Genital human papilloma virus infection in Oslo studied by dot blot DNA hybridization and the polymerase chain reaction.

Samples from patients with genital condyloma acuminata or with cervical condylomas and/or dysplasia and from women without cytological/clinical evidence of cervical affection were examined by dot blot DNA hybridization or the polymerase chain reaction (PCR). The PCR was much more sensitive than dot blot, more than doubling the human papilloma virus (HPV) findings. HPV DNA, mainly HPV 6/11, was detected in 18 of 19 biopsies of condyloma acuminata, whereas HPV 16 was most frequently detected in the 21 cervices (76%) with condyloma and/or dysplasia. HPV 16 was detected in eight of 103 cervical smears with no signs of infection. The prevalence of HPV 16 in cervical samples was somewhat higher than expected. This suggests that, in Oslo, HPV 16 is a common HPV type in women with cytologically normal cervices. HPV 18 was relatively rare and was detected only in combination with other HPVs.     

Human papillomavirus coinfections of the vulva and uterine cervix

DNA filter in situ hybridisation (FISH) was used to determine the presence of human papillomavirus (HPV) genotypes 6/11, 16/18, and 31/33 in cell scrapes of the cervix and vulva of 128 women who had precancerous lesions and/or HPV infection of the cervix diagnosed by cytology, colposcopy, and histology. HPV-DNA was found in 87 (68%) vulval and 95 (74%) cervical cell scrapes, and in both the vulval and cervical scrapes of 73 (57%) women, but not in either the vulva or the cervix of 19 women (15%). Of the HPV-DNA-positive smears, the prevalence of the HPV types was 61% HPV 16/18, 14% HPV 6/11, 3% HPV 31/33, and 22% HPV 6/11 and 16/18. By contrast, HPV-DNA was not detected in the cervical smears of a control group of 35 women who were assessed to be free of cervical abnormalities by colposcopy and cytology. The epithelial response of the vulva and the cervix to application of 5% acetic acid was assessed by colposcopy and the results correlated with the presence of HPV genotypes. A possible or definite disorder of the cervix and vulva was detected by colposcopy in 95 (74%) and 96 (75%) of the 128 cases, respectively. The colposcopic assessment of the vulva was inconclusive in ten cases (8%), and only eight women (6%) were found to be free of both a vulval and cervical disorder. This study shows subclinical papillomavirus infections of the vulva frequently coexist with HPV infections and precancerous lesions of the cervix.(ABSTRACT TRUNCATED AT 250 WORDS)     

DNA image cytometry and human papillomavirus (HPV) detection help to select smears at high risk of high-grade cervical lesions

Three samples were submitted from women undergoing routine screening (n=910): two smears (one for routine cytology and one for DNA image cytometry) and a scrape for human papillomavirus (HPV) testing. DNA histograms were classified as suspect in cases of aneuploidy, polyploidy, and/or diploidy with a high proliferation rate. Follow-up was available in 239 cases. The primary end-point was the presence of a high-grade squamous intraepithelial lesion (HGSIL) at biopsy. Seventy women (7.7%) had a high-risk (HR) HPV infection and a suspect DNA profile. In 77 women with cytological abnormalities, 28 HGSILs were detected: four with a prior diagnosis of ASCUS (all HR-HPV infected including three with a suspect DNA profile), three with smears evocative of LGSIL (all with HR-HPV infection and a suspect DNA profile), and 21 with smears evocative of HGSIL (all with HR-HPV infection and 20 with a suspect DNA profile). During the follow-up period, out of 239 women with a cytologically normal smear at first entry, five developed a HGSIL; all were HR-HPV-positive and four had a suspect DNA profile at the first smear. HR-HPV detection alone gives a sensitivity of 100% for the detection of HGSIL, with a specificity of 84.3%, whereas DNA measurement associated with HPV testing significantly enhances the specificity to 95.4%. Thus, the combination of HPV testing and DNA measurement provides a highly sensitive and specific evaluation of the risk of HGSIL on cervical smears.     

