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

The question was

What is the connection b/w HPV and occurances of anal cancer?

1    (anal cancer and HPV).mp. [mp=title, abstract, registry    results=20   
number word, mesh subject heading]

Reference Librarian comments

Searching the Ovid Medline will be much better if you separate the concepts into discreet elements. Articulate the question in your mind like this:

a) I'll make a big set of all articles on HPV
b) then I'll make a big set of all articles on anal cancer
c) then I'll get the "intersection" of those two sets
d) then, depending on how much I get in set #3, I'll think of limiting by language, age, human, etc.

Here's my strategy, below...

Medline 1991 to January 2000

#
Search History
Results
1
exp *Papillomavirus, human/
2986
2
exp *Anus neoplasms/
699
3
1 and 2
46
4
limit 3 to (human and english language)
42

<1>
AN 20009019
AU Frisch M. Biggar RJ.
TI Aetiological parallel between tonsillar and anogenital squamous-cell
carcinomas [letter].
SO Lancet. 354(9188):1442-3, 1999 Oct 23.
LM Dana(complete) &MFHSL(1990-date);also Web,check catalog .
AB Patients with human papillomavirus (HPV)-associated
anogenital cancers had a 4.3-fold increased risk of tonsillar squamous-cell
carcinoma. These cancer types also have histopathological and molecular
biological similarities. Thus HPV may be aetiologically important in
tonsillar carcinogenesis.

<2>
AN 99377504
AU Lacey HB. Wilson GE. Tilston P. Wilkins EG. Bailey AS. Corbitt G.
Green PM.
IN Department of Genito-Urinary Medicine, North Manchester Health Care Trust.
TI A study of anal intraepithelial neoplasia in HIV positive homosexual men.
SO Sexually Transmitted Infections. 75(3):172-7, 1999 Jun.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.
AB OBJECTIVES: To determine the prevalence of high grade anal intraepithelial
neoplasia (HGAIN), the value of anal cytology in screening for HGAIN, and the
characterisation of epidemiological factors and human
papillomavirus (HPV) types. METHODS: Prospective cohort study of HIV positive
homosexual men. Subjects were interviewed, underwent STD, anal cytological,
and HPV screening at enrolment and at subsequent follow up visits with
anoscopy and biopsy at the final visit. 57 enrolled, average CD4 count 273 x
10(6)/l (10-588); 41 completed the cytological surveillance over the follow
up period (181 visits, average follow up 17 months), 38 of these had anoscopy
and anal biopsy. RESULTS: Oncogenic HPV types were detected in 84% and high
grade dyskaryosis in 10.5% (6/57) at enrollment. There was a 70% incidence of
high grade dyskaryosis during follow up in patients with negative/warty or
low grade dyskaryosis at enrollment. Anoscopy correlated with histology in
high grade AIN lesions (sensitivity 91%, specificity 54%) and cytology was
78% sensitive (18/23) for HGAIN on biopsy. CONCLUSIONS: AIN and infection
with multiple oncogenic HPV types are very common among immunosuppressed HIV
positive homosexual men. Apparent progression from low to high grade
cytological changes occurred over a short follow up period, with no cases of
carcinoma. All 23 cases of HGAIN were predicted by cytology and/or anoscopy.
Future studies focusing on the risk of progression to carcinoma are needed
before applying anal cytology as a screening tool for AIN in this population.

<3>
AN 99301212
AU Indinnimeo M. Cicchini C. Stazi A. Giarnieri E. French D. Limiti MR.
Ghini C. Vecchione A.
IN First Department of Surgery, University La Sapienza, Rome, Italy.
TI Human papillomavirus infection and p53 nuclear
overexpression in anal canal carcinoma.
SO Journal of Experimental & Clinical Cancer Research. 18(1):47-52, 1999 Mar.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.
AB The product of HPV E6 and E7 genes is able to inactivate both the p53 and
pRb proteins. The aim of this study was to evaluate the correlation among
anal HPV infection and nuclear p53 overexpression. The Authors evaluated HPV
DNA by PCR and p53 nuclear expression by immunohistochemistry in 12
cloacogenic and 6 squamocellular carcinoma. HPV DNA was detected in 71.4% of
the squamocellular tumors and in 57.1% of the cloacogenic tumors. In
squamocellular tumors HPV types 31-33 and 16 were found; in cloacogenic
tumors type 16 alone was detected. Nuclear accumulation of p53 was found to
be associated with the presence of HPV. There was no significant difference
in parietal infiltration, lymph nodes involvement and prognosis between
HPV+p53+ patients and HPV-p53- patients. Tumor aggressiveness is likely to be
enhanced by factors other than HPV infection and p53 overexpression.

