Human papillomavirus DNA in glandular dysplasia and microglandular hyperplasia: presumed precursors of adenocarcinoma of the uterine cervix

Presumed precursors of adenocarcinoma of the uterine cervix were investigated with specific techniques to identify human papillomavirus (HPV) DNA. The presence of HPV DNA in 36 lesions of glandular dysplasia and 16 lesions of microglandular hyperplasia of the uterine cervix was studied by in situ hybridization using 3H-labeled HPV 16 and HPV 18 DNA probes. Only two of 36 lesions (6%) of glandular dysplasia contained HPV 18 DNA, although 64% of coexisting adenocarcinoma in situ, microinvasive adenocarcinoma, and cervical squamous intraepithelial neoplasia III lesions contained HPV 18 and/or HPV 16 DNA. Two lesions of HPV 18 DNA-positive glandular dysplasia coexisted with adenocarcinoma in situ that contained the same type of HPV DNA. None of the microglandular hyperplasia lesions contained HPV 16 DNA or HPV 18 DNA. These results suggest that, if HPV infection is an initial step toward carcinogenesis, it is unlikely that glandular dysplasia and microglandular hyperplasia are precursor lesions of adenocarcinoma of the uterine cervix. A large proportion of glandular dysplasia may represent reactive lesions of endocervical columnar epithelium. Two lesions of HPV 18 DNA-positive glandular dysplasia may represent well-differentiated components of adenocarcinoma in situ of the uterine cervix.     

Human papillomavirus messenger RNA expression in adenocarcinoma in situ of the uterine cervix

Over recent years, the association between human papillomavirus (HPV) and squamous cell carcinoma of the cervix and its precursors has been well established, largely as a result of advances in the techniques of molecular biology. A similar association between HPV and invasive adenocarcinoma of the cervix has also been recently demonstrated; however, little work has been published on the relationship between the precursor lesion, adenocarcinoma in situ (ACIS), and HPV. We have therefore undertaken an in situ hybridization study of 22 cases of known cervical ACIS using probes for HPV messenger RNA expression. Seventeen of these had residual ACIS in the blocks studied, 15 of which (88.6%) expressed HPV messenger RNA. Five cases were positive for HPV 16 and 10 cases for HPV 18. Early invasive adenocarcinoma was present with ACIS in three cases and one case had early invasion plus cervical intraepithelial neoplasia (CIN III). These invasive lesions showed a similar type and degree of HPV expression as the in situ component. One section had only residual CIN III, which was positive for HPV type 18. Four cases had only minor glandular atypias (less than ACIS) in the studied sections, and all four of these were negative for HPV expression. None of the normal endocervical epithelia in any of the sections were positive by this technique. In summary, the finding of HPV messenger RNA expression in nearly 90% of cervical ACIS supports a possible role for these viruses in the pathogenesis of glandular neoplasms of the uterine cervix.     

In situ hybridization study on the detection of HPV DNA in adenocarcinoma and adenosquamous carcinoma of the uterine cervix]

Human papillomavirus (HPV) types 16 and 18 have been found closely associated with squamous cell carcinoma and related lesions of the uterine cervix. In order to investigate the relationship between HPV and adenocarcinoma and adenosquamous carcinoma of the uterine cervix, formalin-fixed, paraffinembedded tissues prepared from 38 cases consisting of 30 cases of adenocarcinoma and 8 cases of adenosquamous carcinoma were examined for the presence of HPV DNA by in situ hybridization with digoxigenin labeled HPV 6/11, 16, 18 DNA probes. HPV DNA was localized on the nuclei of the cancer cells in adenocarcinoma and adenosquamous carcinoma. HPV DNA was detected in 13 cases (43.3%) of adenocarcinoma and 4 cases (50.0%) of adenosquamous carcinoma, and HPV type 18 DNA was detected in 13 cases (34.2%) of adenocarcinoma and adenosquamous carcinoma. These findings suggest an association between HPV, especially HPV type 18, and adenocarcinoma and adenosquamous carcinoma of the uterine cervix.     