Time trends in the prevalence of human papillomavirus infections in archival Papanicolaou smears: Analysis by cytology,DNA hybridization,and polymerase chain reaction

A retrospective study was undertaken to determine the prevalence of human papillomavirus (HPV) infections in routine Papanicolaou (Pap) smears collected by general practitioners from Western Australian women in each of the years 1972, 1982, and 1987. HPV infection was detected by cytology, dot-blot hybridization, or polymerase chain reaction (PCR). It was found that the prevalence of HPV infection remained unchanged over the 15 year study period, was independent of age, and was associated with normal cytology at a rate far greater than previously recognized. Indeed, the prevalence of cervical intraepithelial neoplasia (CIN) lesions, as detected by cytology, was 3.0% in 1972 and 3.8% in 1982 and 1987. The prevalence of HPV infection, detected as koilocytosis or parakeratosis, was 6.5%, 6.8%, and 5.3% in smears collected in 1972, 1982, and 1987, respectively, from 1,800 women. In 237 cytologically normal smears reprocessed for HPV-DNA studies, the prevalence of HPV 16 was determined to be 15.6%, 11.2%, and 17.8% in 1972, 1982, and 1987, respectively, as determined by dot-blot hybridization. However, the PCR detected HPV 16 in an additional 55.5%, 62.9%, and 57.0% of cytologically normal and dot-blot negative smears. The prevalence of HPV 16 infection in cytologically normal smears was estimated to be 71.0%, 74.1%, and 74.8% in 1972, 1982, and 1987, respectively, by combining the HPV 16 dot-blot and PCR-positive results. The high prevalence of HPV 16 in cytologically normal Pap smears suggests that infection with HPV 16, as detected by PCR amplification, does not place women in a high-risk category for cervical cancer. In addition, we have shown that the application of PCR on reprocessed Pap smears is a powerful and sensitive method for retrospectively evaluating any aetiological role of HPV infection in the development of cervical cancer.     

Oral contraceptive use and human papillomavirus infection in women without abnormal cytological results

Both experimental and epidemiological data support the idea that oral contraceptive (OC) use may have a stimulating effect to a certain point on cervical carcinogenesis. The current investigation tries to answer the question whether OC use might have an influence on early human papillomavirus (HPV) infections. A total of 425 women without abnormal cytological results were examined colposcopically, and filter in situ hybridisation (FISH) was used to determine the presence of human papillomavirus (HPV) types 6, 11, 16 and 18. Eighty-one cervical specimens (19.1%) were found to be positive for one or more of the HPV types in FISH. HPV positivity was found to correlate with age and parity, being the highest among women under 25 and with less than two births. The use of OCs was inversely correlated with the presence of ectopy or dysplasia in this group of women. On the other hand, HPV positivity was not significantly higher among OC users than among non-users in any colposcopic group. Neither the type of pill used, nor the duration of use had any significant effect on HPV positivity. Further investigations are needed to evaluate the effects of OC use on more severe HPV- induced cervical lesions.     

Prevalence of human papillomavirus infections among heterosexual men and women with multiple sexual partners.

A prospective study of 65 men and 111 women with multiple heterosexual partners was designed to assess the prevalence and potential risk factors of genital human papillomavirus (HPV) infections. In addition, the HPV reservoir in genital, rectal, and oral mucosa was examined. The specimens for the detection of HPV DNA were taken from different sites such as the urethra and coronal sulcus (men), cervix and labia minora (women), anus, rectum, tongue, and buccal mucosa (both men and women). Women underwent speculum examination and colposcopic evaluation of the anogenital region, and a smear for routine cytological classification was also taken. In men, the anogenital region was examined clinically and colposcopically. The polymerase chain reaction (PCR) was used for the detection of HPV types 6/11, 16, 18, and 33. A high prevalence of HPV infection at one or more sites was detected, in 32% of the male and in 23% of the female participants. Seventeen percent of the male distal urethral specimens were positive for HPV DNA. From the female cervical specimens 14% were found positive. Ten proctal specimens (five men and five women) were positive for HPV DNA without any discernible lesion. The persons from whom these samples were taken denied anal insertive intercourse. No oral manifestation of HPV infection was detected. In both men and women a difference between HPV DNA-positive and -negative persons was not found in relation to known risk factors associated HPV infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vaginal dysplastic lesions in women with hysterectomy and receiving radiotherapy are linked to high-risk human papillomavirus