<4>
AN 99137513
AU Frisch M. Fenger C. van den Brule AJ. Sorensen P. Meijer CJ. Walboomers
JM. Adami HO. Melbye M. Glimelius B.
IN Department of Epidemiology Research, Danish Epidemiology Science Center,
Statens Serum Institut, Copenhagen S.
TI Variants of squamous cell carcinoma of the anal canal and perianal skin and
their relation to human papillomaviruses.
SO Cancer Research. 59(3):753-7, 1999 Feb 1.
LM Pre-1993 at Dana,1993-date at MFHSL.
AB High-risk types of human papillomaviruses (hrHPVs) may be a
necessary cause in cervical cancer and in some subtype of anal, vulvar, and
penile cancers. Large studies aimed at characterizing hrHPV-associated and
non-hrHPV-associated subtypes of anal carcinomas are, however, lacking. We
searched for human papillomavirus type 16 and 13 other
hrHPVs in tumor tissue by PCR and performed a systematic histological
evaluation of specimens from 386 patients with anal cancer (86% invasive; 302
women and 84 men). Cancers in women and homosexual men were more often hrHPV
positive (P < 0.01) and located in the anal canal (P < or = 0.01) than were
cancers in heterosexual men. In both women and men, anal canal cancers
contained hrHPV clearly more often than did perianal skin cancers, and
increasing hrHPV positivity was seen with higher localization in the anal
canal. Indeed, 95 and 83% of cancers involving the anal canal in women and
men, respectively, were hrHPV positive versus 80 and 28% of perianal skin
cancers (P-trend < 0.001). Basaloid feature, adjacent anal intraepithelial
neoplasia, poor or absent keratinization, and a predominance of small or
medium neoplastic cells were all strongly positively associated with hrHPV
status. Like cancer of the uterine cervix, the development of cancer of the
anal canal may require infection with hrHPV, whereas a dual etiology of
perianal skin cancers bears parallels to vulvar and penile cancers.

<5>
AN 99108600
AU Caruso ML. Valentini AM.
IN Department of Histopathology, I.R.C.C.S. S. de Bellis, Castellana Grotte,
Bari, Italy.
TI Immunohistochemical detection of p53 protein in anogenital lesions and its
relationship with HPV status.
SO Anticancer Research. 18(6A):4097-100, 1998 Nov-Dec.
LM Dana. Incomplete holdings, check catalog.
AB The p53 tumour suppressor protein can be rendered ineffective by mutations
in the p53 gene or by interactions with proteins of DNA-transforming viruses,
including Human Papillomaviruses (HPVs). Our aim was to
determine whether the inactivation of p53, caused by a mutation of gene
itself or by HPV is involved in anogenital carcinogenesis. We studied p53
overexpression by immunohistochemical methods, and HPV/DNA by non isotopic in
situ hybridization method in 137 anogenital lesions. Immunoreactivity for p53
was seen in 5% of condylomata acuminata, in 12% of low-grade CINs, in 3.5% of
high-grade CINs, and in 17% of invasive cervical carcinomas. Two (67%) of
three condylomata acuminate p53+ harboured HPV/DNA. The concomitant presence
of p53 and HPV was not detected in intraepithelial and invasive cervical
lesions. Our findings suggest that p53 inactivation does not seem to play an
important role in anogenital carcinogenesis. Further investigation of the
concomitant presence of p53 and HPV in condylomata acuminate and its role in
recurrences or progression of these lesions is needed.

<6>
AN 99086861
AU Melbye M. Frisch M.
IN Department of Epidemiology Research, Danish Epidemiology Science Centre,
Statens Serum Institut, Copenhagen, Denmark.
TI The role of human papillomaviruses in anogenital cancers.
[Review] [79 refs]
SO Seminars in Cancer Biology. 8(4):307-13, 1998 Aug.
LM Some issues available on Web. Check catalog for details.
AB There is substantial evidence to suggest that common risk factors exist for
cancer of the cervix and other anogenital cancers. Cervical cancer has been
etiologically linked with venereal types of human
papillomavirus (HPV) and the same types of HPV are being found in other
anogenital tissues. The question is to what extent these HPV types may also
contribute to carcinogenesis in anogenital cancer other than cervical cancer.
In this review some general aspects of the natural history of HPV are
presented followed by a description of the incidence and risk factors for
anal, vulvar, and penile cancer. Main focus is given to the evidence for an
association between these cancers and HPV. [References: 79]

