genital tumors, all patients examined, consisting of 2 with benign prostatic hypertrophy, 5 with prostatic cancer and 24 with bladder cancer, were negative for HPV types 6, 11, 16 and 18. Eight patients with bladder cancer were negative for HPV type 33.     

Low frequency of human papillomavirus infection in initial papillary bladder tumors

The involvement of human papillomavirus (HPV) in bladder cancer remains controversial. We previously reported detection of L1-HPV DNA in 39% of bladder cancers of mixed grade and stage. To clarify the possible etiologic role of HPV we studied, using the same technique, a more homogeneous group of initial low-stage tumors. We investigated a total of 187 newly diagnosed superficial papillary bladder tumors for the presence of L1-HPV DNA by the polymerase chain reaction method and hybridization with specific probes for HPV 6, 11, 16, 18, 33. HPV DNA was detected in 16 (8.5%) of the 187 specimens tested, although in a low copy number compared with SiHa cervical cancer cells used as control. HPV type 16 was observed in eight tumors while HPV type 6 and type 11 were each observed in three tumors. Two tumor specimens contained two types of HPV: one tumor hybridized with type 6 and 16 and the other with type 11 and 18. This low rate of HPV detection (8.5%) in initial tumors does not favor a prominent role for HPV in bladder carcinogenesis. Received: 7 September 1998 / Accepted: 7 December 1998     

Detection of human papillomavirus (HPV) DNA in human prostatic tissues by polymerase chain reaction (PCR)

Human papillomavirus (HPV) infections are strongly linked to the pathogenesis of uterine cervical neoplasms, and have been implicated in other cancers of the female genital tract. In contrast, the association of HPV with the cancers of the male urogenital tract is less evident, except in anal and penile cancers. However, recent studies reporting the prevalence of HPV infections in human prostate cancers (60–100% HPV 16 positive vs. no infection of HPV) have raised controversies regarding the prevalence of HPV in benign and neoplastic human prostate. We investigated the prevalence of HPV infections in prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinomas in 23 surgically resected prostates. Polymerase chain reaction (PCR) was used to amplify HPV 6b/11, 16 and 18 specific DNA sequences, using type specific HPV primers selected from the transforming gene E6-E7. The areas of PIN and cancer in 6 p.m H&E stained tissue sections were identified, and respective areas of PIN and cancer were isolated from the adjacent serial sections and used for DNA amplification and HPV detection (Fig. 1). Our results demonstrated the presence of HPV 16 in three carcinomas (13%), using type specific primers in PCR amplified samples. We were not able to demonstrate the presence of other HPV types (HPV 6b/11 or HPV 18) in any of the samples using specific primers. Two of these prostates showed relatively strong positive signals by dot blot analysis, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. One more sample showed weak positivity, when hybridized with a 32P-labeled HPV 16 type specific oligonucleotide probe. Subsequently, we have confirmed these results by Southern hybridization of the samples transferred to nylon membrane after agarose gel electrophoresis and detected by HPV 16 type specific oligonucleotide probe, using chemiluminescent assay. We, therefore, conclude that HPV infections of the prostate in general are not as common as has been previously claimed by other investigators. © 1993 Wiley-Liss, Inc.     

Presence of human papillomavirus DNA and abnormal p53 protein accumulation in lung carcinoma.

BACKGROUND: In some carcinomas inactivation of the tumour suppressor gene product p53, either by point mutation or indirectly by the human papillomavirus (HPV), has been suggested as two alternative routes to malignant transformation. To test this hypothesis in lung tumours, 43 lung carcinomas were analysed by in situ hybridisation and polymerase chain reaction (PCR) for the presence of HPV DNA, and the results were compared with p53 protein immunohistochemical analysis. METHODS: The presence of HPV DNA in lung carcinoma was detected by nucleic acid in situ hybridisation for HPV types 6, 11, 16, 18, 31, and 33 using nonradioactively labelled DNA probes. Polymerase chain reaction (PCR) analysis was performed on all cases showing positive HPV DNA labelling by in situ hybridisation and in an additional 13 negative cases. Abnormal nuclear accumulation of the p53 protein was revealed by immunohistochemistry using the avidin-biotin-peroxidase complex method and a CM-1 polyclonal anti-human p53 antibody and a monoclonal mutation-specific Pab 240 p53 antibody. RESULTS: HPV DNA was found by in situ hybridisation in 13 lung carcinomas (30%). In all these cases subtype-specific HPV DNA could also be detected by PCR. Abnormal p53 protein accumulation was seen in 21 of the 43 carcinomas (49%), of which 18 were HPV negative. Twelve (57%) of the CM-1 positive cases were also positive for the mutation-specific antibody Pab 240. There was an obvious inverse relationship between the presence of papilloma viral DNA and abnormal p53 protein accumulation. CONCLUSIONS: p53 plays an important part in the development of lung carcinomas and, in some cases, HPV may contribute to it by binding and inactivating the p53 protein.     

