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D R Scott

Publications and source records attributed to D R Scott.

At least 37 records · Page 2Linked to original sources
PubMed1998

A nested case-control study of dietary factors and the risk of incident cytological abnormalities of the cervix.

Several earlier case-control studies reported inverse associations of cervical squamous intraepithelial lesions (SIL) with high dietary or biomarker levels of carotenoids, folate, and vitamins C and E. However, most studies did not measure the primary causal factor, cancer-associated genital human papillomaviruses (HPV), now detected by sensitive viral DNA tests. This nested case-control study assessed whether high dietary intakes of these nutrients, plus zinc and vitamin A, reduced SIL risk in cancer-associated HPV DNA-positive women. Using a 60-item food-frequency questionnaire, nutrient estimates were obtained for 33 incident cases with high-grade lesions, 121 with low-grade lesions, 97 with equivocal SIL, and 806 cytologically normal controls sampled from a large prospective cohort study. Baseline cervicovaginal lavages were tested for HPV DNA by the polymerase chain reaction. Among DNA-positive cases (n = 68) and controls (n = 69), age-adjusted odds ratios (ORs) of SIL in the highest vs. the lowest nutrient quartiles were 1.4 [95% confidence interval (CI) = 0.5-4.2] for vitamin A, 0.6 (CI = 0.2-2.0) for beta-carotene, 1.3 (CI = 0.4-3.6) for vitamin C, 1.0 (CI = 0.4-3.6) for vitamin E, 0.7 (CI = 0.3-2.1) for folate, and 0.8 (CI = 0.3-2.2) for zinc. ORs in HPV DNA-negative women approximated 1.0, with the exception of vitamin E (OR = 0.5, CI = 0.3-0.9). These results do not support a protective role for the above nutrients against low-grade or equivocal SIL, which constituted the majority of diagnoses in this study.

Adult↗
PubMed1998

Human leukocyte antigen class I/II alleles and development of human papillomavirus-related cervical neoplasia: results from a case-control study conducted in the United States.

The host immune response to human papillomaviruses (HPVs) is believed to be an important determinant of progression of HPV-associated cervical neoplasia. Human leukocyte antigens (HLAs) are important in the presentation of foreign antigens to the immune system. Previous studies have suggested a possible association between HLA and cervical neoplasia, but the specific alleles found to be associated with disease have varied between studies. To further evaluate this issue, we conducted a nested case-control study within a 24,000-woman cohort study in the United States. A total of 711 women were selected for the study: 141 women diagnosed with high-grade squamous intraepithelial lesions (HSILs) of the cervix; 202 women diagnosed with low-grade SILs (LSILs); 166 women with no history of cervical neoplasia, but evidence of HPV-16 infection; and 202 women with no history of cervical abnormalities and who were HPV negative during follow-up as part of our cohort. Cervicovaginal lavage samples collected from participants were used for HPV testing by L1 consensus primer PCR and the Hybrid Capture tube test methods. DNA extracted from these same lavage samples were used for PCR-based HLA genotyping. Our results suggest a positive association between HLA B7 and HLA DQB1*0302 and disease. A negative association with disease was observed for HLA DRB1*1501-DQB1*0602 and DRB1*13. Associations were strongest when analyses were restricted to HPV-16-positive cases as follows. Compared with women who were cytologically normal and HPV negative, HLA B7 was associated with a 1.5-fold increased risk of HPV/LSIL [95% confidence interval (CI) = 0.95-2.5] and a 2.5-fold increased risk of HSIL (95% CI = 1.2-5.1). HLA DQB1*0302 was associated with a 1.5-fold increased risk of HPV/LSIL (95% CI = 0.94-2.4) and a 1.7-fold increased risk of HSIL (95% CI = 0.84-3.5). HLA DRB1*1501-DQB1*0602 was associated with a decreased risk of HSIL [relative risk (RR) = 0.21; 95% CI = 0.07-0.62]. HLA DRB1*13 was associated with a decreased risk of HPV/LSIL (RR = 0.78; 95% CI = 0.51-1.2) and HSIL (RR = 0.63; 95% CI = 0.30-1.3). Individuals who were either homozygous for DQB1*0302 or carriers of both B7 and DQB1*0302 were found to be at highest risk of disease (RR = 4.5, 95% CI = 1.5-14 for HPV/LSIL; and RR = 9.0, 95% CI = 2.4-34 for HSIL). No synergistic effect was observed for the alleles found to be associated with reduced risk of cervical neoplasia. Our findings support previous studies that have found HLA B7 and DQB1*0302 to be positively associated with cervical neoplasia and are consistent with those that have suggested that DRB1*13 is negatively associated with disease, but do not confirm previous assertions that DRB1*1501-DQB1*0602 increases the risk of cervical disease.

