On Doctoring MEDLINE searches, with reference librarian comments, March 2000

The question was

What is the efficacy and benefits of HPV-DNA testing as compared with current diagnostic tools, such as colposcopy and cone biopsy?

1     Dna probes, hpv/du [Diagnostic Use]    results=83   
2     limit 1 to (local holdings and human and yr=1991-2000)    results= 41   
3     limit 2 to (local holdings and human and english language    results= 6   
and yr=1996-2000)
4     limit 3 to (human and english language)    results= 6   
5     2    results= 41   
6     limit 5 to (human and english language and yr=1996-2000)    results= 6   

Reference Librarian comments

Interesting search! You and Ovid got to the most-appropriate subject heading for this: "dna probes, hpv" -- and then you chose "diagnostic use." That's hard to beat, as a strategy. I think you knew you were done with that perfect Set #1, and then you just started applying "limits" to get fewer articles to wade through. Fine.

But, I decided to fuss around with this search, because the concept was new to me. I replicated what YOU did, and then went off on various tangents.

I'll show you my strategy (below), and the first 10 of the 49 results I got.

Medline 1991 to January 2000

#
Search History
Results
1
exp dna probes, hpv/du
83
2
exp dna, viral/an
6578
3
exp papovaviridae infections/di
673
4
2 and 3
134
5
1 or 4
213
6
hpv dna.ti.
101
7
5 or 6
306
8
exp comparative studies/
386774
9
7 and 8
52
10
exp *Colposcopy/
314
11
"CONE BIOPSY".mp.
167
12
7 and 10
6
13
7 and 11
1
14
12 or 13
7
15
9 or 14
57
16
limit 15 to (human and english language)
49

<1>
AN 99242132
AU Hutchinson ML. Zahniser DJ. Sherman ME. Herrero R. Alfaro M. Bratti MC.
Hildesheim A. Lorincz AT. Greenberg MD. Morales J. Schiffman M.
IN Women & Infants Hospital, Brown University, Providence, Rhode Island
02905-2401, USA.
TI Utility of liquid-based cytology for cervical carcinoma screening: results
of a population-based study conducted in a region of Costa Rica with a high
incidence of cervical carcinoma.
SO Cancer. 87(2):48-55, 1999 Apr 25.
LM Pre-1993 Dana; 1993-dateMFHSL;for Web access-check catalog
AB BACKGROUND: In a study using a split-sample design, liquid-based cytology
(ThinPrep Processor, Cytyc Corporation, Boxborough, MA) was compared with the
conventional Papanicolaou (Pap) smear in Guanacaste, Costa Rica. The study
provides the first population-based comparison of the ThinPrep screening
technology and includes "gold standard" measures of diagnostic accuracy.
METHODS: The population-based study was performed among over 8000 women
residing in a Costa Rican province with a high incidence of cervical
carcinoma. Conventional smears were prepared and diagnosed in Costa Rica,
while the residual material on the sampling device was collected into a
liquid preservative and shipped to the U.S., where ThinPrep cytologic slides
were prepared and diagnosed. Cytologic diagnoses based on the two techniques,
categorized according to the Bethesda System, were compared with a "gold
standard" final case diagnosis for each patient, also based on Bethesda
terminology, that reflected an integrated interpretation of all available
data, including cytology, histology, and cervicography. Results were also
compared with the results of HPV DNA
detection (Hybrid Capture, Digene Corporation, Silver Spring, MD). RESULTS:
ASCUS was the threshold for colposcopy referral. There were
significantly more women referred according to this threshold with the
ThinPrep slide (12.7%) than with the conventional smear (6.7%, P<0.001).
Compared with the final case diagnosis, referral by ThinPrep slides detected
92.9% of cases with high grade squamous intraepithelial lesions (HSIL) and
100% of carcinoma cases. Smears detected 77.8% of HSIL and 90.9% of
carcinomas. Thus, ThinPrep cytology was significantly more sensitive in the
detection of HSIL and cancer (McNemar test, P<0.001). Adjudication of cases
in which the ThinPrep and smear diagnoses disagreed, using the final case
diagnoses and the HPV DNA test results as
reference standards, suggested that the ThinPrep method was detecting
additional true SIL as opposed to false-positives. CONCLUSIONS: In a
population-based study of high risk women, ThinPrep cytology demonstrated
significantly increased sensitivity for detecting HSIL and carcinoma, with a
concurrent significant increase in colposcopy referrals.