膀胱乳头状移行细胞癌中高危人乳头瘤病毒的检测

目的对高危人乳头瘤病毒（ＨＰＶ）１６、１８ＤＮＡ在膀胱癌组织中进行定位研究。方法运用地高辛标记的原位杂交技术对５２例膀胱乳头状移行细胞癌中高危ＨＰＶＤＮＡ进行检测。结果ＨＰＶＤＮＡ的阳性信号存在于肿瘤细胞核内,呈点状或点片状,其中以点状为主,约８９５％。癌旁不典型增生上皮、癌旁正常的上皮组织及Ｂｒｕｎｎ巢可同时有高危ＨＰＶ的感染,但表达呈点片状。５２例膀胱乳头状移行细胞癌中高危型ＨＰＶ１６、１８ＤＮＡ阳性１９例,阳性率为３６５％;ＰＴａＴ２期１７例,ＰＴ３Ｔ４期２例;Ｇ１,２级１４例,Ｇ３级５例。随着肿瘤分期分级的增加,ＨＰＶ１６及ＨＰＶ１８的感染率有逐渐降低的趋势,但差异无统计学意义（Ｐ＞００５）。结论病毒ＤＮＡ在膀胱癌变组织、癌旁正常及不典型增生组织中均有不同程度的表达。膀胱乳头状移行细胞癌ＨＰＶ感染率较高,浸润较浅分化较好的肿瘤更多见,提示该病毒感染可能是膀胱癌发生的早期诱因之一。     

Human papilloma virus DNA and p53 mutation analysis on bladder washes in relation to clinical outcome of bladder cancer

OBJECTIVES: High-risk human papilloma virus (HPV) types stimulate degradation and deactivation of protein associated with the p53 tumour suppressor gene via the ubiquitin-dependent pathway. For a long time, changes of the p53 tumour suppressor gene have been correlated with poor clinical outcome in patients with superficial bladder cancer. We aimed to study the association between presence of (high-risk) HPV DNA, p53 status, and clinical outcome in bladder cancer patients. This study must be seen as a preliminary study to investigate this potentially important problem. MATERIAL AND METHODS: From 107 patients, 166 bladder wash samples were obtained. p53 status was determined by mutation analysis, HPV detection, and genotyping by the SPF(10)-LiPA assay. Clinical data were abstracted from the medical files. RESULTS: The prevalence of all-type and high-risk HPV infection in malignancies of the bladder was 15.2% and 8.1%, respectively. In high-grade tumours this prevalence was 18.2% and 10.6%, respectively. In grade 1, 2 and 3 tumours the infection rate of high-risk HPV types was 0%, 3.3%, and 10.6%, respectively (trend test: p=0.221). In Ta, T1, and T2-T4 tumours the high-risk HPV infection rate was 0%, 12.5% and 18.2%, respectively (trend test: p=0.045). In the p53 wild-type patients who showed progression, 1 of 9 patients had a high-risk type HPV infection. In the group of wild-type patients who showed no progression, 4 of 37 patients had a high-risk type HPV infection (odds ratio: 1.03; 95% confidence interval, 0.1-10.5). CONCLUSIONS: The data of this pilot study show the suggestion of a positive trend in the correlation between tumour grade/stage and high-risk type HPV infection. However, no additional risk for progression is found for p53 wild-type patients with a high-risk HPV infection.     