Prevalence of human papillomavirus types 16 and 18 in cervical adenocarcinoma and its precursors in Scottish patients

Our aim was to determine the prevalence of human papillomavirus (HPV) types 16 and 18 in cervical adenocarcinoma (and its precursors) in Scottish patients. Nucleic acid was extracted from paraffin-embedded, formalin-fixed tissues. We examined 119 cases of invasive adenocarcinoma, 20 cases of adenocarcinoma in situ, and 16 cases of normal glandular epithelium. HPV DNA was detected by polymerase chain reaction using type-specific primers for the E6 and E7 genes of HPV-16 and HPV-18 with conformation of HPV genotype by subsequent restriction fragment length polymorphism. HPV DNA was identified in 87 (62.6%) cases, with HPV-16 being detectable in 65 (47%) cases and HPV-18 in 41 (29%) cases. All the cases of normal tissue tested negative for HPV-16 and/or HPV-18. No significant relation between infecting HPV type (16 or 18) and subtypes of disease (within the invasive category and between the preinvasive and the invasive categories) was noted. Our findings support that HPV-16, along with HPV-18, are likely to play a significant role in the pathogenesis of cervical adenocarcinomas and that cervical cancer screening strategies that incorporate oncogenic HPV testing, and prophylactic vaccines that target these types, will be beneficial for the reduction of adenocarcinoma and associated glandular precursors.     

Symposium part I: adenocarcinoma in situ, glandular dysplasia, and early invasive adenocarcinoma of the uterine cervix.

A relative and an absolute increase in the incidence of adenocarcinoma of the uterine cervix has occurred in the United States since 1970. Currently, most pathologists recognize the histologic and cytologic features of invasive adenocarcinoma of the cervix, but there is confusion surrounding the histologic features and biologic behavior of adenocarcinoma in situ, endocervical glandular dysplasia, and the definition of microinvasive adenocarcinoma of the cervix. Similarly, the distinction of in situ adenocarcinoma from an early invasive adenocarcinoma of the cervix may be problematic. This article focuses on the histologic criteria, biologic behavior, and some approaches to therapy for these challenging lesions. General conclusions based largely on published studies include the following: 1) adenocarcinoma in situ (AIS) is a recognizable precursor to invasive adenocarcinoma and can be divided according to distinct histologic subtypes; 2) AIS is multifocal or involves multiple quadrants of the cervix in about half of cases; 3) AIS can be cured by simple hysterectomy and in many cases may be treated effectively by cone biopsy; 4) endocervical glandular dysplasia is not a reproducibly recognizable lesion, and its behavior and existence are undefined; 5) criteria exist to permit the distinction of early invasive adenocarcinoma from AIS in about 80% of cases; 6) microinvasive adenocarcinoma of the cervix is complicated by the presence of multiple definitions; clinical decision making is best guided by assessment and reporting of the depth, horizontal extent, and presence of lymphatic or vascular invasion.     

Human papillomavirus associated with adenocarcinoma and adenosquamous carcinoma of the cervix: analysis by in situ hybridization

The incidence of adenocarcinoma of the cervix appears to be increasing. Recent reports have demonstrated an association between adenocarcinoma of the cervix and human papillomavirus (HPV) by Southern blot hybridizations. In situ deoxyribonucleic acid (DNA) hybridization was performed on paraffin-embedded specimens to localize the source of HPV DNA. In pure adenocarcinoma five of six specimens were positive for HPV DNA. Four specimens contained HPV type 18 and one HPV type 16. Only one of three adenosquamous lesions was positive and it contained both HPV types 16 and 31. These findings suggest an association between HPV and adenocarcinoma of the cervix.     

