Molecular and serological studies of human papillomavirus among patients with anal epidermoid carcinoma

Certain types of human papillomavirus (HPV) are associated with anogenital carcinomas, including carcinomas of the anal canal. Whereas several serological studies have found an association between papillomavirus antibody responses and cervical carcinoma, the antibody response against papillomavirus antigens among patients with anal carcinoma has not been investigated. The present study has examined the antibody responses to a panel of papillomavirus-derived antigens and compared the serological profile with the histology and HPV carrier state of the tumor, as well as with the stage and prognosis of the disease. Sera from 64 patients with anal cancer and from 79 healthy blood donors were studied in ELISA for the presence of IgA and IgG antibodies to 5 previously described HPV16-derived synthetic peptide antigens. Serum IgA antibodies to a peptide antigen derived from the E2 region of HPV16 were found in 89% of patients with anal cancer as compared to 24% of controls (p = 0.0001). The IgA reactivity to the 4 other antigens showed only low and non-significant increases in mean titer. Serum IgG responses were similar among patients and controls. Among patients who had progressive disease, 21/21 were seropositive for IgA anti-E2 at diagnosis, as compared to 36/43 patients who were in remission after a mean follow-up of 41 months (p = 0.05). Forty-seven cases of anal carcinoma were also studied for the presence of HPV by in situ hybridization using a probe mix of 7 anogenital HPV types. Sixteen patients (35%) carried HPV in their anal cancer and one patient had an HPV-positive benign lesion adjacent to the tumor. Patients with HPV-carrying anal cancer were significantly younger than those with HPV-negative anal cancers (mean age: 57 and 68 years, respectively, p = 0.03). No differences in seroreactivity or HPV carrier state were seen depending on the stage or histological type of the tumor.     

1975-1995 Revised anti-cancer serological response: Biological significance and clinical implications

In the 1970s a considerable amount of work was carried out inan attempt to identify an anti-tumor serological response incancer patients. These analyses have not been very informativedue to the complexity and heterogeneity of the response. Morerecently, the availability of recombinant molecules, syntheticpeptides and analytic and semi-quantitative assays has enableda better dissection of humoral immunity. Antibodies againstintracellular antigens (c-myb, c-myc, p53 and p21 ras) havebeen found in a significant, albeit varying, proportion of patientsbearing various tumors. Association with a poor prognosis isdocumented for anti-p53 antibodies in breast carcinoma patients.A number of cell surface anti gens, including mucins, oncoproteinsand carbohydrate antigens have been found to elicit a humoralimmune response and, in some instances, circulating immune complexeswere observed. A protective role for or, on the other hand,masking effects of such antibodies is still controversial. An indication that a serological response can be beneficialcomes from vaccination studies. A significant association betweenthe development of an anti-tumor antigen antibody response andprolonged survival was observed following vaccination of melanomapatients with GM2 or anti-idiotypic antibodies which molecularlymimic tumor-associated antigens. It is to be hoped that in thenear future the numerous ongoing immunization trials and prognosticstudies demonstrate whether antibody response can exert a protectiverole in vivo. prognosis, serological response, TAA, therapy, vaccination     

Antibodies against linear and conformational epitopes of human papillomavirus type 16 that independently associate with incident cervical cancer

In a seroepidemiological study of incident cervical cancer, 94 cases and 188 population-based controls were used to evaluate the disease-association of IgG and IgA antibody responses against 6 human papillomavirus (HPV) type-16 antigens. Nine of the tested antibody responses were positively associated with cervical cancer, with odds ratios (ORs) ranging from 2.5 to 15.0. The antibody responses most strongly associated with cervical cancer were IgA against E6:10, an epitope derived from the carboxyterminal part of the HPV16 E6 [OR = 15.0, confidence intervals (CI) = 5.9–48.6], IgG against HPV16 virus-like particles (OR = 9.5, CI = 3.9-28.0) and IgG against the EI:19 epitope in the middle part of the EI protein of HPV16 (OR = 7.7, CI = 3.9–16.5). When the 3 serological assays that showed the strongest association with cervical cancer were combined, positivity for 2 assays was found among 52% of cases at an OR of 29.9. We conclude that antibody responses to several linear and conformational HPV epitopes are independently associated with cervical cancer and that combined analysis of several HPV antibody responses can result in better predictive values for HPV-associated cancer. © 1995 Wiley-Liss, Inc.     