Patients undergoing radiotherapy for advanced cervical and endometrial cancer bear a considerable risk of developing vaginal preneoplastic lesions. Radiotherapy itself has been considered to have a role in the pathogenesis of vaginal dysplasia, although human papillomavirus (HPV) involvement has also been suggested. A series of 88 patients who underwent hysterectomy and were irradiated for gynecological cancer, including 43 with postradiation vaginal dysplasia at colposcopy and 45 without vaginal lesions, were included in this study. Detection and genotyping of HPV DNA in vaginal scraping were carried out by a PCR-based method and compared with colposcopic and cytological findings and with other clinical and laboratory data. Forty-two (97.7%) colposcopy-positive subjects and 6 (13.3%) colposcopically-negative patients were PCR-positive for high-risk HPV DNA (P < 0.000001). Twenty-two out of the 43 patients with colposcopic lesions showed an abnormal Papanicolau (PAP) test. Cytologic examination was negative in all colposcopically negative women. Type 16 HPV DNA was more frequent in patients with high-grade squamous intraepithelial lesions and in patients treated with external radiotherapy, whereas other types of high-risk HPV were more common in patients with low-grade lesions and in those treated with brachytherapy. When considering colposcopy as the standard for diagnosing vaginal dysplasia, HPV DNA testing was more sensitive than the PAP test. However, the specificity of the PAP test was higher with no false-positive case. In conclusion, vaginal preneoplastic changes in women post-hysterectomy and receiving radiotherapy for cervical, endometrial, and vaginal cancer represent an HPV-related nosologic entity. Whereas colposcopic examination can detect these preneoplastic lesions, HPV genotyping is a sensitive, inexpensive, and noninvasive method that may complement colposcopy and the PAP test.     

Use of the same archival papanicolanou smears for detection of human papillomavirus by cytology and polymerase chain reaction.

An optimal method for the processing of archival cervical Papanicolaou (pap)-stained smears for the amplification of human papillomavirus (HPV) DNA by polymerase chain reaction (PCR) was developed. This methodology was then applied to a series of 44 pap smears designated as HPV positive or negative (on the basis of both major and minor cytological criteria) or cervical intraepithelial neoplasia (CIN)-cancer. For the detection of HPV DNA, each sample was tested with the consensus GP5/6 primers, and when negative, with CPI-IIG primers. The HPV DNA was detected in 100% (8 of 8) of CIN-cancer smears using the GP5/6 primers. In smears with cytological evidence of HPV without CIN. the use of both sets of primers yielded positive results in 100% (19 of 19) of the samples. Direct sequence analysis of PCR products showed that 16 of the 27 HPV-positive samples contained more recently described HPV types. When tested with both primer combinations, all 17 cytologically negative smears were positive for beta-globin but negative for HPV DNA. The findings show the value of using archival pap smears for further investigations to address issues such as latency, but they indicate that cytological criteria and DNA technology will be critical factors in the reliability of the results.     