Detection of human papillomavirus DNA in human cervical lesions by tissue in situ nucleic acid hybridization

Cervical cancer is one of the most common female cancers in Taiwan. Certain types of human papillomavirus (HPV) are frequently detected in the epithelial precancerous and cancerous lesions of the cervix. By the use of tissue in situ hybridization, we investigated the relationship of various types of HPV (group I, HPV-6 & 11, group II, HPV-16 & 18, group III, HPV-31, 33 & 35) with cervical condyloma, carcinoma as well as precancerous lesions. Group I HPV DNAs were mainly found in cervical condylomatous lesions (2/2) of the cervix and cervical intraepithelial neoplasia I (CIN I) (2/4), but were only occasionally found in CIN II (1/4), CIN III (1/9) or non-keratinized squamous cell carcinoma (1/15). HPV DNAs of groups II and III were mainly detected in lesions of CIN III (5/9) and invasive squamous cell carcinoma (large cell, keratinized type: 4/7; large cell, non-keratinized type: 11/15). HPV DNA sequences were invariably detectable only in the cell nuclei of condyloma or dysplastic epithelium or invasive carcinoma. However, they could not only be detected in the upper layer dysplastic cells and koilocytes but also in the well and poorly differentiated cervical cancer cells. The distribution of HPV DNA positive cells in the carcinomas fell into four different patterns: (1) upper zone and non-invasive regions of the carcinoma (11/22, 50%), (2) basal zone and invasive regions (2/22, 9%), (3) randomly scattered (7/22, 32%), and (4) extensively distributed over the whole tumor lesions (2/22, 9%). Thus, our results are consistent with a strong correlation between the presence of HPV-16, 18, 31, 33 and 35 and malignant conversion of cervical epithelial cells.     

In situ adenocarcinoma of the uterus cervix: difficulties of its cytohistological diagnosis

In situ adenocarcinoma is regarded as the precursor of invasive adenocarcinoma. It is asymptomatic and early diagnosis relies solely on cytopathologist. It is usually discovered on a cone for squamous CIN. When diagnosis is made by biopsy, conisation is required to exclude invasive adenocarcinoma. Lesion is histologically characterised by epitheliomatous transformation of endocervical glands without invasion of the chorion. By the appearance of glandular cells, different histological varieties are described. They have no influence on the prognosis. Several benign lesions may mimic adenocarcinoma: tubal metaplasia, glandular atypia due to inflammation or irradiation, mesonephric remnants and microglandular hyperplasia. Precursor lesions (atypical hyperplasia, glandular dysplasia, CIGNI and II) are badly morphologically defined. Preferential location of in situ adenocarcinoma is the transformation zone. Because of this topography, if the surgical margins are disease free, conisation alone may be adequate therapy. HPV infection (mainly HPV 18) are incriminated in its pathogenesis.     

Variants of human papillomavirus types 16 and 18: histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in cervical smear.

Human papillomavirus (HPV) genotypes cannot fully explain the histological diagnosis of women with glandular abnormalities detected by cervical smear. Thus, this study was designed to analyze the distribution of HPV-16 and HPV-18 variants in women referred because of atypical glandular cells and adenocarcinoma in situ in their cervical smears and its association with histological results. Twenty-four women with HPV-16 and 6 with HPV-18, selected from 160 women with cervical smears suggestive of glandular abnormalities, were included. Histological results showed cervicitis (1 case), squamous neoplasia (18 cases), glandular neoplasia (7 cases), and glandular neoplasia associated with a squamous component (4 cases). Among the 24 cases presenting HPV-16, the European variant was detected in 15 (62%) and the Asian American in 9 (38%). Among the 15 cases associated with the European variant, 14 (93%) presented squamous neoplasia and 1 (7%) invasive adenocarcinoma. Asian-American HPV-16 variants were significantly associated with histological diagnosis of glandular neoplasia alone (odds ratio, 9.3 [1.4-60.2]) or associated with squamous neoplasia (odds ratio, 18.7 [1.5-232.3]). Adenocarcinomas were detected in 4 of 6 HPV-18-positive cases, being 2 cases had the European variant, 1 had the Asian Amerindian variant, and 1 had the African variant. The association of HPV-16 with squamous or glandular neoplasia is explained by its variants. In this study, squamous neoplasia was related to the European variant of HPV-16, whereas glandular neoplasia was related to the Asian-American variant. Glandular neoplasia is associated with HPV-18, but the results of our analysis of its variants were inconclusive.     