Markers of HPV infection and survival in patients with head and neck tumors

The purpose of this study was to determine whether changes in human papillomavirus (HPV) DNA prevalence in oral rinses and/or HPV‐specific antibody levels in the sera of patients with oral/oropharyngeal cancer have prognostic significance. One hundred and forty‐two patients with oral/oropharyngeal tumors were enrolled. The presence of HPV DNA was assayed in tumor tissue and oral rinses and HPV‐specific antibodies were assessed in the sera. Oral rinses were collected before treatment and one year after the treatment. Sera were drawn before treatment, one month, and one year after the end of the treatment. Altogether, 59.2% of tumors were HPV positive. The presence of HPV DNA in the tumors correlated with HPV DNA positivity in oral rinses and with HPV‐specific antibodies in the sera. Out of 66 patients with HPV‐positive oral rinses at enrolment, 84.8% became negative at one‐year follow‐up, while most patients remained seropositive for HPV‐specific antigens. However, the mean titers of HPV16 E6 and/or E7 antibodies at follow‐up were significantly lower. Of 16 patients with recurrences at follow‐up (alive on second sampling), six were positive at enrolment for HPV16 E6 and/or E7 antibodies. In five of these, no decrease in antibody levels was observed. Titers of antibodies specific for HPV16 capsid antigens did not change during the follow‐up. Our data suggest that the detection of antibodies specific for the HPV 16 E6 and E7 oncoproteins may serve not only as a marker of HPV etiology, but also as a marker of recurrence and a prognostic indicator in patients with HPV‐positive tumors.     

Vaccines against human papillomavirus and cervical cancer: promises and challenges

Cervical cancer and precancerous lesions of the genital tract are major threats to the health of women worldwide. The introduction of screening tests to detect cervical cancer precursor lesions has reduced cervical cancer rates in the developed world, but not in developing countries. Human papillomavirus (HPV) is the primary etiologic agent of cervical cancer and dysplasia. Thus, cervical cancer and other HPV-associated malignancies might be prevented or treated by HPV vaccines. Two vaccine strategies have been developed. First, prevention of HPV infection through induction of capsid-specific neutralizing antibodies has been studied in clinical trials. However, because the capsid proteins are not expressed at detectable levels by infected basal keratinocytes or in HPV-transformed cells, a second approach of developing therapeutic vaccines by targeting nonstructural early viral antigens has also been developed. Because two HPV oncogenic proteins, E6 and E7, are critical to the induction and maintenance of cellular transformation and are coexpressed in the majority of HPV-containing carcinomas, most therapeutic vaccines target one or both of these gene products. A variety of approaches is being tested in therapeutic vaccine clinical trials, whereby E6 and/or E7 are administered in live vectors, as peptides or protein, in nucleic acid form, or in cell-based vaccines. The paradigm of preventing HPV infection through vaccination has been tested, and two vaccines are currently in phase III clinical trials. However, current therapeutic vaccine trials are less mature with respect to disease clearance. A number of approaches have shown significant therapeutic benefit in preclinical papillomavirus models and await testing in patient populations to determine the most effective curative strategy.     