<7>
AN 99052308
AU Frisch M. Glimelius B. van den Brule AJ. Wohlfahrt J. Meijer CJ.
Walboomers JM. Adami HO. Melbye M.
IN Department of Epidemiology Research, Danish Epidemiology Science Centre,
Statens Serum Institut, Copenhagen.
TI Benign anal lesions, inflammatory bowel disease and risk for high-risk
human papillomavirus-positive and -negative anal carcinoma.
SO British Journal of Cancer. 78(11):1534-8, 1998 Dec.
LM Dana Biomedical Library (Dana).
AB A central role in anal carcinogenesis of high-risk types of
human papillomaviruses (hrHPV) was recently established, but
the possible role of benign anal lesions has not been addressed in
hrHPV-positive and -negative anal cancers. As part of a population-based
case-control study in Denmark and Sweden, we interviewed 417 case patients
(93 men and 324 women) diagnosed during the period 1991-94 with invasive or
in situ anal cancer, 534 patients with adenocarcinoma of the rectum and 554
population controls. Anal cancer specimens (n = 388) were tested for HPV by
the polymerase chain reaction. Excluding the 5 years immediately before
diagnosis, men, but not women, with anal cancer reported a history of
haemorrhoids [multivariate odds ratio (OR) 1.8; 95% confidence interval (CI)
1.04-3.2] and unspecific anal irritation (OR 4.5; CI 2.3-8.7) significantly
more often than controls. Women with anal cancer did not report a history of
benign anal lesions other than anal abscess to any greater extent than
controls, but they had used anal suppositories more often (OR 1.5; CI
1.1-2.0). Patients with hrHPV in anal cancer tissue (84%) and those without
(16%) reported similar histories of most benign anal lesions, but anal
fissure or fistula was more common among hrHPV-positive cases. Ulcerative
colitis and Crohn's disease, reported by <1% of study participants, were not
associated with anal cancer risk. The higher proportion of hrHPV-positive
anal cancers among case patients with anal fissure or fistula suggests that
such mucosal lesions may provide direct viral access to basal epithelial
layers. Since risk associations with benign anal lesions in men may be
confounded by unreported sexual behaviour, and since risk associations in
women were generally negative, it seems unlikely that benign anal lesions act
as promoters in hrHPV-associated anal carcinogenesis. Moreover, benign anal
lesions appear not to be linked to an alternative, hrHPV-unassociated causal
pathway to anal cancer. Ulcerative colitis and Crohn's disease were not
supported as causal factors for anal cancer.

<8>
AN 98400219
AU Xi LF. Critchlow CW. Wheeler CM. Koutsky LA. Galloway DA. Kuypers J.
Hughes JP. Hawes SE. Surawicz C. Goldbaum G. Holmes KK. Kiviat NB.
IN Department of Epidemiology, School of Public Health and Community Medicine,
University of Washington, Seattle 98195, USA.
TI Risk of anal carcinoma in situ in relation to human
papillomavirus type 16 variants.
SO Cancer Research. 58(17):3839-44, 1998 Sep 1.
LM Pre-1993 at Dana,1993-date at MFHSL.
AB Infection with human papillomavirus (HPV), especially
HPV16, is central to the development of squamous anogenital cancers and their
precursor lesions, termed "squamous intraepithelial neoplasias." Men who have
sex with men, particularly those who are infected with HIV, are at a high
risk for anal infection with HPV16 and for low-grade anal neoplasia; however,
only a subset of these men develop anal invasive cancer or its immediate
precursor lesion, anal carcinoma in situ (CIS). To examine the hypothesis
that certain variants of HPV16 are most strongly associated with development
of anal CIS, we followed 589 men who have sex with men whose initial anal
cytological smears did not show anal CIS. Anoscopy, anal cytology, and
PCR-based assays for detection and classification of HPV types were performed
every 4-6 months, with HPV16 further classified by single-stranded
conformation polymorphism analysis as being a prototype-like (PL) or
non-prototype-like (NPL) variant. Anal CIS was histologically confirmed in 6
of 384 (1.6%) consistently HPV16-negative men, in 12 of 183 (6.6%) men with
HPV16 PL variants, and in 4 of 22 (18.2%) men with HPV16 NPL variants. After
adjustment for anal cytological diagnoses at study entry, HIV status and CD4
count, and detection of HPV types other than type 16, men with HPV16 NPL
variants were 3.2 times (95% confidence interval, 1.0-10.3) more likely to
develop anal CIS than were those with PL variants. Neither detection of HPV16
DNA at high levels nor detection of HPV16 DNA for a prolonged period, factors
that we previously demonstrated to be associated with risk of high-grade anal
squamous intraepithelial neoplasia, was significantly associated with HPV16
NPL variants. The biological mechanism relating to Ihis excess risk remains
undetermined.

<9>
AN 98302354
AU Poletti PA. Halfon A. Marti MC.
IN Policlinique de chirurgie, Hopital Cantonal Universitaire de Geneve,
Switzerland.
TI Papillomavirus and anal carcinoma.
SO International Journal of Colorectal Disease. 13(2):108-11, 1998.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.
AB Human papilloma virus (HPV; 16 and 18) is known to play an
important etiologic role in cervical dysplasia, but its relationship with
anal carcinoma is still unclear. Surgical samples from 80 female patients
treated for anal epidermoid carcinoma in the Polyclinic of Surgery in Geneva
between 1976 and 1989 were retrospectively studied. Of these, HPV detection
was performed in 41 whose DNA was preserved well enough to allow such an
analysis. Seventeen (42%) samples contained HPV, with a high percentage of
high risk HPV (15/41, 36%). Thirty-eight of the 80 patients had a cervical
smear, of which 18% revealed cervical carcinoma. When compared with
epidemiological data, the results of this study suggest that genital HPV
infection predisposes not only to cervical cancer, but also to anal
carcinoma, possibly by means of contiguous contamination.