Filter in situ hybridisation: an evaluation of the FISH technique for HPV detection in cervical swabs

The filter in situ hybridisation (FISH) method for detection of HPV in cervical swabs was evaluated against the Southern blot technique on concomitant cervical biopsies. Of 73 biopsies, HPV 16 DNA sequences were found in 26 biopsies and HPV 18 sequences in 2 biopsies. Analysis by FISH of the corresponding smears detected 58 and 100% of these, respectively. Of the smears corresponding to the HPV-negative biopsies, 17% were HPV 16-positive and 3% were HPV-18 positive by FISH. Re-hybridisation with cold plasmid added for competition did not change these results. To estimate the risk of spurious hybridisation between vector remnants in the probe and bacterial DNA sequences present in smears, we have hybridised by FISH to preparations of the 19 most common vaginal microorganisms. Of these, E. coli, which is present in about 10% of cervical smears, hybridised strongly with a probe of the plasmid vector pBR322 and may be a significant cause of false positive FISH results. None of the bacteria hybridised with probes of purified HPV when cold, denatured plasmid was added for competition. Analysis by FISH with probes of purified pBR322 to 167 smears of a patient control group resulted in 6% positive reactions. In hybridisations with probes of HPV 16 and 18 to 2 or 3 different filter preparations of the same smear, identical results were obtained in 18 of 19 smears, indicating a good reproducibility by the FISH method. The high percentage of HPV negative smears is equivalent to the rates known from cytology and may reflect sampling errors.     

Infections of the cervix uteri with human papillomavirus and Chlamydia trachomatis.

Apart from infection with human papillomavirus (HPV), other microorganisms may be involved in the development of cervical neoplasia. To study concomitant infections with HPV and Chlamydia trachomatis, cervical specimens from 4 groups of women were examined for the presence of these microorganisms by the polymerase chain reaction. The first group consisted of 143 consecutive samples from women with no cytological abnormalities who participated in a triennial screening program to prevent cervical cancer. In this group 2 samples were found positive for HPV and 2 additional samples were found positive for C. trachomatis. In the second group of 46 cytologically abnormal smears, HPV DNA was detected in 71.7% of the samples and C. tra chomatis in 4.3%. In a third group of 94 histological abnormal biopsies, the HPV prevalence ranged from 15% in mild dysplastic lesions up to 92% in invasive cervical carcinomas. Only 2 biopsies of this group (2.1%) were found positive for C. trachomatis. Finally, a group of cervical scrapes was obtained from women attending a clinic for sexually transmitted diseases. In 52 samples positive for C. trachomatis and 60 samples negative for C. trachomatis, no significant (P = 0.57) difference in the frequency of HPV infections was found (11.5% and 8.3%, respectively). The data show that in these study groups HPV and C. trachomatis are independently occurring agents.     

Biological behavior and etiology of inflammatory cervical smears

Two hundred and fifty-seven consecutive women attending a major maternal and child health (MCH) center were studied clinically, colposcopically, cytologically, and microbiologically for different gynecologic infections. Out of 257 cases, 207 (80.5%) had inflammatory cervical smears, of which 183 (88.4%) were infected with one or more genital tract infections. Bacterial vaginosis (risk, 22.6-fold), chlamydia (risk, 21.6-fold), and human papillomavirus (HPV) (risk, 13.5-fold) were independently associated with inflammatory smears. In addition, significantly higher proportions of women with inflammatory smears had cervical ectopies (28.5% vs. 10.2%) and bleeding ectopies (30.9% vs. 4.1%) as compared to noninflammatory smears. Women infected with bacterial/parasitic genital infections were given specific treatment. These women were followed up at regular intervals to assess the efficacy of antimicrobial therapy. During follow-up examination, only 26 women (12.6%) showed negative smears. Sixteen women developed squamous intraepithelial lesions (SIL) during follow-up, and 163 women had persistent inflammatory smears. Multivariate analysis revealed that persistent inflammatory smears were associated with herpes simplex virus (HSV) infection, as revealed through detection of IgA antibodies to HSV (risk, 11.5-fold). Progression of SIL was associated with HPV infection (risk, 17.6 fold). Thus, inflammatory smears are associated with different types of infection, most of which do not respond to antimicrobial therapy.     