Serological response to HPV16 in CIN-III and cervical-cancer patients. Case-control studies in Spain and Colombia

This study evaluates the association of antibodies against HPV-16-derived peptides with cervical cancer and estimates the sensitivity and specificity of the serological assays in relation to HPV DNA detection in cervical cells by PCR. Study subjects were derived from 4 case-control studies carried out in Spain and Colombia. Sera from 544 cases of CIN III and invasive cancer and of 543 age-matched controls were tested for antibodies to 5 peptides derived from E2, E7 (3 partially overlapping frames of HPV 16 denoted E7/1, E7/2, E7/3) and L2 open reading frames of HPV 16. HPV DNA was detected using a LI-PCR based method. Among cancer controls, antibody response to E2 and E7/1, E7/2, E7/3 was higher in Colombia (22.5%, 7.2%, 11.7%, 12.6% respectively) than in Spain (17.1%, 4.7%, 5.9%, 5.9%). E7 antibodies were related to stage, particularly in CIN III vs. invasive stages and less markedly within invasive stages. Detection of antibodies to the E7/1 was associated to CIN III (OR = 1.8). The risk of invasive cervical cancer was increased among those with antibodies to E2 (OR = 2.2), to E7/1 (OR = 4.2), to E7/2 (OR = 4.3), and to E7/3 (OR =2.5). Presence of antibodies to all the 3 E7 peptides increased the risk of CIN III (OR = 5.6) and that of invasive cancer (OR = 17.5). High levels of antibodies to E7/1 or E7/2 or E7/3 increased the risk of invasive cervical cancer (OR for high levels of antibodies vs. negatives to E7/1 OR = 22.6; E7/2 OR = 7.5, E7/3 OR = 3.4). In the present analysis, antibodies to L2 were not associated with either CIN III or cervical cancer. Serological markers of HPV 16 detected less than half of the HPV-16-DNA-positive cases. It is concluded that antibodies to E2 and particularly E7 antigens are strongly associated with cervical cancer. Antibodies to E7 seem to be a moderate marker of tumor burden. © 1996 Wiley-Liss, Inc.     

Monoclonal antibodies from mice bearing human colorectal carcinoma xenografts

We have examined the serological response in immunosuppressed mice bearing xenografts of the human colorectal carcinoma line HT29. The sera of such animals contain antibodies which bind to HT29 cell membrane components. This antibody activity was not completely absorbed by either human lymphocytes or red blood cells suggesting that at least part of this activity is directed against tumour-associated antigens. By fusing the spleens from tumour-bearing animals to an established myeloma line we were able to produce 34 monoclonal antibodies which bound to HT29 cells. The specificity of these antibodies in binding assays against membrane preparations from a variety of normal and malignant tissues and cell lines was determined. Twenty-seven bound to components present on both normal and malignant human cell membranes; 4 to tumour membranes only, whilst 3 bound specifically to membranes prepared from colorectal carcinoma tissue or cell lines. Thus despite immunosuppression the xenograft-bearing mouse was able to recognise a number of antigens present on the tumour surface.     

Antibodies against oncoproteins E6 and E7 of human papillomavirus types 16 and 18 in patients with head-and-neck squamous-cell carcinoma

Human papillomaviruses (HPVs) have been recognized as an essential pathogenic factor in anogenital cancer. HPV DNA has also been found in a subgroup of head-and-neck squamous-cell carcinomas (HNSCCs), and a causative role of the virus in the development of these tumors has been suggested by the concomitant inactivation of the tumor-suppressor protein pRb. Using 4 second-generation ELISAs, we found antibodies against at least 1 of the oncoproteins E6 and E7 of the high-risk HPV types 16 and 18 in 11 of 92 sera (12%) taken from HNSCC patients at or near diagnosis, in 1 of 52 sera (2%) taken from HNSCC patients >6 months after diagnosis and in 10 of 288 sera (3. 5%) taken from sex- and age-matched healthy control individuals of the normal population. In 11 of the 12 seropositive HNSCC cases, antibodies were directed against HPV16 proteins. In patients, the HPV16 antibodies were mostly of high titer, and in 6 cases, antibodies against both HPV16 oncoproteins were present. Seven of the 8 HPV16 antibody-positive sera from the control group were of low titer, and none of the 10 antibody-positive sera reacted with both oncoproteins of the same HPV type. The HPV type of the antigens detected by the antibodies in HNSCC patients correlated well with that of the HPV DNA found in the tumor. Of 19 patients known to have HPV16 DNA-positive tumors, 7 (37%) also had HPV16 E6 and/or E7 antibodies. Our finding suggests that the antibodies were formed in an immune response against HPV E6 and E7 proteins expressed in the HNSCC and thus strongly supports the concept of a biologically active role of HPV in the development of a subgroup of HNSCC.     