<2>
AN 99150438
AU Harnish DG. Belland LM. Scheid EE. Rohan TE.
IN Departments of Pathology and Biology, McMaster University, 1200 Main Street
West, Hamilton, Ontario, L8N 3Z5, Canada. harnishd@fhs.csu.mcmaster.ca
TI Evaluation of human papillomavirus-consensus primers for
HPV detection by the polymerase chain reaction.
SO Molecular & Cellular Probes. 13(1):9-21, 1999 Feb.
LM Some issues available on Web. Check catalog for details.
AB Cervical cancer is one of the most frequently found cancers in women and
appears to have a viral aetiology. Substantial evidence
points to the human papillomaviruses (HPV) as the infectious
agents and there is considerable interest in identifying and accurately
typing the viruses. Since HPVs now comprise more than 100
different HPV types, the polymerase chain reaction (PCR) has
been the preferred methodology for virus identification and typing on
isolated DNA. In that context, five commonly employed PCR
consensus primers have been evaluated for the detection and typing of
HPV. The five consensus primer pairs were derived from the
consensus sequences of either the L1 and E1 open reading frames. All primers
exhibited approximately equal sensitivity, as defined by the ability to
detect HPV DNA, on a series of standard
HPV DNA-containing preparations. However,
the five primer pairs performed differently on 24
HPV-positive and 34 HPV-negative samples
obtained from cervical scrapes which had been typed by type-specific PCR for
HPV 6/11, 16, 18 and 33. The values for agreement between
identification of samples by a HPV type-specific PCR and the
consensus primer PCR were 78, 84, 91, 93 and 98%. Three samples, which were
positive with only one of the five consensus primer pairs and were negative
with the PCR for HPV types 6/11, 16, 18 and 33, contained
other HPV sequences or HPV-related
sequences as determined by DNA sequence analysis. To our
knowledge, this report represents the first extensive comparison of five
different consensus primers in a polymerase chain reaction for the detection
of HPV. Our results suggest that PCR typing for human
papillomaviruses requires more than one consensus primer pair to identify all
HPV-infected samples. Copyright 1999 Academic Press.

<3>
AN 99100247
AU Kubota T. Ishi K. Suzuki M. Utsuno S. Igari J.
IN Department of Obstetrics and Gynecology, Juntendo University, Chiba, Japan.
TI Usefulness of hybrid capture HPV DNA assay
as a diagnostic tool for human papillomavirus infection.
SO Kansenshogaku Zasshi - Journal of the Japanese Association for Infectious
Diseases. 72(11):1219-24, 1998 Nov.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.
AB The purpose of this study was to determine the usefulness of the hybrid
capture HPV DNA assay, a new nonradioactive
solution hybridization assay, as a diagnostic tool for human papillomavirus
infection. In a total of 234 women, samples for the hybrid capture assay and
polymerase chain reaction (PCR) assay were obtained by wiping a swab across
the cervix and external os (either a Dacron swab or a cotton swab was used).
The papanicolaou smear test (Pap smear) was carried out on all 234 women.
Tissue samples for biopsy were obtained by
colposcopy from 118 of the women. Fisher exact test was used
for statistical analyses. Using the hybrid capture assay,
HPV DNA of high- and
intermediate-oncogenic-risk type was detected in 23 (13.9%) of 166 samples
from women with Pap smear Class I or II, and 48 (70.6%) of 68 with Pap smear
Class III, IV or V (p < 0.0001). The HPV
DNA type was detected in 18 (29.0%) of 62 samples from those
with no evidence of cervical intraepithelial neoplasia and 44 (78.6%) of 56
with cervical intraepithelial neoplasia or squamous cell carcinoma (p <
0.0001). Correlation of the test results between the hybrid capture test and
PCR was determined by using the 217 samples in which both test results were
available (PCR test results were not obtainable in 17 samples. When PCR is
set as a gold standard, the hybrid capture test has high sensitivity (74.6%)
and specificity (92.7%). These findings suggest that the hybrid capture
HPV DNA assay is a useful method for
diagnosing HPV infection in the clinic.