Adult↗
PubMed1997

Comparison of the hybrid capture tube test and PCR for detection of human papillomavirus DNA in cervical specimens.

The strong association of human papillomavirus (HPV) and cervical cancer makes it important to study HPV detection methods that may play a role in cervical cancer screening. We compared two DNA methods that are commonly used for HPV research in the United States: the MY09/MY11 L1 consensus primer PCR-based test and the first-generation Hybrid Capture tube method (HCT). Laboratory assays by each method were performed with 596 cervicovaginal specimens collected from participants in a large cohort study conducted in Portland, Oreg. Included were 499 specimens from women whose cytology was normal and 97 specimens from women with squamous intraepithelial lesions (SILs). The overall HPV DNA positivity for known types was 22.5% by PCR compared to 13.6% by HCT. When the analysis was restricted to the 14 HPV types detectable by both methods, the sensitivity of HCT, with PCR used as the standard for HPV status, was higher for specimens from women with concurrent SILs (81.0%) than for specimens from women with normal cytology (46.7%). Among specimens testing positive by both methods, 97.2% of the time the two methods agreed on whether specimens were positive for cancer-associated HPV types. Both of these HPV test methods provide information that supplements the information provided by the Pap smear. The PCR method has higher analytic sensitivity than HCT in detecting HPV, but HCT may be helpful in identifying women with concurrent SILs.

Cervix Uteri↗
PubMed1997

Evidence for at least two distinct groups of humoral immune reactions to papillomavirus antigens in women with squamous intraepithelial lesions.

Serological markers of squamous intraepithelial lesions (SILs), the precursors of cervical cancer, have not been studied extensively. To screen for antibody responses that might be associated with SILs, we measured IgG and/or IgA to nine antigens based on papillomaviruses, the infectious cause of SIL and cervical cancer, using an ELISA format. Cases were 59 women with low grade SIL (LSIL) and 38 with high grade SIL (HSIL). Controls were 50 women chosen to minimize the possibility that they ever had SILs [individuals who had no history of SIL and repeatedly tested negative for cervical human papillomavirus (HPV) DNA], frequency age-matched to cases. The data showed that five antibodies had strong positive associations with SILs and that one was inversely related to SILs. By studying these antibodies in pairs, furthermore, we found that case-control differences were enhanced. In particular, the combination of IgG to an epitope in the E6 protein of HPV 16 (E6:10) and IgA to HPV 16 virus-like particles (VLPs) was detected in 53% of LSILs and 65% of HSILs but only 9% of controls. These same responses were both negative in just 6% of LSILs and zero HSILs, compared to 59% of controls. Notably, E6:10 IgG and HPV 16 VLP IgA were not correlated with each other, and the other antibody responses positively associated with SILs could be broken into two groups: those correlated with E610 IgG and those correlated with HPV 16 VLP IgA. Overall, the data suggest that several papillomavirus antibodies may be strongly related to SILs, and that they can be divided into at least two independent groups of humoral immune reactions.

Antibodies, Viral↗
PubMed1997

Evaluation of PAPNET testing as an ancillary tool to clarify the status of the "atypical" cervical smear.

To assess the utility of the PAPNET system (Neuromedical Systems Inc., Suffern, NY) in clarifying the status of cervical smears showing borderline abnormalities, we analyzed the results of five cytotechnologists who reclassified 200 "atypical" smears by evaluating PAPNET images only. The interobserver agreement (reliability) of the PAPNET reviewers was computed, and their readings were compared with three standards: the consensus diagnosis of five pathologists who used light microscopy, the detection of cancer-associated human papillomavirus DNA by Southern analysis, and the correlation with diagnoses of biopsy specimens obtained during passive follow-up. The PAPNET reviewers classified 18 to 65% of cases as normal, 25 to 42% as equivocal, and 10 to 55% as abnormal. Unanimous interobserver agreement was achieved in only 24 (13%) cases. Four of the five PAPNET reviewers agreed moderately well with the results of the pathology reference panel. In four of the five PAPNET reviews, classification of cases as abnormal was strongly correlated with the detection of cancer-associated types of human papillomavirus. Consensus PAPNET results of abnormal were predictive of abnormal histologic findings at follow-up. Theoretically, if colposcopy had been performed on all of the women with equivocal or abnormal PAPNET results (based on the consensus of the panel), as much as 95% of biopsy-confirmed lesions could have been detected, but 79% of women would have been referred. Restriction of colposcopy referral to women with definitely abnormal PAPNET readings would have reduced referrals to 31%, but the sensitivity of the triage would have dropped to 51% of biopsy-confirmed lesions.