High-risk human papillomavirus is sexually transmitted: evidence from a follow-up study of virgins starting sexual activity (intercourse).

Genital human papillomavirus (HPV) infection is generally considered to be sexually transmitted. However, nonsexual spread of the virus has also been suggested. The goal of this study was to assess: (a) the role of sexual intercourse in the transmission of HPV; (b) the determinants for seroconversion; and (c) the correlation between HPV DNA, abnormal cervical cytology, and serological response to HPV16. One hundred virgins and 105 monogamous women were randomly selected from a population-based cohort study in Copenhagen, Denmark, in which the women were examined twice with 2-year interval (interview, cervical swabs, Pap smear, blood samples). The presence of HPV DNA was determined by GP5+/6+ primers based HPV-PCR-EIA. HPV 16 virus-like particles (VLP) antibodies were detected by ELISA. All of the virgins were both HPV DNA negative and seronegative to VLP16, except for one woman who was weakly HPV 6 DNA positive. Only those virgins who initiated sexual activity became HPV DNA positive and/or VLP16 positive. The most important determinant of HPV DNA acquisition was the number of partners between the two examinations. The only significant risk factor for HPV 16 VLP seroconversion among women acquiring HPV DNA was HPV type. Our results show that sexual intercourse is important in the transmission of HPV, and that HPV 16 VLP seroconversion and the development of cervical lesions only occur after HPV transmission. Remarkably, no cervical lesions were found in HPV 16 DNA positive women who had seroconverted. Although based on small numbers, this may suggest that the development of antibodies had a protective effect.     

Multiple imputation and clinico-serological models to predict human papillomavirus status in oropharyngeal carcinoma: An alternative when tissue is unavailable

In cancer epidemiological studies, determination of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) typically depends on the availability of tumor tissue testing, and/or tumor tissue access. Identifying alternative methods for estimating HPV status can improve the quality of such studies when tissue is unavailable. We developed multiple predictive models for tumor HPV status and prognosis by combining both clinico-epidemiological variables and either serological multiplex assays of HPV or multiple imputation of HPV status (HPV_mi). Sensitivity, specificity and accuracy of these methods compared to either p16 immunostaining (p16 IHC) or survival were assessed. When compared to a reference of tumor tissue p16 IHC in 783 OPSCC patients, the clinic-HPV_sero model incorporating a composite of 20 HPV serological antibodies (HPV_sero) and 4 clinical factors (c-index: 0.96) performed better than using HPV_sero (c-index: 0.92) or HPV_mi (c-index: 0.76) alone. However, the model that contained a single HPV16 E6 antibody combined with four clinical variables, performed extremely well (clinic-s1-16E6; c-index: 0.95). When defining HPV status by HPV_sero, s1-16E6, HPV_mi or through p16 IHC, each of these definitions demonstrated improved overall and disease-free survival in HPV-positive OPSCC patients, when compared to HPV-negative patients (adjusted hazard ratios between 0.25 and 0.63). Our study demonstrates that when blood samples are available, a model that utilizes a single s1-16E6 antibody combined with several clinical features has excellent test performance characteristics to estimate HPV status and prognosis. When neither blood nor tumor tissue is available, multiple imputation, calibrated on local population characteristics, remains a viable, but suboptimal option.     