In situ hybridization study of human papillomavirus from the penile cancer

The histochemical detection of human papillomavirus (HPV) was performed using the technique of in situ hybridization from the formalin fixed paraffin embedded specimens of penile carcinoma and condylomata+ acuminata . One of 19 penile cancer cases (5.3%) revealed the positive staining on the nuclei of the tumors for HPV type 16/18. However, the positive nuclei were scattered and localized in small part of the tumor which showed no koilocytosis. On the contrary, 11 of 12 condyloma acuminata cases (91.7%) showed positive staining on the nuclei of the tumors for HPV type 6/11, also 5 of the 11 cases (45.5%) revealed cross reaction for other type of HPV. The HPV types 6/11, 16/18 and 31/33/35 may be unrelated to the pathogenesis of the Japanese penile carcinoma. However, further study is necessary to evaluate that the number of HPV-DNA copy in our cases is too small, or the other type of HPV is responsibility.     

Human papillomaviruses 6/11, 16/18 and 31/33/51 are not associated with squamous cell carcinoma of the urinary bladder

OBJECTIVE: To assess high-risk human papillomavirus (HPV), mainly HPV type 16, 18, 31 and 33 (an important aetiological factor in squamous cell carcinoma, SCC, of the anogenital region) in SCC of the urinary bladder. MATERIAL AND METHODS: Sixteen SCC from the urinary bladder were evaluated using non-isotopic in situ hybridization with a sensitive detection system for the presence of high-risk HPV 16/18, or 31/33/51, and for HPV6/11, a low-risk type commonly found in condylomata. Previously published studies were also reviewed and assessed. RESULTS: No high-risk HPV was found in any of the SCC of the bladder evaluated. Previous reports identified nine HPV-positive SCC of a total of 105, including the present series. In four of these positive cases, HPV types were found that are considered a high risk in anogenital carcinomas. CONCLUSION: From the present and previous results, we conclude that HPV has no major role in the pathogenesis of SCC of the urinary bladder.     

膀胱癌患者阴毛毛囊人乳头瘤状病毒的检测分析

目的人类乳头瘤状病毒（human papillomavirus，HPV）与膀胱癌关系密切，HPV在膀胱癌组织中的检出率很高，但其感染途径尚不清楚，本文旨在明确膀胱癌患者阴毛毛囊HPV的感染情况。方法PCR体外扩增和DNA反向点杂交相结合的DNA芯片技术测定19例膀胱尿路上皮细胞癌患者和30例健康人阴毛毛囊HPV感染情况。结果19例膀胱尿路上皮细胞癌患者的阴毛毛囊有2例发现HPV感染，HPV感染的亚型为HPV6和HPV18，HPV的感染率为10．5％；30例健康人中2例阳性，其亚型均为HPV6，感染率为6．7％。结论膀胱尿路上皮细胞癌患者阴毛毛囊不是膀胱癌组织中HPV的感染途径（P〉0．05），推测膀胱癌组织HPV感染的途径可能为通过尿道逆行感染。     

Human papillomavirus associated with bladder cancer.

Recently published data have suggested a link between active human papillomavirus (HPV) infection and the development of bladder cancer. This study was undertaken to test for HPV genomic material in the tumors of patients without evidence of ongoing viral infection. Twenty-three consecutive patients with clinical evidence of intravesical neoplasia and no history of HPV infection or clinical evidence of intercurrent disease, underwent cystopanendoscopy and biopsy as part of the routine evaluation and treatment of their tumor. Routine pathologic evaluation and southern blot analysis of biopsy material were done to establish the presence or absence of HPV DNA in the bladder tumors. Twenty-one tumors were identified by routine histology: 20 were low-to-moderate grade transitional cell carcinomas; 1 was found to be squamous cell carcinoma; 1 patient had moderate dysplasia; and 1 patient had evidence of inflammation. Four of the 20 transitional cell tumors (20%) were found to contain HPV DNA. In addition, the patients with dysplasia and cystitis were also shown to have HPV genomic material in their biopsy specimens. Viral types 6/11, 16/18, and 31/33 were found. The 20 percent incidence of HPV genomic material in bladder tumors from patients without clinical evidence of viral infection is in keeping with the observations of other investigators. We present the implication of these findings within the context of our current understanding of viral oncogenesis in the urinary bladder.     