Biopsy↗
PubMed1997

Immune activation in cervical neoplasia: cross-sectional association between plasma soluble interleukin 2 receptor levels and disease.

In a previous study (Tsukui et al., Cancer Res., 56: 3967-3974, 1996), we observed an inverse association between degree of cervical neoplasia and interleukin (IL) 2 production by peripheral blood mononuclear cells in response to human papillomavirus (HPV) 16 E6 and E7 peptides in vitro. This suggested that a Th1-mediated cellular immune response might be important in host immunological control of HPV infection and that a lack of such a response might predispose to progression of cervical disease. To follow up on these findings, we have conducted a cross-sectional study of women with various degrees of cervical neoplasia to investigate the association between overall immune activation and cervical disease. A total of 235 women were recruited into our study; 120 of these women were participants in our previous study in which IL-2 production in response to HPV-16-specific peptides was measured. The study population included 34 women with invasive cancer, 62 women with high-grade squamous intraepithelial lesions (HSILs), and 105 women with low-grade squamous intraepithelial lesions (LSILs). In addition, 34 cytologically normal women with no past history of squamous intraepithelial lesions despite confirmed HPV-16 infection in the 5 years preceding the study were selected as controls. As our measure of overall immune activation, serum samples obtained from study participants were tested for soluble IL-2 receptor (sIL-2R) level using an ELISA method. The mean sIL-2R levels were found to increase with increasing disease severity (Ptrend = 0.0002). Among cytologically normal, HPV-exposed women, the mean receptor level in serum was 465.8 units/ml compared to 467.6 units/ml among LSIL subjects, 514.9 units/ml among HSIL subjects, and 695.5 units/ml among women with invasive cervical cancer. Similarly, the proportion of women with elevated sIL-2R levels (defined as > or = 450 units/ml) increased with increasing disease severity from 35.2% among normal study subjects to 70.6% among cancer patients (Ptrend = 0.003). Among the subgroup of subjects for whom in vitro IL-2 production in response to HPV-16-specific peptides was measured, we examined the association between in vitro IL-2 production and serum levels of sIL-2R. sIL-2R levels were higher, on average, among those women who were positive in our IL-2 production assay compared to those who were negative, but the differences did not reach statistical significance (P > 0.05). We also observed a trend of increasing sIL-2R level with increasing disease severity both in women who were positive and in women who were negative for our IL-2 production assay, but the trend was only significant among those who were negative for IL-2 production (Ptrend = 0.01). Results from our studies suggest that although the immune system of women with cervical neoplasia is nonspecifically activated as disease severity increases, the ability of those women with HSILs or cancer to mount a Th1-mediated immune response to HPV peptides appears to decrease compared to women with LSILs or normal women infected with HPV. Increased overall activation along with decreased Th1 immune response among women with increasing cervical disease severity might be explained by an increased Th2-mediated immune response, a response that we hypothesize is ineffective in controlling the viral infection and its early cytological manifestations. Future studies should directly assess Th2-mediated responses to confirm this hypothesis. Also, future efforts should be aimed at determining whether the associations observed are causally related to disease progression or an effect of the disease.

Adolescent↗
PubMed1996

Interleukin 2 production in vitro by peripheral lymphocytes in response to human papillomavirus-derived peptides: correlation with cervical pathology.

Human papillomavirus (HPV) is believed to be the major cause of cervical cancer. To investigate whether a cellular immune response, especially a T helper type 1 response, is related to the natural defense against HPV-related cervical lesions, the interleukin 2 response of peripheral blood lymphocytes in vitro to overlapping peptides from HPV-16 E6 and E7 oncoproteins was compared with the degree of cervical cytological abnormality among 140 women in a cross-sectional study. We compared 66 women diagnosed with low-grade squamous intraepithelial lesions (LSIL), 21 with high-grade squamous intraepithelial lesions (HSIL), and 28 with invasive cervical cancer with 25 women who were cytologically normal but previously HPV-16 DNA positive. The fraction showing strong interleukin 2 production against HPV-16 peptides was greatest among cytologically normal women (35%) and declined with increasing disease severity [LSIL] (20%), HSIL, (17%), and cancer patients (7%); X2 test P for the trend = 0.02], whereas the responses against a recall influenza antigen were not significantly different among groups. Our finding suggests that a T helper lymphocyte type 1 response to HPV antigens is associated with disease status. This result may reflect a targeted effect of the disease on immune function or a protective effect of the immune response against disease progression.