Antibodies against oncoproteins E6 and E7 of human papillomavirus types 16 and 18 in cervical-carcinoma patients from Russia

Certain human papillomaviruses (HPV), mainly types 16 and 18, have been widely recognized as an essential etiologic factor for the development of carcinoma of the uterine cervix. The early HPV proteins E6 and E7 are consistently expressed in the tumor cells, and cervical-carcinoma patients can develop antibodies against these oncoproteins. For cervical-carcinoma patients from Eastern Europe and Russia, detailed information on HPV DNA prevalence and HPV-specific immune responses is limited. The presence of HPV DNA in 128 Russian cervical-carcinoma tissues was determined: HPV16 DNA was found in 78% of the cases, HPV18 DNA in 14%, and no HPV-DNA in 10%. Using 4 recently developed sensitive and highly specific second-generation enzyme-linked immunosorbent assays, we also analyzed the prevalence of antibodies against HPV16 and -18 E6 and E7 proteins in sera from 95 cervical-carcinoma patients, from 61 female patients with non-HPV-associated tumors and from 83 female healthy controls. The strong association of E6 and/or E7 antibodies with cervical carcinoma was confirmed, with 36% seropositives in this group against only 2% in the control groups. The detected antibodies are highly HPV-type-specific since all 26 HPV16-E6- or -E7-antibody-positive patients had HPV16 DNA in their tumor and 6 out of the 8 HPV18-antibody-positive patients had HPV18 DNA. Antibody responses to HPV16 E6 and E7 appear to be dependent on clinical stage of the disease, with 21% seropositives found in FIGO stage I, 42% in stage II and 53% in stage III. Antibody response to HPV16 E6 is more frequent than to E7, especially in early stages.     

Mapping of linear epitopes of human papillomavirus type 16: the L1 and L2 open reading frames.

Certain types of human papillomavirus (HPV), notably HPV type 16, are associated with flat or inverted proliferative lesions of the cervix uteri that can progress to malignancy. As a first step towards the serological study of the epidemiology of HPV, we have synthesized the entire amino acid sequences of the 2 major viral capsid proteins of HPV type 16, L1 and L2, as a set of 66 synthetic 20-residue peptides with an overlap of 5 amino acids. The peptides were tested for reactivity with IgA, IgG and IgM antibodies in the sera of 30 patients with HPV-16-carrying cervical neoplasms. Both IgG and IgM antibody responses were detected, but most of the reactivity found was of the IgA class. The most immunoreactive peptides were further analyzed for reactivity with sera from 22 patients with parotid gland tumors and with sera from 38 healthy individuals. The L2-encoded protein contained only one major linear epitope, which was not specific for HPV-16-carrying neoplasms. In contrast, the L1-encoded protein contained several epitopes that were regularly immunoreactive with antibodies present in the sera of patients with HPV-16-carrying cervical neoplasms, but only rarely so in the sera of patients with other tumors or of healthy individuals.     

The distribution of human papillomavirus in tissues from patients with head and neck squamous cell carcinoma

Several types of HPVs have been shown to be associated with the development of malignant cancers in various head and neck tumors. More information on the HPV prevalence in patients with head and neck squamous cell carcinomas (SCCs) need to be obtained. In this study, formalin-fixed and paraffin-embedded tissues of 93 pathologically diagnosed head and neck SCC patients were collected from Peking University Cancer Hospital. HPV DNA sequences in tumor tissues were screened by a commercial Luminex technique for HPVs and HPV-specific PCR assays. Presence of HPV16/18 oncoprotein in tumor tissues was assessed by immunohistochemistry (IHC) with HPV16/18 E6-specific antibodies. Of the 93 patients, 16?(17.2%) cases were found to be HPV DNA-positive, including 7 HPV18-positive, 8 HPV16-positive and 1 HPV52-positive. IHC assays demonstrated that 31.2% (29/93) tested sections showed positive signals in the tumor cells. The total positive rate of HPV genome and its encoding products in the tested samples was 44.1% (41/93). Further analyses revealed that HPV infections in head and neck SCCs were significantly related with the tumor anatomic sites, showing decreasing tendency from outside (lip cancer) to inside (laryngeal cancer), but had no correlation with pathological, clinical grades and age of the patients. In all, HPV infections are commonly identified in the tumor tissues of patients with head and neck SCCs, in which HPV16 and 18 are the most prevalent HPV genotypes. Direct detection of high-risk HPV oncoprotein by IHC may be a good tool for classifying a tumor as truly HPV-associated.     