Cervical glandular intraepithelial neoplasia topography and the risk of conisation

OBJECTIVES: The frequency of endocervical adenocarcinoma is increasing in comparison with squamous cell carcinoma and it presents a very difficult diagnostic and therapeutic problem. DESIGN: The aim of this study was: 1) Evaluation of topography of the cervical glandular intraepithelial neoplasia (CGIN) 2) An analysis of the Human Papillomavirus (HPV) infection rate in samples. MATERIALS AND METHODS: 360 amputated uterine cervix samples with histologically-proven diagnosis of cervical intraepithelial neoplasia (CIN-3) were evaluated. The coexistence of pre-invasive lesions in squamous epithelium and endocervical columnar cell were investigated. Moreover CGIN topography and retrospective histopathological analysis were determined. A polymerase chain reaction (PCR) was performed using commercially available PCR Human Papillomavirus Typing Set to detect HPV infection. RESULTS: Among 360 positive cervical intraepithelial glandular neoplasia samples (CIN-3) 71 (19.7%) showed coexisting glandular lesions (CGIN-1, 2, 3). The lesions in endocervical glandular cells of CIGN-type were distributed from the distance up to 14 mm from the surface of cervix. Most of them were located no deeper than 1 mm from the surface of canal epithelium. HPV DNA was found in more than 90 preneoplastic glandular proliferations. The frequency of oncogenic HPV-16 and 18 presence was higher than non-oncogenic HPV. CONCLUSIONS: 1. CIN-3 is associated in about 20% with cervical glandular intraepithelial neoplasia (CGIN). 2. Topography of CGIN is important in planning the management. 3. Most of CIGN are associated with HPV infection.     

Absence of human papillomavirus infection in minimal deviation adenocarcinoma and lobular endocervical glandular hyperplasia.

The human papillomavirus (HPV) is basically always detected in squamous cell carcinoma of the cervix and its precursors; a high incidence of HPV also has been reported in adenocarcinoma and adenocarcinoma in situ of the uterine cervix. Lobular endocervical glandular hyperplasia (LEGH) was first described by Nucci in 1999. It is difficult to differentiate minimal deviation adenocarcinoma (MDA) from LEGH preoperatively or postoperatively by clinical and pathologic features. The relationships between HPV and MDA or LEGH have not been studied well because of the rare incidence of the two diseases. To our knowledge, the HPV status in LEGH has not been reported. This study was designed to investigate HPV infection in MDA and LEGH, using the polymerase chain reaction (PCR) technique. Tumor tissue lesions were microdissected and the detection of HPV and its typing were analyzed by PCR-based assay. As the control, HPV DNA was detected in all cases of squamous cell carcinoma and three of five cases of adenocarcinoma. However, no HPV DNA was detected in any of the 10 cases of LEGH or in the 3 cases of MDA. These results suggest that MDA and LEGH are probably not related to HPV infection.     

Human papillomavirus detection in cervical lesions nondiagnostic for cervical intraepithelial neoplasia: correlation with Papanicolaou smear, colposcopy, and occurrence of cervical intraepithelial neoplasia