<10>
AN 98374958
AU Palefsky JM.
IN Department of Laboratory Medicine and Stomatology, University of California,
San Francisco 94143, USA.
TI Human papillomavirus infection and anogenital neoplasia in
human immunodeficiency virus-positive men and women.
[Review] [34 refs]
SO Journal of the National Cancer Institute. Monographs. (23):15-20, 1998.
LM Pre-1993 at Dana,1993-date at MFHSL.
AB Human immunodeficiency virus (HIV)-positive women have a
higher prevalence of human papillomavirus (HPV) infection in
the cervix and anus, as well as squamous intraepithelial
lesions (SILs) at these sites, than do HIV-negative women matched for age and
HIV risk factors. Similarly, HIV-positive homosexual or bisexual men have a
higher prevalence of anal HPV infection and anal SIL than do HIV-negative
homosexual or bisexual men. In HIV-positive individuals, the prevalence of
HPV infection, the proportion infected with multiple HPV types, and the
prevalence of anogenital SILs increase with decreasing CD4 count. This
situation may reflect loss of systemic immune response to HPV antigens or
local HPV-HIV interactions at the tissue or cellular level. Despite the high
levels of anogenital SILs, to date, there has not been a significant increase
in reported cases of invasive anogenital cancer in HIV-positive individuals.
However, several years may be required for SIL to progress to invasive
cancer, and the advent of newer therapies for HIV that are expected to
prolong survival may paradoxically increase the risk of progression to cancer
in individuals with SILs if these lesions do not regress spontaneously and
remain untreated. [References: 34]

<11>
AN 98314530
AU Friedman HB. Saah AJ. Sherman ME. Busseniers AE. Blackwelder WC. Kaslow
RA. Ghaffari AM. Daniel RW. Shah KV.
IN Division of Microbiology and Infectious Diseases, National Institute of
Allergy and Infectious Diseases, National Institutes of Health, Rockville,
Maryland, USA. hfriedma@usuhs.mil
TI Human papillomavirus, anal squamous
intraepithelial lesions, and human immunodeficiency virus in
a cohort of gay men.
SO Journal of Infectious Diseases. 178(1):45-52, 1998 Jul.
LM Pre-1993 at Dana,1993-date at MFHSL.
AB Cross-sectional associations between human papillomavirus
(HPV), anal squamous intraepithelial lesions (SIL), and
human immunodeficiency virus (HIV) were studied in a cohort
of gay men. HPV DNA was detected by generic and type-specific polymerase
chain reaction (PCR) probes and hybrid capture assay (HC). HPV virus load was
estimated by HC relative light unit (RLU) ratio. HPV prevalence, number of
HPV types detected, and HC RLU ratios were each greater in HIV-positive than
HIV-negative participants. Further, among HIV-positive men, HC RLU ratio was
inversely associated with CD4 cell count. SIL was more frequent in
HIV-positive participants, particularly those with a CD4 cell count
<200/microL and was positively associated with HPV. Men with a high HC RLU
ratio were nearly 3 times more likely to have SIL than were those both PCR-
and HC-negative. These data support that HIV augments HPV-associated anal
disease in this population.

<12>
AN 98167829
AU Vernon SD. Unger ER. Reeves WC.
TI Human papillomaviruses and anogenital cancer [letter;
comment].
CM Comment on: N Engl J Med 1997 Nov 6;337(19):1343-9, Comment on: N Engl J Med
1997 Nov 6;337(19):1350-8, Comment on: N Engl J Med 1997 Nov 6;337(19):1386-8
SO New England Journal of Medicine. 338(13):921-2, 1998 Mar 26.
LM Dana(complete) &MFHSL(1990-date);also Web,check catalog .

<13>
AN 98000011
AU Shah KV.
TI Human papillomaviruses and anogenital cancers [editorial;
comment] [see comments].
CM Comment on: N Engl J Med 1997 Nov 6;337(19):1343-9, Comment on: N Engl J Med
1997 Nov 6;337(19):1350-8, Comment in: N Engl J Med 1998 Mar 26;338(13):921-2
SO New England Journal of Medicine. 337(19):1386-8, 1997 Nov 6.
LM Dana(complete) &MFHSL(1990-date);also Web,check catalog .