Safety and immunogenicity of TA-HPV, a recombinant vaccinia virus expressing modified human papillomavirus (HPV)-16 and HPV-18 E6 and E7 genes, in women with progressive cervical cancer.

PURPOSE: Cervical cancer, the second most common malignancy in women worldwide, is almost invariably associated with infection by human papillomavirus (HPV). HPV-16 or -18 is commonly present in 70% of cervical cancers. HPV-positive tumor cells present antigens of the viral protein in the context of human leukocyte antigen (HLA) class I that can be recognized by CTLs. We have conducted a study in patients with early-stage cervical cancer to assess the safety and immunological effects of vaccination with TA-HPV, a live recombinant vaccinia virus expressing modified forms of the HPV-16 and -18 E6 and E7 proteins. EXPERIMENTAL DESIGN: Twenty-nine patients with clinical International Federation of Gynecologists and Obstetricians (FIGO) stage Ib or IIa cervical cancer were given two vaccinations with TA-HPV at least 4 weeks apart, starting 2 weeks before radical hysterectomy. Patients were monitored closely for side effects of the vaccination. Serial blood samples were examined for HPV-specific CTLs or changes in levels of antibodies to HPV-16 or -18 E6 and E7 proteins and to vaccinia virus. RESULTS: Vaccination with recombinant vaccinia was well tolerated in all patients with only mild to moderate local toxicity, and no serious adverse events were attributable to the vaccine. After a single vaccination, HPV-specific CTLs were found in four patients (HLA A1, A3, three patients; HLA A1, A24, one patient). Eight patients developed HPV-specific serological responses. CONCLUSIONS: This study confirmed the safety and immunogenicity of the vaccine in a proportion of those patients vaccinated. Additional clinical studies using TA-HPV in combination with an additional experimental vaccine for HPV-16 are currently under way.     

Human papillomavirus (HPV) type 16-specific CD8+ T cell responses in women with high grade vulvar intraepithelial neoplasia

Human papillomavirus (HPV)-associated vulvar intraepithelial neoplasia (VIN) has serious sequelae for the sufferer. Current treatments are associated with poor response and high relapse rates. The development of HPV-specific T cell immunotherapies offers a new approach to treatment. This will require a detailed understanding of the spectrum of T cell responses induced by HPV antigens, and how effectively viral antigens can be accessed by the immune system. We have investigated the frequency and spectrum of HPV16-specific CD8+ T cell responses to three HPV16 antigens in 9 women with high grade VIN (VIN3). CD4-depleted populations of responder cells were screened against overlapping 30-35mer peptides covering the sequences of HPV16 E6, E7 and E4 using ELISPOT assays of IFN-gamma release. We demonstrated CD8+ T cell reactivity to one or more of the proteins in 6 of 9 patient samples. All 6 of these responders recognised peptides covering the E7 protein, 3 of 9 women responded to E6 peptides, but no reactivity was seen to E4. Our results suggest that HPV16-specific cytotoxic T cells (CTLs) are relatively common in women with persistent VIN3. The HPV-specific CTL response, however, seems to be ineffective. There is some evidence that there are problems associated with the processing and presentation of HPV antigens by the infected vulvar epithelium. It will be crucial to address this in the design of any T cell based therapy for HPV-associated VIN and vulval cancer.     