Human papillomavirus (HPV) is associated with cervical intraepithelial neoplasia (CIN) and carcinomas. The present study involved women who had an abnormal Papanicolaou smear and whose cervix contained acetowhite area(s) that lacked the histologic features of CIN. Sequences homologous to HPV DNA, determined by Southern blot hybridization analysis, were detected in 20 of 59 cervical biopsy specimens (34%) that lacked the histologic features of CIN. When compared with the group in which HPV DNA was not detected, the HPV DNA-positive group had a lower chance of having a normal Papanicolaou smear (30 versus 61%) at the time of the biopsy. There was no difference in the colposcopic findings between the HPV DNA-positive and -negative cases for the biopsy specimens that lacked the features of CIN. However, there was a difference in the rate of histologically proved CIN in the two groups. Twelve of 17 women (71%) in the HPV DNA-positive group for whom there was follow-up information had a biopsy-proved CIN lesion noted at another location in the cervix at the time of biopsy (six) or 3-12 months after the biopsy (six). This rate was significantly higher (P less than .05) than the rate (five of 25, 20%) in the HPV DNA-negative cases, most of whom had no colposcopic abnormalities and a normal Papanicolaou smear at the follow-up examination. These findings indicate that HPV DNA detection in women with cervical lesions that lack the histologic features of CIN predicts current or future CIN in such patients.     

In situ hybridization analysis of human papillomavirus DNA segregation patterns in lesions of the female genital tract

Various histologic features may be used to divide human papillomavirus (HPV)-related lesions of the genital tract into two groups: condylomata and "low-grade" or grade 1 cervical intraepithelial neoplasias (CIN 1) versus "high-grade" or grade 2 and 3 intraepithelial neoplasias. Using in situ hybridization analysis we correlated HPV DNA type with histologic features in 350 biopsies of lesions from the cervix, vulva, and perianal region. HPV DNA was most commonly found in vulvar and perianal condylomata (39/46, 85%), whereas the rate in CIN 1 lesions was 72% (86/120). The rates were 53% (40/76) and 57% (12/21) in CIN 2/3 and vulvar intraepithelial neoplasm (VIN) grades 2 and 3, respectively. The HPV type in all but 2 of the 39 perianal and vulvar condylomata which contained HPV was 6/11. Despite their similar histologic features, the HPV type in only 23 of 86 (27%) CIN 1 cases with detectable HPV was 6/11 compared to 31 of 86 (36%) which contained HPV 16-related DNA and 32 of 86 (37%) which contained HPV 31,-33, or -35-related DNA. The viral DNA in the majority of CIN 2/3 lesions and all of the VIN 2/3 lesions was HPV-16 related; no CIN 2/3 or VIN 2/3 lesion had HPV 6/11-related DNA. It is concluded that although cutaneous genital tract condylomata are highly associated with HPVs of low oncogenic potential (types 6 and 11), these HPV types are not as frequent as the oncogenic HPVs (16, 31, 33, and 35) in CIN 1 lesions. Further, HPV 6/11 appears to be very rarely associated with CIN 2/3 or VIN 2/3 lesions.     

Human papillomavirus associated with adenocarcinoma and adenosquamous carcinoma of the cervix: Analysis by in situ hybridization

The incidence of adenocarcinoma of the cervix appears to be increasing. Recent reports have demonstrated an association between adenocarcinoma of the cervix and human papillomavirus (HPV) by Southern blot hybridizations. In situ deoxyribonucleic acid (DNA) hybridization was performed on paraffin-embedded specimens to localize the source of HPV DNA. In pure adenocarcinoma five of six specimens were positive for HPV DNA. Four specimens contained HPV type 18 and one HPV type 16. Only one of three adenosquamous lesions was positive and it contained both HPV types 16 and 31. These findings suggest an association between HPV and adenocarcinoma of the cervix.     

Human papillomavirus DNA detection and histological findings in women referred for atypical glandular cells or adenocarcinoma in situ in their Pap smears