尿脱落细胞HPV16/18 E7基因表达对膀胱移行细胞癌诊断价值的研究

目的：探讨尿脱落细胞高危型人乳头状瘤病毒16、18E_7基因(HPV_(16/18)E_7)在膀胱移行细胞癌中的表达。方法：利用聚合酶链反应(Polymerase chain reaction,PCR)和特异性核酸内切酶技术对60例膀胱移行细胞癌患者的尿液标本进行研究。结果：膀胱移行细胞癌Ⅰ级、Ⅱ级和Ⅲ级HPV_(16)的检出率分别为73．7%、78．5%和92．3%,总的检出率为80．0%(48/60);HPV_(18)检出率分别为73．7%、71．4%和84．6%,总的检出率为75．0% (45/60)。由此可知,HPV_(16/18)的检出率差别无统计学意义(P＞0．01),但膀胱移行细胞癌Ⅲ级的检出率最高(P＜0．05)。结论：尿液中HPV_(16/18)E_7基因的检测可作为膀胱癌早期诊断的一种方法。     

Frequency of mucosal HPV DNA detection (types 6/11, 16/18, 31/35/51) in skin lesions of renal transplant patients

Human papillomaviruses (HPV) probably play a role in the development of skin cancer in renal transplant recipients. Since some mucosal HPV are strongly related to cervical cancer, we compared the frequency of HPV DNA detection (mucosal types 6/11, 16/18, and 31/33/51) in skin cancer of renal transplant recipients (21 lesions) with that in normal subjects without immunodeficiency (21 lesions) and studied the frequency of these same HPV in benign lesions of renal transplant recipients (34 lesions) and normal subjects (30 lesions). An in situ hybridization technique employing cold biotin probes was used. HPV DNA was not significantly (P = 0.095) more frequent in malignant skin cancer in renal transplant recipients (42.9 %) than in normal subjects (19.04 %), but was significantly more frequent in benign lesions in renal transplant recipients (32.4 %) than in controls (10 %; P < 0.05). These results on a limited number of skin lesions do not allow one to confirm the predominant role of mucosal HPV in the development of skin cancer in renal transplant recipients. HPV interaction with other factors related to the immunosuppressive state may play a role. Received: 21 May 1996 Received after revision: 6 September 1996 Accepted: 28 October 1996     

Anal cloacogenic and squamous carcinomas. Comparative histologic analysis using in situ hybridization for human papillomavirus DNA

In order to evaluate the morphologic and possible etiologic distinctions between anal cloacogenic and squamous carcinomas, we performed histologic examination and in situ hybridization for human papillomavirus (HPV) DNA on anal canal and anal verge carcinomas from 37 patients. Twenty-one neoplasms were invasive or in situ squamous carcinomas, 14 were invasive cloacogenic carcinomas, and two were unclassified. In situ hybridization was positive for HPV types 16/18 in 12 cases and for types 6/11 in two cases of anal squamous carcinoma (67% HPV positivity overall). All 14 cases classified as anal cloacogenic carcinoma were negative for HPV DNA by this technique. One of the two unclassified carcinomas was positive for type 16/18 DNA. We conclude that anal cloacogenic and squamous carcinomas are histologically similar but distinct neoplasms. Differential expression of HPV DNA in these lesions may be a manifestation of separate mechanisms of pathogenesis, or it may be due to varying degrees of tumor cell differentiation.     

Condylomata acuminata of the urinary bladder. Natural history, viral typing, and DNA content

Three patients with condylomata acuminata of the urinary bladder are reported. Two of the patients were immunosuppressed, and one had longstanding extensive condylomata acuminata of the external genitalia and adjacent areas. All lesions recurred at least once and were difficult to treat. The diagnosis was confirmed by in situ hybridization on archival material with human papillomavirus (HPV) DNA probes under stringent conditions. In two of the patients, probes for HPV types 6 and 11 were positive; HPV 11 only was identified in one patient. Probes for HPV types 16 and 18 and pBR322 vector controls were negative. In one patient with a strong hybridization signal, the lesion was also positive for common papillomavirus antigen. DNA content measured by cytophotometry of Feulgen-stained whole nuclei isolated from lesions in two patients revealed a markedly aneuploid DNA pattern. Whether this is a factor in the behavior of the lesions is not known at this time. Although rare, HPV infection of the urinary bladder may result in widespread condylomatosis and may mimic giant condylomas of Buschke-L?wenstein or even verrucous carcinomas, sometimes necessitating radical treatment. Nevertheless, until there is proof to the contrary, the lesions must be considered benign and should not be confused with squamous cancer of the bladder.     