Adolescent↗
PubMed1996

The effect of environmental pH on the proton motive force of Helicobacter pylori.

BACKGROUND & AIMS: Responses of the proton motive force (the driving force for protons) in Helicobacter pylori to varying medium pH may explain gastric colonization. The aim of this study was to determine the effect of external pH (pHout) on the proton motive force, the sum of the pH gradient, and the potential difference across the bacterial membrane. METHODS: Intracellular pH (pHin) was measured by bis-carboxyethyl-carboxy fluorescein fluorescence and transmembrane potential difference (PD) by fluorescent quenching of 3,3'-dipropyl thiadicarbocyanine iodide at differing pHout and was correlated with survival. RESULTS: PD was -131 +/- 0.36 mV (n = 3), and pHin was about 8.4 at loading pHout 7.0. PD increased as pHout was increased from 4.0 to 8.0, giving a constant proton motive force of about -220 mV. Outside these limits, PD collapsed irreversibly to zero. Addition of 5 mmol/L urea to weak buffer at pH 3.0 or 3.5 prevented irreversible collapse of PD by elevation of pHout caused by NH3 production. Urea addition to weak buffer at pH 7.0 collapsed the PD as urease activity increased the pHout to about 8.4. Survival was also limited to this range of pHout. CONCLUSIONS: H. pylori survives over the range of pHout where it maintains a proton motive force. The effect of urease activity on pHout, while allowing gastric survival in acidic media, may limit survival in nonacidic media.

Ammonium Chloride↗
PubMed1996

Epidemiologic determinants of seroreactivity to human papillomavirus (HPV) type 16 virus-like particles in cervical HPV-16 DNA-positive and-negative women.

The epidemiologic determinants of seroreactivity to human papillomavirus (HPV) type 16 L1/L2 virus-like particles (VLPs) were assessed separately in HPV-16 DNA-positive and -negative women participating in a nested case-control study of incident cervical neoplasia. Seventy-four women with cervical HPV-16 DNA and 656 cytologically normal HPV-16 DNA-negative subjects were interviewed and tested at two time points for viral DNA and once (at the later time) for VLP seroreactivity. Among subjects who were currently HPV-16 DNA-negative, seroreactivity odds ratios increased from 2.9 for 2-5 male sex partners (vs. 0 or 1) to 5.4 for 6-9 partners and 14.0 for > or = 10. Thus, prior cervical infection may be a major determinant of seroreactivity in HPV-16 DNA-negative women. This trend was not observed in HPV-16 DNA-positive subjects. Seroreactivity was independently associated with oral contraceptive use, particularly in HPV-16 DNA-negative subjects with use for > or = 10 years. Consequently, a possible role for virus-steroid hormone interactions in seroconversion is suggested.

Antibodies, Viral↗
PubMed1995

Accuracy and interlaboratory reliability of human papillomavirus DNA testing by hybrid capture.

Epidemiologists and clinicians wishing to introduce human papillomavirus (HPV) testing into cervical cancer prevention programs need standardized, reliable, and accurate HPV DNA tests that can detect the full spectrum of pathogenic HPV types. The Hybrid Capture System assay from Digene (hybrid capture assay) is a nonradioactive kit designed to detect 14 HPV types in two groups: a mix of 9 high-risk types associated with anogenital cancer (HPV types 16, 18, 31, 33, 35, 45, 51, 52, and 56) and another group of 5 low-risk types associated with condyloma acuminatum (HPV types 6, 11, 42, 43, and 44). The assay yields quantitative data meant to reflect viral concentration. In a study of 199 cervical specimens from women with concurrent Pap smears, we assessed the reliability of the new assay by comparing the hybrid capture assay results from three laboratories. We assessed the accuracy of the hybrid capture assay in comparison with a reference standard of HPV DNA content (multiple testing by several methods in two reference laboratories). We also compared the hybrid capture assay results with the concurrent cytologic diagnoses on the basis of an independent review of each smear by five pathologists. Pairwise interlaboratory agreement rates on HPV positivity for either high-risk or low-risk types ranged from 87 to 94%, and kappa values ranged from 0.61 to 0.83. Among specimens positive for high-risk types (the most important clinical outcome), the interlaboratory correlations of the quantitative data ranged from 0.60 to 0.90. Test results from all three laboratories were strongly associated with those of the HPV DNA reference standard and with the concurrent cytopathologic diagnoses. The most common errors were sporadic, apparently false-positive results.