OBJECTIVE: To evaluate the association between high-risk human papillomavirus (HPV) DNA detection and histological diagnosis in women referred for atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) at Pap smear. METHODS: In this cross-sectional study, 146 women referred for AGC (124), AGC with high-grade squamous intraepithelial lesion (HSIL) (15), or AIS (7) were tested for HPV DNA using Hybrid Capture II (HC II). All women underwent colposcopic examination, and cervical biopsy was performed for 95 patients. Fifty-one women referred due to AGC with normal colposcopy and normal second Pap smear were scheduled for control visits every 4 months. RESULTS: The overall prevalence of HPV DNA was 38%. HPV DNA was detected in 93% of the women with HSIL associated with AGC and in 71% of women with AIS Pap smear, being significantly higher when compared with the prevalence (29%) in women with AGC alone. Forty-five women (30.8%) had clinically significant histological lesions (CIN 2 or worse). High-risk HPV DNA was detected in only 16% of the women without significant abnormalities in biopsy, in contrast to 96% of those who had CIN 2 or CIN 3 and 75% of women with AIS. Eighty-five percent of women with invasive cervical carcinoma (squamous or adenocarcinoma) tested positive for HPV DNA. HPV DNA detection was significantly associated with histological diagnosis of CIN 2 or worse, with an odds ratio (OR) = 51.8 (95% CI 14.3-199.9). CONCLUSION: HPV DNA detection was strongly associated with the severity of cervical lesion (CIN 2 or worse) in women referred for AGC or AIS in their Pap smear. These data implicate the use of HPV testing in triage of women with AGC Pap smears.     

Human papillomavirus type 16 in multifocal neoplasia of the female genital tract

We examined lesions from six women with multifocal neoplasia of the lower genital tract (vulva and cervix or vulva and vagina) for the presence of human papillomavirus (HPV) DNA sequences by DNA-DNA in situ hybridization. Cervical tissue specimens from four of the five women with carcinoma in situ (CIS) of the cervix were found to contain HPV type 16 DNA sequences. Vulvar lesions from three of these women also contained HPV-16 DNA and were histologically consistent with CIS. In each instance, hybridization with HPV-16 DNA probes was seen only in areas of the epithelium that contained evidence of surface maturation or koilocytotic atypia (KA). The HPV DNA was not visualized in regions of these lesions in which the full thickness of the epithelium was occupied by poorly differentiated cells. Virus capsid antigens were only detected in a very few cells in two of the four cervical lesions that contained HPV-16 DNA. HPV type 16, which has consistently been associated with the development of cervical cancer, is further implicated as an agent in the pathogenesis of genital cancers by demonstration of the virus genome in neoplasia at nonadjacent sites.     

Cytologic and biopsy findings leading to conization in adenocarcinoma in situ of the cervix

OBJECTIVE: To investigate the utility of currently available screening tests in preoperatively detecting adenocarcinoma in situ of the cervix. METHODS: Patients with a cone biopsy diagnosis of adenocarcinoma in situ from 1987 to 2000 at our institution were identified. Results from Papanicolaou smears, cervical biopsies, and endocervical curettages preceding the diagnostic cone biopsy were collected from medical records and referring providers. Fisher exact test (two-tail) was used for statistical analysis. RESULTS: The preoperative screening results preceding a cone biopsy containing adenocarcinoma in situ were available in 118 patients. Among 94 Papanicolaou smears, 65 (69%) glandular lesions and 29 (31%) squamous or unspecified lesions were reported. Biopsy and/or endocervical curettage after the 29 squamous or unspecified lesions on Papanicolaou smear detected 15 additional glandular lesions, totaling 80 (85%) of 94 cases of glandular disease detected before conization. Among all 118 cases with some form of preoperative data available, glandular disease was predicted in 100 cases (85%). In cases of suspected glandular disease, 86% were treated with cold knife cone compared with 22% in cases of suspected squamous abnormalities (P <.001). CONCLUSION: The sensitivity of detecting a glandular abnormality before a cone biopsy containing adenocarcinoma in situ is 69% with the Papanicolaou smear and 85% with the addition of biopsy and endocervical curettage. This underscores the importance of using preoperative assessment to appropriately plan treatment for a suspected glandular lesion.     