Detection by PCR of human papillomavirus genotypes in cervical lesions of Senegalese women

In order to analyse human papillomavirus (HPV) infection in the Senegalese population, HPV DNA was sought in 65 women with evidence of cervical cytological abnormality and in 72 pregnant women. Ninety-four percent of the patients were positive for HPV DNA as compared to 24% of pregnant women. HPV 16 was detected in cervical smears in 42% of cases, HPV 18 in 39%, HPV 6 in 26%, HPV 11 in 15%, HPV 45 in 10%, HPV 52 in 3%, and HPV 31, HPV 33 and HPV 68 in 1.5%. HPV 16 and HPV 18 were detected in 16% and 7% respectively of pregnant women. HPV DNA of unknown type was detected in 6% of cases, and multiple HPV infections were observed in 28% of cases. Low risk genital HPVs (6/11) were detected in smaller proportions (17%) among high grade squamous intraepithelial lesions (SILs) than the low grade SILs (43%). High risk HPVs (16/18) were detected in high proportions both in low and high grade SIL lesions, though the highest frequency (70%) was observed among patients with high grade lesions. In conclusion, the results confirm that HPV infections are frequent in Senegal and that HPV 18 and 45 are detected in a high proportion of patients in Africa. © 1996 Wiley-Liss, Inc.     

Detection of transforming gene regions of human papillomavirus type 16 in cervical dysplasias by the polymerase chain reaction

In a study of 29 cases of histologically confirmed, characterized colposcopically and cytologically, cervical intraepithelial neoplasias 48.3% (14/ 29) of biopsies were positive for human papillomavirus (HPV) type 16 DNA by polymerase chain reaction. We used two oligonucleotide primer pairs (position 215–514 and 606–805) flanking a 300 and a 199 base pair fragment from the early 6 (E6) and early 7 (E7) genes. The results were concordant both with the E6 and with the E7 regions. Of the amplified products 85.7% (12/14) could be confirmed; these carried 16 specific sequences by Southern blot hybridization. HPV 16 DNA was present in 6.7% (2/30) of the colposcopically directed cytologically normal matched control samples using the same methods.     

Use of anticontamination primers in the polymerase chain reaction for the detection of human papilloma virus genotypes in cervical scrapes and biopsies

A reliable application of the polymerase chain reaction (PCR) for detection of the human papilloma virus (HPV) genotypes in cervical smears and biopsies was developed. Primers flanking the HPV cloning site were used to avoid detection of cloned HPV plasmids. These anticontamination primers were used for the specific detection of HPV 6, 11, 16, 18, and 33 in cervical scrapes that had been tested previously for HPV with a combined modified filter in situ hybridization (modified FISH) and dot blotting procedure. The PCR appeared to be superior. Two groups of women were screened for HPV genotypes. Group A consisted of women belonging to a regularly screened population, and group B contained women attending a gynaecological clinic. It appeared that the overall prevalence of HPV in cytologically normal scrapes in the first group was 6%, whereas in the second group 12% was found. In scrapes with cytological dysplasia, the prevalence of HPV in group A and B was approximately 40% and 60%, respectively. HPV 16 was present predominantly. In biopsies of squamous cell carcinomas of the cervix uteri, an HPV prevalence rate of 90% was found, all of which contained only HPV 16 and 18. These data indicate an important role for HPV detection in the screening of cervical scrapes to identify women with an increased risk of cervical cancer.     

Routine papillomavirus antigen staining of cervical punch biopsy specimens.