Human papillomavirus-associated early vulvar neoplasia investigated by in situ hybridization

Of 21 consecutive cases of early vulvar neoplasia studied at the Istituto Nazionale Tumori of Milan, 62% appeared to be related to papillomavirus infection. This conclusion is the result of the present study by in situ hybridization with DNA probes of human papillomavirus (HPV) 6/11, 16, and 18 and of previous ultrastructural and immunohistochemical investigations. The proportion of cases associated with HPV was 78.5% for those (11/14) with histologic evidence of viral infection and 33% for those without (2/6). HPV 16 was detected in all cases that were positive by in situ hybridization except for one, which showed HPV 6/11 DNA. In one case there was a mixed triple infection for HPV 6/11, 16, and 18. The patient who was positive for HPV 6/11 had a giant condyloma associated with an inguinal lymph node containing a metastatic well-differentiated squamous cell carcinoma. Three cases were positive for papillomavirus internal capsid species-nonspecific antigen (PV-Ag) (with ultrastructural evidence of virions in one of them) and were negative for HPV-DNA hybridization. They appeared to be infected with a type of HPV not identified by the available probes. Three cases, and two sites of two other cases with double infection, were HPV-DNA-positive and PV-Ag-negative. They illustrate the limitation of immunohistochemical investigation in cases with high-grade intraepithelial neoplasia. Six cases of verrucous carcinoma of the vulva were negative for HPV DNA by in situ hybridization.     

Human papillomavirus DNA sequences in cell lines derived from head and neck squamous cell carcinomas.

There is increasing evidence that human papillomaviruses (HPV) have a casual role in some neoplasms in human beings. As examples, DNA of HPV types 16, 18, and 31 are frequently present in genital cancers in humans. Recently, oncogenic HPV types have also been identified in neoplasms of the head and neck, including verrucous carcinoma of the larynx, squamous cell carcinomas of the oral cavity and larynx, and inverted papillomas of the nose. These findings and our resource of an extensive panel of head and neck squamous cell carcinoma (HNSCC) cell lines led us to begin to investigate how frequently HPV DNA was present in these tumor cell lines. For initial analysis, twenty-two HNSCC cell lines derived from 20 patients' tumors were selected as representative of our tumor cell line panel with respect to diversity of primary site, tumor stage, patient age, sex, and clinical course. For Southern analysis, cell line DNA was tested for hybridization with DNA probes for HPV types 6, 11, 16, 18, and 31. Polymerase chain reaction (PCR) analysis was also performed on five tumor cell lines using types 6, 11, 16, 18, and 52 as probes. Southern blot analysis revealed HPV-specific signals in two of the 22 HNSCC cell lines tested. One of these, UM-SCC-23, was HPV 31 positive, which to our knowledge is the first identification of HPV 31 in HNSCC. UM-SCC-63, the other HPV-positive tumor identified by Southern analysis, hybridized with both type 18 and 31. Of the five tumor cell lines tested with PCR, two were HPV positive.(ABSTRACT TRUNCATED AT 250 WORDS)     

Association between urothelial carcinoma after renal transplantation and infection by human papillomavirus types 16 and 18

Objective

To explore the association between urothelial carcinoma following renal transplantation and infection by human papillomavirus (HPV) types 16 and 18.

Materials and Methods

Of 3780 patients who underwent renal transplantation, we identified 90 cases of urothelial carcinoma. Tumor tissues collected from the 90 renal transplant recipients were compared with those from 30 nontransplanted patients with bladder cancer (control group) for HPV types 16 and 18 using polymerase chain reactions.