Detection of HPV DNA in the uterine cervical lesions by polymerase chain reaction and in situ hybridization]

Human papillomavirus (HPV) is found in close association with carcinogenesis of the uterine cervix. We applied a new in vitro gene amplification technology, the polymerase chain reaction (PCR) to detect HPV 16 and 18 in cervical exfoliated cells. HPV infections were detected in 5 (16%) of 31 women with no pathological lesions of the uterine cervix (normal), 16 (24%) of 67 with cervical intraepithelial neoplasia (CIN) and 6 (38%) of 16 with invasive cervical cancer. Moreover, 10% formalin-fixed and paraffin-embedded tissue sections were prepared from the uterine cervix of these 27 women with PCR-proven HPV infection and were examined for the histological localization of HPV-DNA by in situ hybridization with biotin-labeled DNA probes of HPV types 6/11, 16/18 and 31/33/35. HPV-DNA type 16/18 was detected in 3 of 5 normal women, 2 of 4 CINs I, 2 of 3 CINs II, 6 of 9 CINs III and 6 of 6 invasive cervical cancers. HPV-DNA type 6/11 was detected in 6 of 6 condylomas. Viral DNA sequence was detected in the superficial cells of CIN I and II, and it was distributed through entire thickness layer of undifferentiated cells derived from CIN III and squamous cell carcinoma. In addition, the staining intensity became weak as the lesion progressed. These differences between lesions might be due to the difference in the viral form in the nuclei, ie whether an episomal or integrated form. Thus, an in situ hybridization technique with a biotin-labeled DNA probe as well as the PCR method is useful for the detection of HPV in clinical samples.     

Prediction of high-grade cervical disease with human papillomavirus detection in women with glandular and squamous cytologic abnormalities

The objective of this study was to assess whether human papillomavirus (HPV) detection with hybrid capture II (HC II) can help predict the presence and the nature, glandular or squamous, of histologic cervical lesions in women referred due to atypical glandular cells (AGC) or high-grade squamous intraepithelial lesion (HSIL). A total of 247 women were included. Referral Pap smears comprised AGC (51 cases), AGC plus HSIL (28 cases), adenocarcinoma in situ (10 cases), and HSIL (158 cases). All patients were tested for high-risk HPV with HC II and had a histologic assessment of their cervix. Histologic analysis showed 38 women with (15.3%) cervicitis, 194 with (75.5%) squamous lesions, and 15 with (9.2%) glandular neoplasia. The overall rate of high-risk HPV detection was 77%. Almost 70% of AGC-HPV-negative patients did not have a pathologically proven cervical neoplasia, whereas 76% of women with AGC-HPV-positive result were diagnosed with a squamous or glandular neoplasia. Most (95%) of the lesions in patients with AGC-HSIL were of squamous nature, and HPV detection did not contribute to their differentiation from glandular lesions. We conclude that in women with AGC, HPV positivity strongly correlated with the presence of glandular or squamous cervical lesion but did not help distinguishing women with squamous from those with glandular neoplasia.     

Detection of human papillomavirus DNA in cervical lesions by in situ hybridization using biotinylated DNA probes

In situ hybridization (ISH) for human papillomavirus (HPV)-6, -11, -16, -18, and -31 DNA was performed on 615 formalin-fixed paraffin-embedded cervical biopsies using biotinylated DNA probes. Results were obtained from 584 samples with 266 (45.5%) containing HPV-DNA sequences. Ninety percent of condyloma acuminatum specimens were positive for HPV-DNA with 18 of 19 positive cases containing HPV-6 or -11 DNA. The detection rate of HPV in cervical intraepithelial neoplasia (CIN) lesions was 50.6% (239 of 472), while only 8 of 91 (8.9%) cervical biopsies considered to be histologically normal or with minimal dysplasia contained HPV-DNA as demonstrated by ISH. The prevalence of HPV-16, -18, and/or -31 DNA increased with the severity of the lesions, with 20 of 20 (100%) positive CIN-III lesions containing these viral types compared with 102 of 157 (65.0%) positive CIN-I lesions. ISH with biotinylated DNA probes appears helpful in identifying lesions containing higher risk viral strains.