Immunocytochemical staining for papillomavirus antigen was carried out on 1147 consecutive cervical punch biopsy specimens over 12 months. Of 876 cases with cervical intraepithelial neoplasia (CIN) 351, were antigen positive and of 49 cases with histological evidence of human papillomavirus (HPV) infection but no CIN, 14 were positive. There were 204 cases reported to be normal on routine histological examination and 12 cases reported to show features suggestive but not diagnostic of HPV infection. Of the normal group, 24 (12%) were antigen positive and of the equivocal group, two were positive. In 122 of the normal or equivocal groups cytological examination was repeated at the time of colposcopy, and dyskaryosis was reported in 36. In only four cases was disease shown by HPV antigen staining when there was no diagnostic histological or cytological abnormality. HPV antigen staining assists in the recognition of the range of histological changes associated with productive HPV infection but is an insensitive test and has only limited value in supplementing histological and cytological examinations as a diagnostic aid in routine colposcopic pathology.     

Prevalence of human papillomavirus types 6, 11, 16, 18, 31, and 33 in a cohort of Greek women

To study HPV prevalence and HPV types 6, 11, 16, 18, 31, and 33 distribution in cervical smears in a cohort of Greek women. One thousand six hundred thirty-six samples were cytologically evaluated and molecularly analyzed, by PCR based assay. Abnormal cytology was identified in 997 women and 75.4% of them were HPV DNA positive, while 639 had normal cytology and 24.6% were HPV DNA positive. HPV was detected in 62.9% of 256 ASCUS smears, 89.3% of 516 LSIL, 86.7% of 60 HSIL and 47.3% of 165 with cervical carcinoma. Overall, HPV 11 was the most common type (13.4%), followed by 18 (10.3%), 6 (7.2%), 16 (6.4%), 31 (3.4%) and 33 (3.4%). Multiple infections with two (11.3%) or more types, primarily 11 and 18 (4.8%), were also identified. Low-risk types 11 and 6 were common in ASCUS (36.6% and 26.4%, respectively), and high-risk types 16 and 18 in HSIL (42.3% and 30.8%, respectively) and in cancer (51.3% and 41%, respectively). Multiple infections were detected in 2.2% of normal and 31.7% of HSIL. HPV prevalence was 75.4% in abnormal and 24.6% in normal cervical smears. HPV 16 and 18 were the most common types in cancer. Single infection with type 11 and multiple infections with 11 and 18 were more frequent.     

浙江沿海地区人群TTV和HPV混合感染研究

目的了解浙江沿海地区人群TTV与HPV混合感染状况,探讨TTV传播途径。方法建立巢式聚合酶链反应方法（nPCR）,对健康体检和患宫颈疾病妇女150例宫颈病变细胞学标本及其平行97例血清标本进行TTVDNA及TTV病毒滴度的nPCR检测;应用导流杂交方法检测95例宫颈病变细胞学标本的HPV基因型。结果TTVDNA在55例健康妇女宫颈细胞标本中检出率52．7％（29／55）,与其平行42例血清样本中检出率50．0％（21／42）。在患有疾病妇女宫颈细胞中TTVDNA检出率（74．7％）高于健康体检对照组（P=0．005）。TTVDNA在患者血清样本中检出率51％（28／55）。在宫颈细胞及其平行血清中均检测出TTV基因亚型G1b。TTV病毒滴度在宫颈细胞中高于在其平行血清10～1000倍。HPV在患者组中检出率98．9％（94／95）,在健康组中检出率27．3％（15／55）。HPV基因型是高危型HPV16、18、33和低危型HPV6。HPV阳性标本TTVDNA检测率明显高于HPV阴性标本（P=0．02）。结论TTV在宫颈细胞中具有高检出率,在宫颈细胞中TTV病毒滴度高于其平行血清。TTV与HPV随性传播感染人群,并在女性生殖道内繁殖。TTV与HPV协同作用有待研究。     

Colposcopy, punch biopsy, in situ DNA hybridization, and the polymerase chain reaction in searching for genital human papillomavirus (HPV) infections in women with normal PAP smears