Results

Seven transplanted patients were HPV positive: HPV-16 was detected in 3 patients with bladder cancer (3/90; 3.3%), and HPV-18 in 2 patients with bilateral pelvic ureteral carcinoma (2/90; 2.2%), and 2 patients with bladder cancer (2/90; 2.2%). Only 2 cases from the control group were HPV positive (both HPV-18; 2/30; 5%). The difference between the RTR and control groups was not significant (P > .05).

Conclusion

Malignant tumors in the urinary system following renal transplantation did not seems to be associated with infection by HPV-16 or -18.     

Human papillomavirus infections in laryngeal cancer

Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we review the currently known associations of HPV infections in diseases of the larynx and their potential for oncogenicity. Using several methods of detection, HPV DNA has been detected in benign (papillomatosis), indolent (verrucous carcinoma), and malignant (squamous cell carcinoma) lesions of the larynx. Consistent with the known oncogenic risk of HPV infections, common HPV types associated with laryngeal papillomatosis include low‐risk HPV types 6 and 11, with high‐risk HPV types 16 and 18 more commonly present in neoplastic lesions (verrucous carcinoma and squamous cell carcinoma). Although a broad range of prevalence has been noted in individual studies, approximately 25% of laryngeal squamous cell carcinomas harbor HPV infections on meta‐analysis, with common involvement of high‐risk HPV types 16 (highest frequency) and 18. Preliminary results suggest that these high‐risk HPV infections seem to be biologically relevant in laryngeal carcinogenesis, manifested as having viral DNA integration in the cancer cell genome and increased expression of the p16 protein. Despite this knowledge, the clinical significance of these infections and the implications on disease prevention and treatment are unclear and require further investigation. © 2010 Wiley Periodicals, Inc. Head Neck, 2011     

Laryngeal Squamous Cell Carcinoma in a 13 Year-Old Child Associated with Human Papillomaviruses 16 and 18: A Case Report and Review of the Literature

Squamous cell carcinoma (SCC) of the larynx is extremely rare in adolescents and typically has an aggressive nature. The mechanism of laryngeal oncogenesis is complex and little is known about the role that human papillomavirus (HPV) plays in SCC in adolescents. We report a case of invasive laryngeal SCC that co-expressed HPV DNA subtypes 16 and 18 in a 13 year-old boy. Detection of HPV DNA types 6, 11, 16, 18, 31, 33, and 51 was performed by in situ hybridization, with confirmation by polymerase chain reaction. Immunohistochemical staining with p16 and HPV 16/18 revealed diffusely positive staining in the tumor cells. Coinfection by HPV DNA types 16 and 18 has not been previously reported, but our case suggests that HPV is a risk factor in developing laryngeal SCC in children and adolescents. Future studies evaluating HPV in the pathogenesis of these lesions is recommended to determine its prognostic significance.     

Anti-papillomavirus vaccines and prevention of cervical cancer: progress and prospects

Human papillomaviruses (HPV) cause the development of various cutaneous and mucosal lesions. Some genotypes play a role in the genesis of cervical cancer, which is the second most common cancer in women. HPV types 16 and 18 account for 60 to 72% of all HPV-associated cervical cancers, while types 6 and 11 cause genital warts. Despite the various escape strategies viruses use to fight the natural immune system, more than 90% of the infections clear spontaneously. It should therefore be possible to prepare prophylactic vaccines. The HPV major capsid protein L1 self-assembles into virus-like particles (VLP). Immunization after parenteral vaccination with it provided very good protection against experimental infection in different animal models. The first clinical trials revealed the satisfactory tolerance and excellent immunogenicity of these vaccines. Two vaccine approaches were selected: one based on protection against cervical cancer from a bivalent VLP L1 vaccine containing the two genotypes most frequently involved in cervical cancer (type 16 and 18) and the other, protecting against warts as well as cervical cancer, with a quadrivalent HPV VLP L1 vaccine containing genotypes 6, 11, 16 and 18. Initial results with these vaccines show an efficacy of more than 90% against infection and 100% against the onset of dysplastic lesions. Despite these hopeful results, a vaccined strategy sould still be defined. Meanwhile, the cytology screening program should be carried on until the beginning of the vaccination.