<4>
AN 99031518
AU Khurshid A. Kazuya N. Hanae I. Manabu I.
IN Department of Pathology, Fukui Medical School, Japan.
TI Infection of human papillomavirus (HPV) and Epstein-Barr
virus (EBV) and p53 expression in human esophageal carcinoma.
SO JPMA - Journal of the Pakistan Medical Association. 48(5):138-42, 1998 May.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.
AB To clarify the role of high risk human papillomavirus (HPV
16, 18 and 33) and Epstein-Barr virus (EBV) infection in esophageal
carcinogenesis in relation to expression of mutated p53 antioncogene, we used
PCR to amplify DNA sequences of these viruses and
immunohistochemistry to detect p53 expression in formaline-fixed, paraffin
embedded blocks including 12 normal esophageal and 27 esophageal carcinoma
specimens. HPV and EBV DNA were found in
25% and 0% of normal esophageal tissues and in 63% and 7% of esophageal
carcinoma specimens, respectively. p53 expression was shown in 59% of
esophageal carcinoma specimens only. HPV infection rate was
significantly higher in specimens from carcinoma cases as compared with
normal esophageal tissue obtained from cases without carcinoma. No
correlation was found between p53 expression and/or the presence of
viral DNA (HPV/EBV) in
regard to the age and sex of the patient, histological grade, histological
stage, depth of invasion, lymph node involvement, distant metastasis and the
location of the tumors, p53 expression was almost equally distributed between
HPV positive and negative carcinoma cases. Our results
suggest that most of the esophageal carcinomas are associated with
HPV infection and p53 mutations and there is no inverse
correlation between HPV and infection and expression of p53
in esophageal carcinoma.

<5>
AN 99009283
AU Fait G. Daniel Y. Kupferminc MJ. Lessing JB. Niv J. Bar-Am A.
IN Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv,
Israel.
TI Does typing of human papillomavirus assist in the triage of women with
repeated low-grade, cervical cytologic abnormalities? [see comments].
CM Comment in: Gynecol Oncol 1998 Sep;70(3):317-8
SO Gynecologic Oncology. 70(3):319-22, 1998 Sep.
LM Print holdings at DANA. For Web access, check catalog.
AB OBJECTIVE: To evaluate the ability of testing for high-risk human
papillomavirus (HPV) using the hybrid capture technique to
detect cervical intraepithelial neoplasia (CIN) in patients with repeated
low-grade cervical cytologic abnormalities and an adequate and normal
colposcopy. METHODS: Hybrid capture testing and LEETZ were
performed on 166 women with repeated low-grade cervical cytologic
abnormalities who were referred for colposcopy which was to
be adequate and normal. RESULTS: A highly significant correlation (P <
0.0001) was found between a positive test for high-risk HPV
types and the finding of CIN II,III. In 67 women with atypical squamous cells
of undetermined significance on repeated cytologic studies,
a positive test for high-risk HPV types had a sensitivity
and specificity of 90 and 96.5%, respectively, for detecting CIN II,III. In
99 patients with low-grade squamous intraepithelial lesions found on repeated
cytologic study, a positive test for high-risk HPV types
identified all patients as having CIN II,III on cone
biopsy (sensitivity, 100%), with a specificity of 86.4%.
Restriction of tissue sampling to women who were positive for high-risk
HPV types would have reduced the number of tissue samplings
performed to 20.4%, while identifying 20 of 21 patients with
biopsy-confirmed CIN II, III. CONCLUSION: A positive hybrid
capture test for high-risk HPV types is highly sensitive and
specific for detecting CIN II,III in patients with repeated low-grade
cervical cytologic abnormalities and an adequate and normal
colposcopy and may be used in the triage of these women
before performing tissue sampling. Copyright 1998 Academic Press.