To assess the prevalence of HPV infection in the genital tracts of women with normal PAP smears, a random series of 109 women was reexamined using colposcopy, a further PAP smear, and punch biopsies taken from the cervix (in 33 cases), vagina (212 cases), and anus (20 cases). The biopsy material was examined using routine histological investigations, in situ hybridization (ISH) with a 35S-labelled DNA probe cocktail (HPV 6, 11, 16, 18), and the polymerase chain reaction (PCR) to detect HPV DNA. Changes consistent with HPV infection were seen in 6.9% (18/262) of the biopsy specimens. Seven biopsy specimens (2.7%) from seven different women were found to contain HPV DNA using ISH. All of these ISH-positive lesions were diagnosed as morphologically characteristic HPV lesions: six flat condylomas and one papillary condyloma. Using PCR, the HPV DNA detection rate was highest in the cervical biopsy specimens (50%) and lowest (28.6%) in the anal biopsy specimens. A total of 35.5% of the 93 biopsy specimens studied using PCR contained HPV DNA. The commonest type was HPV 11 (54.5%), followed by HPV 18 (33.3%). Four of the nine biopsy specimens (44.4%) from colposcopically normal areas proved HPV DNA-positive using PCR. Of 17 biopsy specimens in which the histology was normal, seven were examined using PCR and three were DNA-positive. The discovery of HPV DNA using PCR in 32/92 of the biopsy specimens (34.8%) which had been found to be HPV DNA-negative when routine ISH was used is noteworthy. The results suggest that the light microscopy criteria currently used in diagnosing HPV infections are of no value in predicting latent HPV infections and that acetowhite staining is unable to distinguish between subclinical and latent infections on the one hand and changes unrelated to HPV on the other.     

Significance of a first-time atypical Papanicolaou smear in a young, high-risk African-American and Latino-American population.

The first atypical Papanicolaou smear in young, sexually active Latino and African-American women of low socioeconomic status may be predictive of underlying cervical neoplasia and human papillomavirus infection of significant quantity. The optimal management of first-time atypia on routine Pap smear has not been established. In many clinics, colposcopically directed sampling of the cervix is recommended only if atypia persists following specific or nonspecific treatment of cervicitis or after an arbitrarily determined time interval. Others recommend immediate colposcopic evaluation. To determine the best approach to the first-time atypical Pap smear in young minority women at high risk for the development of cervical cancer, 250 such patients were evaluated with colposcopically directed biopsy of the cervix prior to any form of therapy. Pap smears were repeated at the time of colposcopy. Histologically, there was evidence of cervical intraepithelial neoplasia in 41% of patients and human papillomavirus infection in 86%. Repeat Pap smears predicted the presence of cervical intraepithelial neoplasia in only 24% of patients. Immediate colposcopic evaluation represents the most prudent approach to the first-time atypical Pap smear in young, high-risk minority women.     

Human papillomavirus in false negative archival cervical smears: implications for screening for cervical cancer.

AIM--To assess the value of detecting human papillomavirus (HPV) DNA in false negative archival cervical smears in population based screening programmes for cervical cancer. METHODS--Cytomorphologically classified false negative archival Pap smears (n = 27) taken from 18 women up to six years before cervical cancer was diagnosed were blindly mixed with 89 smears from hospital patients with a variety of gynaecological complaints and tested for HPV by the polymerase chain reaction (PCR). Corresponding cervical cancer biopsy specimens were also available for HPV analysis. Neither the examining cytopathologist nor the molecular biologist was aware of the study design. RESULTS--HPV DNA was detected in the smears of 16 patients with cervical cancer missed previously by cytology. HPV 16 and 18 were found predominantly in those smears taken up to six years before the diagnosis of cervical cancer. The smears of the two remaining patients were reclassified as inadequate for cytology or contained no suitable DNA for PCR. In 15 patients the same HPV type could be found in the smears and the cervical cancer biopsy specimens. CONCLUSIONS--The results indicate that high risk HPV types can be detected in archival smears classified as false negative on cytology and that cytological screening errors may be reduced if combined with PCR testing for HPV.