<14>
AN 97447093
AU Tilston P.
IN Department of Clinical Virology, Manchester Central Laboratory Services,
Manchester Royal Infirmary, UK.
TI Anal human papillomavirus and anal cancer. [Review] [108
refs]
SO Journal of Clinical Pathology. 50(8):625-34, 1997 Aug.
LM Pre-1993 Dana; 1993-dateMFHSL;for Web access-check catalog

<15>
AN 97413392
AU Sarmiento JM. Wolff BG. Burgart LJ. Frizelle FA. Ilstrup DM.
IN Division of Colon & Rectal Surgery, Mayo Clinic and Mayo Foundation,
Rochester, Minnesota 55905, USA.
TI Perianal Bowen's disease: associated tumors, human
papillomavirus, surgery, and other controversies.
SO Diseases of the Colon & Rectum. 40(8):912-8, 1997 Aug.
LM Pre-1993 Dana; 1993-date MFHSL (Incomplete, check catalog)
AB BACKGROUND: Perianal Bowen's disease (BD) is an intraepithelial
nonkeratinizing carcinoma, associated historically with internal tumors.
METHODS: A review of patients with perianal BD presenting consecutively
during a 25-year span was undertaken, excluding Bowenoid papulosis and
contiguous genital BD. Histologic slides were resubmitted for review by an
experienced pathologist, in a "blind" fashion among other slides. Follow-up
was updated in every patient. Survival and recurrence curves were generated
by the Kaplan-Meier method and were compared with a normal age-matched
population (log-rank test). RESULTS: Nineteen patients were identified; 15 of
them were females. Mean age +/- standard deviation was 49.6 +/- 10.6 years.
Five patients had a coincidental diagnosis (hemorrhoidectomy or wart
excision). No associated carcinomas were found; however, eight patients had
isolated BD of the vulva. Eleven patients had a history of anal warts,
cervical/vulvar dysplasia, or both. Wide resection, including V-Y flaps, was
performed in 18 patients without dysfunction. One-year and five-year
recurrence was 16 and 31 percent. Recurrence was treated in all but one case
by wider resection. Mean follow-up was 8.4 years. Five-year survival was 75
percent, lower than the matched population (P = 0.001); however, only one
death was related to BD. CONCLUSIONS: Perianal BD has no association with
internal tumors. Despite a high rate of recurrence, perianal BD can be
treated by local excision. An increased rate of human
papilloma virus-related entities was found, which could suggest a causative
role.

<16>
AN 97424496
AU Unger ER. Vernon SD. Lee DR. Miller DL. Sharma S. Clancy KA. Hart CE.
Reeves WC.
IN Department of Pathology and Laboratory Medicine, Emory University, Atlanta,
Ga., USA.
TI Human papillomavirus type in anal epithelial lesions is
influenced by human immunodeficiency virus.
SO Archives of Pathology & Laboratory Medicine. 121(8):820-4, 1997 Aug.
LM Pre-1993 at Dana,1993-date at MFHSL.
AB BACKGROUND AND OBJECTIVE: Infection with human
immunodeficiency virus (HIV) increases the risk for human
papillomavirus (HPV)-associated genital neoplasia. Human
immunodeficiency virus-infected patients also have higher rates of treatment
failure and more rapid neoplastic progression. Impaired immune function does
not entirely explain these clinical observations. This pilot project was
designed to investigate the hypothesis that HIV infection is associated with
changes in HPV type and integration within anogenital lesions that could
explain the increased risk of neoplastic progression. METHODS: Anal
neoplastic lesions from patients with and without HIV infection were analyzed
for the presence, type, and integration status of HPV by colorimetric in situ
hybridization. Tissue localization of HIV was evaluated by p24
immunohistochemistry and HIV-1 DNA polymerase chain reaction. Results for
matched histology were compared for the two patient groups. RESULTS: For all
lesions, the presence of high-risk HPV types and multiple HPV types was
strongly associated with HIV infection (P = .003 and .0003, respectively).
For lesions with matched histology there was no association of HPV
integration with HIV status. Tissue localization of HIV did not significantly
influence HPV type or integration. CONCLUSIONS: The presence of high-risk HPV
types and multiple types within low-grade lesions may explain the increased
risk of neoplastic progression in HIV patients. Colocalization of HIV and HPV
does not appear to be required for this effect. There is no evidence that HPV
integration is influenced by HIV infection.