<6>
AN 98148298
AU Ferris DG. Wright TC Jr. Litaker MS. Richart RM. Lorincz AT. Sun XW.
Borgatta L. Buck H. Kramer L. Rubin R.
IN Department of Family Medicine, Medical College of Georgia, Augusta 30912,
USA.
TI Triage of women with ASCUS and LSIL on Pap smear reports: management by
repeat Pap smear, HPV DNA testing, or
colposcopy? [see comments].
CM Comment in: J Fam Pract 1998 Feb;46(2):121-4
SO Journal of Family Practice. 46(2):125-34, 1998 Feb.
LM Pre-1993 at Dana,1993-date at MFHSL.
AB BACKGROUND: The purpose of this study was to determine the efficacy of a
repeat Papanicolaou (Pap) smear and the Hybrid Capture tube-based (HCT)
HPV DNA test for detecting cervical
intraepithelial neoplasia (CIN) grade 2 or 3 in women with recent atypical
squamous cells of undetermined significance (ASCUS) or low-grade squamous
intraepithelial lesion (LSIL) Pap smear reports. METHODS: Women with a recent
Pap smear report of ASCUS (n = 169) or LSIL (n = 110) had a repeat Pap smear,
sampling of the cervix for HCT HPV DNA
assay and a colposcopy examination. Data were evaluated
using three different triage thresholds for colposcopy
examination: a repeat Pap smear of persistent ASCUS or more severe dysplasia,
a finding of persistent LSIL or more severe dysplasia, and a carcinogenic
HPV test result. RESULTS: The sensitivity, specificity, and
positive and negative predictive values for detecting CIN 2/3 were 70%, 45%,
7%, and 96% for a repeat Pap smear using an ASCUS-positive threshold and 20%,
86%, 8%, and 94% for a repeat Pap smear using an LSIL-positive threshold,
respectively, when women with an initial ASCUS Pap smear were considered.
HPV testing for carcinogenic viruses alone or in combination
with a repeat Pap smear (using ASCUS as a positive threshold) yielded results
of 50%, 67%, 9%, and 96%, respectively, and 70%, 37%, 7%, and 95%,
respectively, for detecting CIN 2/3. In women with an initial LSIL Pap smear,
respective values for detecting CIN 2/3 by a repeat Pap smear with an ASCUS
threshold were 92%, 26%, 14%, and 96%, and for an LSIL threshold 23%, 64%,
8%, and 86%, respectively. Hybrid Capture HPV testing alone
or in combination with a repeat Pap smear yielded 69%, 43%, 14%, and 91%,
respectively, and 100%, 21%, 14%, and 100%, respectively. CONCLUSIONS: A Pap
smear triage threshold restricted to LSIL or more severe dysplasia for women
with prior ASCUS or LSIL Pap smear results was clearly ineffective for
detecting high-grade cervical precancerous lesions. In contrast, when the
repeat Pap smear triage threshold was expanded to include persistent ASCUS as
abnormal, 83% of the women with CIN 2/3 were detected. Detection of
carcinogenic HPV DNA using the HCT test was
almost as sensitive for detecting CIN 2/3 as a solitary repeat Pap smear
using an ASCUS or more severe positive threshold. Combining the
HPV test with a repeat Pap smear did not significantly
improve the sensitivity of cytology for detecting high-grade CIN. This study
suggests that women with ASCUS and particularly LSIL Pap smears should be
referred for a colposcopy examination until better triage
methods become available.