Cervix Uteri↗
PubMed1994

Effects of antisecretory agents on parietal cell structure and H/K-ATPase levels in rabbit gastric mucosa in vivo.

The effect of inhibition of acid secretion on parietal cell morphology and the concentration of H,K-ATPase alpha-subunit protein was determined by electron microscopy and western blotting. Omeprazole or famotidine alone or in combination were used. Control animals showed a morphological stimulation index (0 = resting, 1.0 = fully stimulated) of 0.60; omeprazole treatment (1 mg/kg, twice a day) resulted a stimulation index of 0.63, famotidine injection (20 mg/kg twice a day) an index of 0.11, famotidine infusion (0.2 mg/hr) for five days an index of 0.38, and the combination of omeprazole and famotidine injection twice a day gave an index of 0.02. No change in the frequency of degenerating or damaged parietal cells was observed in any of the groups. In control animals, the number of lysosomes was 0.9/cell, with famotidine 1.8 and with omeprazole 5.6/cell. H/K-ATPase levels fell by about 25% with omeprazole and rose by about 23% with famotidine.

Animals↗
PubMed1994

A seroepidemiologic study of HPV infection and incident cervical squamous intraepithelial lesions.

The seroepidemiology of genital human papillomavirus (HPV) and incident cervical squamous intraepithelial lesions (SIL) was studied in subjects selected from a large cohort monitored for the development of SIL. Serum IgG and IgA responses to 10 epitopes derived from HPV were measured in 21 incident cases of SIL and 56 matched controls. Cases showed elevated antibody (i.e., IgG and/or IgA) seroprevalence to 245:16, a peptide antigen derived from the E2 open reading frame of HPV 16 (OR = 5.76; 95% CI: 1.24, 26.81). The type of HPV DNA detected in cervical lavage specimens had no effect on this relationship. Multivariate analysis also showed that IgG to 245:6, an analogous peptide derived from HPV 6, was negatively associated with SIL (OR = 0.12; 95% CI: 0.02, 0.77). No other antibody responses tested were associated with SIL. Furthermore, no antibody responses were positively associated with detection of HPV DNA in women without SIL. We conclude that incident SIL is positively associated with antibody to an epitope derived from the E2 region of HPV 16, and negatively associated with antibody to an analogous peptide derived from HPV 6. The seroepidemiology of incident SIL appears different from that of cervical HPV infection in the absence of SIL.

Adult↗
PubMed1994

Toward objective quality assurance in cervical cytopathology. Correlation of cytopathologic diagnoses with detection of high-risk human papillomavirus types.

Using The Bethesda System, five pathologists independently diagnosed 200 smears that originally had been classified as "atypical," and the results were correlated with concurrent detection of human papillomavirus (HPV) DNA by Southern analysis and by polymerase chain reaction amplification. The smears were reclassified as benign reactive changes (negative), atypical squamous cells of undetermined significance, or squamous intraepithelial lesion (SIL). Exact five-way cytologic agreement was achieved in only 29% of smears, and no slide was diagnosed as atypical squamous cells of undetermined significance by all reviewers. The detection of high-risk types of HPV correlated strongly with the likelihood of a diagnosis of squamous intraepithelial lesion. High-risk HPV types were detected in approximately 60% of smears reclassified as squamous intraepithelial lesion compared with 30% of those reclassified as atypical squamous cells of undetermined significance and 10% of negative smears (P < .001). Every smear unanimously diagnosed by the panel as squamous intraepithelial lesion was associated with detectable HPV DNA, mainly of high-risk types. Low-risk HPV DNA types were found with similar frequency in all diagnostic categories assigned by the reviewers. Based on the consistent relation between high-risk HPV detection and diagnoses according to the Bethesda System, the authors conclude that HPV testing may have an important role in quality assurance in cervical cytopathology.

Blotting, Southern↗
PubMed1994

Persistence of type-specific human papillomavirus infection among cytologically normal women.