<17>
AN 97291988
AU Majewski S. Jablonska S.
IN Department of Dermatology, Warsaw School of Medicine, Poland.
TI Human papillomavirus-associated tumors of the skin and
mucosa. [Review] [272 refs]
SO Journal of the American Academy of Dermatology. 36(5 Pt 1):659-85; quiz
686-8, 1997 May.
LM Pre-1993 Dana; 1993-date MFHSL (Incomplete, check catalog)
AB This review discusses diseases of the lower genital tract in which the
presence of human papillomavirus (HPV) DNA is well
documented. We discuss epidemiologic, clinical, and experimental data
supporting a causative role for HPV in mucosal malignancies, with emphasis on
the role of viral and host factors in their pathogenesis. Of special interest
is the recently discovered association of cutaneous tumors with HPVs,
previously known only for tumors in epidermodysplasia verruciformis (EV). The
frequent detection of EV-specific or EV-related HPVs in immunosuppressed
persons and in cutaneous tumors in the general population supports the
importance of EV as a model of cutaneous oncogenesis. We also discuss recent
serologic findings based on enzyme-linked immunosorbent assay results with
the use of viruslike particles. This is important both for detection of
present or past HPV infection and for epidemiologic and immunologic studies.
Novel therapeutic modalities for HPV tumors and prospects for prophylactic
and therapeutic vaccination are presented. [References: 272]

<18>
AN 97283383
AU Berner A. Franzen S. Holm R.
IN Department of Pathology, Norwegian Radium Hospital, Oslo, Norway.
TI HPV 16 infection in a patient with two primary squamous cell carcinomas: of
the uterine cervix and the anal mucosa.
SO APMIS. 105(3):207-12, 1997 Mar.
LM Dana. Incomplete holdings, check catalog.
AB A 43-year-old woman presented with metrorrhagia and a polypoid anal tumor.
Cervical dilatation and endocervical curettage and resection of the anal
tumor revealed two primary squamous cell carcinomas: of the uterine cervix
and the anal mucosa. HPV 16 was identified in both tumors using an in situ
hybridization technique with probes against HPV 6, 11, 16, 18, 31 and 33. The
cervical carcinoma was weakly positive for p53 protein, whereas the anal
tumor was p53 protein negative. Five years later a recurrence of the cervical
carcinoma was diagnosed and a hysterectomy was performed. Of 3,013 patients
with squamous cell carcinoma of either the cervix or the
anus registered in our files, only one had a primary
carcinoma in both locations. It was concluded hat HPV-16-induced squamous
cell carcinoma may occur simultaneously in the cervix and the
anus, and carcinoma in either of the two locations has to be
ruled out when dealing with HPV infection in the anogenital tract.

<19>
AN 97195658
AU Arends MJ. Benton EC. McLaren KM. Stark LA. Hunter JA. Bird CC.
IN Department of Pathology, Edinburgh University Medical School, UK.
TI Renal allograft recipients with high susceptibility to cutaneous malignancy
have an increased prevalence of human papillomavirus DNA in
skin tumours and a greater risk of anogenital malignancy.
SO British Journal of Cancer. 75(5):722-8, 1997.
LM Dana Biomedical Library (Dana).
AB Renal allograft recipients (RARs) have a well-documented increased incidence
of viral warts and cutaneous neoplasia, particularly those with long graft
life and high sun exposure. A clinicopathological survey of 69 RARs in
south-east Scotland, with follow-up periods of up to 28 years after
transplantation, revealed marked variation in patient susceptibility to
cutaneous malignancy with concomitant variation in HPV prevalence. Skin
cancers were found in 34 patients. Eight patients showed high susceptibility
[defined as more than four intraepidermal carcinomas (IECs) or invasive
squamous cell carcinomas (SCCs)] 42 had intermediate susceptibility (1-3 IECs
or SCCs, or >3 keratoses) and 18 had low susceptibility (< or = 3 keratoses
and no cancers). SCCs, IECs and keratoses from the high-susceptibility group
were found to have greater prevalences of human
papillomavirus (HPV) DNA (56%, 45% and 50% respectively), than SCCs (0%) and
IECs (33%) from intermediate-susceptibility RARs and keratoses (36%) from the
combined intermediate- and low-susceptibility groups and compared with a
group of immunocompetent controls (27%, 20% and 15% respectively). No
differences in p53 protein accumulation, determined immunohistochemically,
were observed in tumours from the three groups. Categorization of RARs by
susceptibility to cutaneous malignancy provides clinically useful
information, as significantly more high-susceptibility patients (38%)
developed aggressive, potentially lethal anogenital or cutaneous squamous
cell cancers than did patients in the intermediate group (5%, P=0.005) or the
low-susceptibility group (0%).