<7>
AN 97388454
AU Sigurdsson K. Arnadottir T. Snorradottir M. Benediktsdottir K.
Saemundsson H.
IN The Icelandic Cancer Society, The Cancer Detection Clinic, Reykjavik.
krabb@krabb.is
TI Human papillomavirus (HPV) in an Icelandic population: the
role of HPV DNA testing based on hybrid
capture and PCR assays among women with screen-detected abnormal Pap smears.
SO International Journal of Cancer. 72(3):446-52, 1997 Jul 29.
LM Print holdings at DANA. For Web access, check catalog.
AB This study was based on 358 cases with abnormal smears referred for
colposcopy and HPV DNA
testing. We analysed: 1) the frequency of different grades of cyto- and
histopathologic findings; 2) the frequency and relative amount of
HPV DNA with the hybrid capture assay (HCA)
in swabs, and the frequency of HPV with PCR in swabs (-S)
and biopsies (-B); and 3) the frequency of HPV types
according to the grade of the cyto- and histopathologic findings. Of all
cases, 95% were positive with all HPV tests combined. The
HCA (HPV: 16, 18, 31, 33, 35, 45, 51, 52 and 56) and the
PCR-S and PCR-B (HPV: 16, 18, 31, 33 and 35) tests for
high-risk HPV exhibited sensitivities of 57%, 56% and 48%,
respectively. The high-grade smears and the high-risk PCR-S
HPV had about 80% sensitivity for histologic high-grade
lesions compared with around 70% for HCA and the PCR-B. Combining the
high-grade smears and the high-risk HPV increased the
sensitivity to 93-96%. Among the cervical intraepithelial neoplasia I (CIN I)
and the atypical squamous cells of undetermined significance (ASCUS) smears
the sensitivity of high-risk HPV for high-grade histologic
lesions was 63% for the HCA and 79% for the PCR-S. No correlation was found
between the relative amount of HPV DNA
detected by HCA and the grade of cyto- and histological lesions. We conclude
that the results strongly indicate that HCA is less sensitive than PCR in the
diagnosis of high-risk HPV, that swabs are more sensitive
than biopsies as a sampling method, that high-risk HPV and
high-grade smears are complementary for the diagnosis of high-grade
histologic lesions and that the present role of HPV testing
in screening could be limited to identifying women with low-grade smears and
koilocytotic or low-grade colposcopic biopsies that are at risk of concealing
or developing high-grade histologic lesions.

<8>
AN 97305966
AU Qu W. Jiang G. Cruz Y. Chang CJ. Ho GY. Klein RS. Burk RD.
IN Department of Microbiology & Immunology, Albert Einstein College of
Medicine, Bronx, New York 10461, USA.
TI PCR detection of human papillomavirus: comparison between MY09/MY11 and
GP5+/GP6+ primer systems.
SO Journal of Clinical Microbiology. 35(6):1304-10, 1997 Jun.
LM Dana. Incomplete holdings, check catalog.
AB Human papillomavirus (HPV) is an etiologic agent of
cervical cancer and is the most common sexually transmitted disease in women.
PCR amplification of HPV genomes is the most sensitive
method for the detection of cervicovaginal HPV. We have
compared the two most commonly used PCR primer sets, MY09/MY11 (MY-PCR) and
GP5+/GP6+ (GP+-PCR), for the detection of HPV
DNA in cervicovaginal lavage samples from 208 women.
Oligonucleotide probes for 39 different HPV types were used.
Both primer sets amplified a wide spectrum of HPV genotypes
and detected similar overall prevalences of 45% (94 of 208) and 43% (89 of
208), respectively. The MY-PCR system detected 27 of 30 (90%) samples with
multiple HPV types, whereas the GP+-PCR system detected 14
of 30 (47%) samples with multiple HPV types. Differences in
the detection of HPV types 35, 53, and 61 were noted between
the two primer systems. Serial dilution of plasmid templates indicated a
3-log decrease in the amplification of HPV type 35 by MY-PCR
and HPV types 53 and 61 by GP+-PCR. These results indicate
that although the MY-PCR and GP+-PCR identified nearly equivalent prevalences
of HPV in a set of clinical samples, differences in the
detection of specific types and infections with multiple
types were found. Differences in the sensitivities and characteristics of the
PCR systems for the detection of HPV within clinical samples
should be considered when comparing data between studies
and/or in designing new studies or clinical trials.