Patterns of antibody responses to nonviral cancer antigens in head and neck squamous cell carcinoma patients differ by human papillomavirus status

There have been hints that nonviral cancer antigens are differentially expressed in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC). Antibody responses (AR) to cancer antigens may be used to indirectly determine cancer antigen expression in the tumor using a noninvasive and tissue-saving liquid biopsy. Here, we set out to characterize AR to a panel of nonviral cancer antigens in HPV-positive and HPV-negative HNSCC patients. A fluorescent microbead multiplex serology to 29 cancer antigens (16 cancer-testis antigens, 5 cancer-retina antigens and 8 oncogenes) and 29 HPV-antigens was performed in 382 HNSCC patients from five independent cohorts (153 HPV-positive and 209 HPV-negative). AR to any of the cancer antigens were found in 272/382 patients (72%). The ten most frequent AR were CT47, cTAGE5a, c-myc, LAGE-1, MAGE-A1, -A3, -A4, NY-ESO-1, SpanX-a1 and p53. AR to MAGE-A3, MAGE-A9 and p53 were found at significantly different prevalences by HPV status. An analysis of AR mean fluorescent intensity values uncovered remarkably different AR clusters by HPV status. To identify optimal antigen selections covering a maximum of patients with ≤ 10 AR, multiobjective optimization revealed distinct antigen selections by HPV status. We identified that AR to nonviral antigens differ by HPV status indicating differential antigen expression. Multiplex serology may be used to characterize antigen expression using serum or plasma as a tissue-sparing liquid biopsy. Cancer antigen panels should address the distinct antigen repertoire of HPV-positive and HPV-negative HNSCC.     

Prevalence of antibodies to human papillomaviruses in the general population of the Czech Republic

Sera from 450 individuals between the age of 1 and 80 years, representing the general population of the Czech Republic, were tested for the presence of antibodies to human-papillomavirus(HPV)-derived antigens. The following antigens were used: (i) HPV1 virions; (ii) HPV16, -18 and -33-virus-like particles (VLP); (iii) peptides derived from L2 open reading frames (ORFs) of HPV16 and HPV6/11; (iv) peptides derived from HPV16 E2, E4 and E7 ORFs of HPV16. The prevalence of antibodies reactive with the capsid-derived antigens was age-dependent, while no clear age dependence was observed in the distribution of antibodies to peptides derived from HPV16 early proteins. In individual sera, high correlations between the presence of antibodies reactive with the 2 L2 peptides, also between the antibodies reactive with different VLPs, were found. While the simultaneous presence of the 2 L2 antibodies was frequently detected in individual sera in all age groups, the simultaneous occurrence of VLP antibodies was detected mostly in subjects older than 20 years. There were no significant differences in HPV-antibody distribution between men and women. Int. J. Cancer 77:689–694, 1998. © 1998 Wiley-Liss, Inc.     

Use of monoclonal antibodies in the treatment of cancer of the pancreas: towards new progress?

Pancreatic cancers rank amongst the most deadly malignant diseases with a 5 year-survival percentage less than 2% and few therapeutic approaches are hitherto available. This study presents the recent attempts to construct antibodies for therapy. The characterization of pancreatic tumor-associated antigens which might serve as target antigens for antibody therapy is the limiting factor before considering the treatment of pancreatic cancer with antibodies. Antigens such as CA 19-9, BW 494 and DU-PAN-2 have been reported to be associated with pancreatic cancers. However, monoclonal antibodies directed to these antigens was not proven to be specific enough to warrant therapeutic utilization and new tumor-associated antigens must be identified. Remarkable progress has been made recently in the construction of antibodies for therapy. Amongst these antibodies are "chimeric" antibodies, antibody heteroconjugates or hybrid antibodies. The in vivo utilization of those antibodies may well result in effective tumor-cell destruction.