<20>
AN 97430249
AU Galloway DA. McDougall JK.
IN Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle,
WA 98109, USA.
TI The disruption of cell cycle checkpoints by papillomavirus oncoproteins
contributes to anogenital neoplasia. [Review] [49 refs]
SO Seminars in Cancer Biology. 7(6):309-15, 1996 Dec.
LM Some issues available on Web. Check catalog for details.
AB Human cancer are characterized by the failure of cell cycle
checkpoints resulting in genetic instability. Human
papillomaviruses contribute to the development of anogenital malignancies
because the E6 and R7 oncoproteins from high risk HPV types are able to
disrupt the integrity of these checkpoints. HPV 16 E7 prevents suprabasal
cells from exiting the cell cycle, thus increasing the pool of replicating
cells that are available for additional 'hits'. Cells that suffer DNA of
chromosome damage are not eliminated because E6 and E7 are able to bypass G1
and G2 damage-induced checkpoints. The activation, or inactivation, of
additional cellular genes required for invasion and metastasis may not be a
direct consequence of the E6/E7 oncoproteins. [References: 49]

<21>
AN 97167168
AU Williams GR. Lu QL. Love SB. Talbot IC. Northover JM.
IN ICRF Colorectal Unit, St. Mark's Hospital, Northwick Park, Watford Road,
Harrow, UK.
TI Properties of HPV-positive and HPV-negative anal carcinomas [see comments].
CM Comment in: J Pathol 1997 Sep;183(1):126
SO Journal of Pathology. 180(4):378-82, 1996 Dec.
LM Pre-1993 Dana; 1993-dateMFHSL;for Web access-check catalog
AB Evidence of human papillomavirus (HPV) can be found in up
to 85 per cent of anal carcinomas. In the vulva, a discrete subset of
HPV-positive carcinomas which show koilocytic morphology and distinct
clinical features has recently been identified (warty carcinoma). The
morphological and prognostic features of HPV-positive and HPV-negative anal
carcinomas were compared in this study of the tumour distribution of HPV DNA.
Vulval and anal neoplasia are similar in many ways and we have also looked to
see if their similarity extends to 'warty' morphology in relation to HPV
status. Thirty-five resection specimens of anal carcinoma were examined with
biotin-labelled probes for HPV 6, 11, 16, and 18 DNA, using a non-isotopic in
situ hybridization (ISH) technique. No tumour was found to contain HPV 6, 11,
or 18. Twenty-four (72 per cent) showed positivity for HPV 16 DNA. Staining
was homogeneous and independent of local squamous, basaloid, or ductal
differentiation. The majority of tumours showed staining suggestive of
episomal, non-productive HPV infection. HPV-positive tumours were more likely
to occur in the anal canal than perianally and to show a mixed squamous and
basaloid appearance. No difference between the two groups was found in
patient age, presence of adjacent dysplasia, ductal differentiation, or
prognosis. There was no correlation between condylomatous tumour morphology
and HPV 16 DNA positivity; thus, a subset equivalent to vulval warty
carcinoma could not be identified.

<22>
AN 96432366
AU Schon HJ. Grgurin M. Szekeres T. Schurz B.
IN Institute of Medical Chemistry, University of Vienna.
TI A new mode of treatment of human papilloma virus associated
anogenital lesions using a nonsteroid estrogen analogue.
SO Wiener Klinische Wochenschrift. 108(2):45-7, 1996.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.
AB Human papilloma virus (HPV)-induced condylomata acuminata
in both sexes, as well as cervical dysplasias were treated locally with an
ointment or a cream containing 25 mg clomiphene citrate per gram for a
fortnight. The DNA of HPV 6, 11, HPV 16, 18, and HPV 31, 35, 51 was monitored
pre- and post-therapeutically using an in situ hybridization assay. The
therapeutic response to the drug was demonstrated by the disappearance of
condylomata acuminata (100%), HPV DNA in cervical dysplasia (up to 80%), and
penile genital warts (75%). Under this therapeutic regimen 78% of all cases
treated became negative for the probed HPV. The pharmacological action of the
drug was diminished in HPV 16, 18 positive lesions. Clomiphene is shown to be
an effective anti-HPV drug.

<23>
AN 96375909
AU Vincent-Salomon A. de la Rochefordiere A. Salmon R. Validire P. Zafrani
B. Sastre-Garau X.
IN Department of Pathology, Institut Curie, Paris, France.
TI Frequent association of human papillomavirus 16 and 18 DNA
with anal squamous cell and basaloid carcinoma.
SO Modern Pathology. 9(6):614-20, 1996 Jun.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.
AB Human papillomaviruses (HPVs) play a major role in the
development of genital neoplasia. Their role in anal carcinogenesis is less
clear, and the rate of HPV genome detected in invasive anal carcinoma varies
considerably in the different reports. Moreover, the relationship of HPV to
basaloid carcinoma, claimed to represent a histologic type different from the
common squamous cell carcinoma, is still controversial. By use of both
polymerase chain reaction and Southern blot hybridization on DNA extracted
from frozen tissue specimens, we looked for HPV sequences in 12 cases of
squamous cell carcinoma, in 9 cases of basaloid invasive carcinoma, in 1 case
of carcinoma in situ, and in 1 case of Paget's disease of the anal canal. We
have looked for correlations between virologic data and histologic types of
tumors, and analyzed the clinical characteristics of HPV-positive and
HPV-negative lesions. In our series, 20 (74%) of 27 cases of invasive anal
carcinoma were positive for HPV DNA by Southern blot hybridization and/or
polymerase chain reaction. HPV 16 DNA was found in 17 cases, HPV 18 in 2
cases, and in 1 case, the type of the HPV sequences detected remained
undetermined (HPV X). Histovirologic correlations showed that 12 of 18
squamous cell carcinomas were associated with HPV 16 and that 8 of 9 cases of
basaloid carcinoma were HPV positive; 5 case corresponded to HPV 16, 2 cases
to HPV 18, and 1 case to HPV X. The carcinoma in situ case and the Paget's
disease case were negative. An analysis of these data within the framework of
the literature indicates that approximately 75% of cases of invasive anal
carcinoma can actually be considered associated with HPV sequences. Basaloid
carcinoma is also frequently associated with HPV genomes and is more likely
to represent a histologic variant of squamous cell carcinoma than a separate
entity. No clinical characteristics related to the HPV status of the tumors
were observed in our series. Epidemiologic data on cervical, anal, and vulvar
neoplasia are compared and their relation to the oncogenic properties of HPV
in these different tissues are discussed.