<9>
AN 97357916
AU Olsen AO. Dillner J. Gjoen K. Magnus P.
IN Department of Population Health Sciences, National Institute of Public
Health, Oslo, Norway.
TI Seropositivity against HPV 16 capsids: a better marker of
past sexual behaviour than presence of HPV
DNA.
SO Genitourinary Medicine. 73(2):131-5, 1997 Apr.
LM Dana. Incomplete holdings, check catalog.
AB OBJECTIVES: To assess if seropositivity to human papillomavirus type 16
capsids is a better marker of sexual history than the presence of
HPV DNA. STUDY DESIGN: A population based
age stratified random sample of 234 Norwegian women (mean age 32.8 years,
range 20-44) was examined for HPV serum antibodies, cervical
HPV DNA, cytology and age in relation to
sexual behaviour. RESULTS: Neither age nor age at first sexual intercourse
was associated with HPV 16 antibodies. Adjusted ORs for 4-5;
6-10 and > 10 versus 0-1 lifetime sexual partners, were 13.1 (95% CI
1.5-110.8), 8.2 (1.0-69.6) and 10.5 (1.2-94.0) for HPV 16
seropositivity, respectively; and 2.6 (0.2-27.8), 3.4 (0.4-31.7) and 4.1
(0.4-42.8) for HPV 16 DNA positivity,
respectively. CONCLUSION: Seropositivity to HPV 16 capsids
is positively associated with the number of sexual partners, suggesting that
HPV 16 is predominantly sexually transmitted. The fact that
serology had a stronger association with number of sexual partners than
viral DNA suggests that seroreactivity is a
better measure of lifetime history of HPV infection.

<10>
AN 97245241
AU Mansat-Krzyzanowska E. Dantal J. Hourmant M. Litoux P. Soulillou JP.
Dreno B.
IN Department of Dermatology, Hotel-Dieu, Nantes, France.
TI Frequency of mucosal HPV DNA detection
(types 6/11, 16/18, 31/35/51) in skin lesions of renal transplant patients.
SO Transplant International. 10(2):137-40, 1997.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.
AB Human papillomaviruses (HPV) probably play a role in the
development of skin cancer in renal transplant recipients. Since some mucosal
HPV are strongly related to cervical cancer, we compared the
frequency of HPV DNA detection (mucosal
types 6/11, 16/18, and 31/33/51) in skin cancer of renal transplant
recipients (21 lesions) with that in normal subjects without immunodeficiency
(21 lesions) and studied the frequency of these same HPV in
benign lesions of renal transplant recipients (34 lesions) and normal
subjects (30 lesions). An in situ hybridization technique employing cold
biotin probes was used. HPV DNA was not
significantly (P = 0.095) more frequent in malignant skin cancer in renal
transplant recipients (42.9%) than in normal subjects (19.04%), but was
significantly more frequent in benign lesions in renal transplant recipients
(32.4%) than in controls (10%; P < 0.05). These results on a limited number
of skin lesions do not allow one to confirm the predominant role of mucosal
HPV in the development of skin cancer in renal transplant
recipients. HPV interaction with other factors related to
the immunosuppressive state may play a role.