Determinants of genital human papillomavirus (HPV) persistence in 393 women initially cytologically normal were investigated by testing them for HPV DNA twice over a median interval of 14.9 months. At each visit, interview information was obtained and a cervicovaginal lavage sample was collected for polymerase chain reaction-based HPV testing. Twenty-six percent of the women were HPV-positive at the first sampling. Data on HPV type was available for 86 HPV-positive women (84%); 35 of these women (41%) had persistent type-specific HPV detection. Persistence decreased with time between samplings. Women aged > or = 30 years had a higher percentage of persistence (65%) than those < or = 24 years (32%, P = .02). The percentage of persistence was higher among women infected with HPV types known to be cancer-associated (45%) than among those infected with other types (24%, P = .11). These findings were independent of each other and of timing between samplings. Although based on a prevalent cohort, these results are concordant with previous suggestions that HPV infection is usually transient and that cervical cancer may arise from within the subset of women with persistent HPV infection.

Adolescent↗
PubMed1994

Gastrin effects on isolated rat enterochromaffin-like cells in primary culture.

The hormone gastrin stimulates acid secretion by releasing histamine from gastric enterochromaffin-like (ECL) cells and induces ECL cell proliferation in vivo. This study uses a > 90% pure ECL cell preparation in culture to compare gastrin effects on histamine release, histidine decarboxylase (HDC) activity, and DNA synthesis. Gastrin and the cholecystokinin octapeptide (CCK-8, nonsulfated) induced histamine release from ECL cells (24-96 h of primary culture) within 5 min of incubation [concentration eliciting 50% of maximal response (EC50), 4 and 2 x 10(-11) M, respectively]. The CCK-B antagonist L-365,260 inhibited this effect [concentration inhibiting 50% of maximal response (IC50), 2 x 10(-8) M], whereas the CCK-A antagonist L-364,718 (10(-8) M) and the tyrosine kinase inhibitor genistein (10(-4) M) had no effect. Histamine release was associated with a biphasic elevation of intracellular Ca2+. Gastrin stimulated HDC activity two- to threefold after 60 min of incubation (EC50, 10(-10) M). Gastrin also increased DNA synthesis in ECL cells, with an EC50 of 1.7 x 10(-12) M as measured by the incorporation of 5-bromo-2'-deoxyuridine (BrdU). Positive nuclear immunostaining increased two- to threefold in up to 20% of ECL cells after 48-96 h of incubation. This effect was inhibited by L-365,260 (IC50, 5 x 10(-9) M) and by genistein (10(-4) M) but was not altered by L-364,718 (10(-8) M). The antisecretory drugs omeprazole, lansoprazole, and pantoprazole did not affect BrdU incorporation in isolated ECL cells. In conclusion, acute and chronic gastrin effects on the ECL cell are mediated via CCK-B receptors but differ in apparent receptor affinity and signal transduction pathways.

Animals↗
PubMed1993

Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia.

BACKGROUND: Experimental studies have provided strong evidence that human papillomavirus (HPV) is the long-sought venereal cause of cervical neoplasia, but the epidemiologic evidence has been inconsistent. PURPOSE: Given improvements in HPV testing that have revealed a strong link between sexual activity history and cervical HPV infection, we conducted a large case-control study of HPV and cervical intraepithelial neoplasia (CIN) to evaluate whether sexual behavior and the other established risk factors for CIN influence risk primarily via HPV infection. METHODS: We studied 500 women with CIN and 500 control subjects receiving cytologic screening at Kaiser Permanente, a large prepaid health plan, in Portland, Ore. The established epidemiologic risk factors for CIN were assessed by telephone interview. We performed HPV testing of cervicovaginal lavage specimens by gene amplification using polymerase chain reaction with a consensus primer to target the L1 gene region of HPV. Unconditional logistic regression analysis was used to estimate relative risk of CIN and to adjust the epidemiologic associations for HPV test results to demonstrate whether the associations were mediated by HPV. RESULTS: The case subjects demonstrated the typical epidemiologic profile of CIN: They had more sex partners, more cigarette smoking, earlier ages at first sexual intercourse, and lower socioeconomic status. Statistical adjustment for HPV infection substantially reduced the size of each of these case-control differences. Seventy-six percent of cases could be attributed to HPV infection; the results of cytologic review suggested that the true percentage was even higher. Once HPV infection was taken into account, an association of parity with risk of CIN was observed in both HPV-negative and HPV-positive women. CONCLUSION: The data show that the great majority of all grades of CIN can be attributed to HPV infection, particularly with the cancer-associated types of HPV. IMPLICATIONS: In light of this conclusion, the investigation of the natural history of HPV has preventive as well as etiologic importance.

Adolescent↗