<24>
AN 96265770
AU Munoz-Jimenez F. Louredo-Mendez AM. Turegano-Fuentes F. del
Valle-Hernandez E. Lacruz-Pelea C.
IN Department of General Surgery, General University Hospital, Gregorio
Maranon, Madrid, Spain.
TI Squamous cell carcinomas of the anus and infection with
human papillomavirus in patients with AIDS.
SO European Journal of Surgery. 162(3):251-3, 1996 Mar.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.

<25>
AN 96181331
AU Ramanujam PS. Venkatesh KS. Co Barnett T. Fietz MJ.
IN Department of Oncology and Pathology, Walter O. Boswell Memorial Hospital,
Sun City, Arizona 85351, USA.
TI Study of human papillomavirus infection in patients with
anal squamous carcinoma.
SO Diseases of the Colon & Rectum. 39(1):37-9, 1996 Jan.
LM Pre-1993 Dana; 1993-date MFHSL (Incomplete, check catalog)
AB PURPOSE: The purpose of this study was to determine the incidence of
human papillomavirus deoxyribonucleic acid (HPV DNA) in anal
squamous carcinoma. METHODS: HPV DNA in situ hybridization for HPV Types 6,
11, 16, 18, 31, 33, and 35 was performed on the formalin-fixed,
paraffin-embedded tissue from 53 perianal and anal squamous carcinomas and 10
controls. RESULTS: HPV DNA sequences were identified in 18 of 53 anal
squamous carcinomas (34 percent). All 10 controls were negative for HPV DNA.
Of the 18 positive patients, 10 were perianal squamous carcinomas, and 8 were
anal canal squamous carcinomas. Six of the perianal carcinomas were positive
for HPV Types 6 and 11. The remaining four perianal carcinomas and all eight
of the anal canal carcinomas were positive for HPV Types 16 and 18.
CONCLUSION: HPV DNA sequences can be identified in anal squamous carcinomas.
Anal squamous epithelium is another site where HPV infection may carry a risk
for malignant transformation. One-third of anal squamous carcinomas may be
associated with prior HPV infection. Patients with anogenital HPV infection
should be routinely screened for anal squamous lesions.

<26>
AN 96126180
AU Critchlow CW. Surawicz CM. Holmes KK. Kuypers J. Daling JR. Hawes SE.
Goldbaum GM. Sayer J. Hurt C. Dunphy C. et al.
IN Department of Epidemiology, School of Public Health and Community Medicine,
University of Washington, Seattle 98195, USA.
TI Prospective study of high grade anal squamous intraepithelial neoplasia in a
cohort of homosexual men: influence of HIV infection, immunosuppression and
human papillomavirus infection.
SO AIDS. 9(11):1255-62, 1995 Nov.
LM Pre-1993 Dana; 1993-date MFHSL (Incomplete, check catalog)
AB OBJECTIVE: To determine the risk of developing high grade anal squamous
intraepithelial neoplasia (HG-AIN) in relation to HIV infection and
immunosuppression, after controlling for the effects of
human papillomavirus (HPV) infection. DESIGN: Prospective
cohort study of 158 HIV-seropositive and 147 HIV-seronegative homosexual men
presenting to a community-based clinic with initially negative anal cytologic
and colposcopic findings. METHODS: Subjects completed self-administered
questionnaires, underwent cytologic screening, and standardized unaided and
colposcopic examination of the proximal anal canal for presence of
abnormalities suggestive of AIN. Anal specimens were screened for HPV DNA.
RESULTS: HG-AIN developed in eight (5.4%) and 24 (15.2%) HIV-seronegative and
-seropositive men, respectively. Risk of HG-AIN among HIV-seronegative men
was associated with detection of anal HPV types 16 or 18 by Southern transfer
hybridization (STH), detection of HPV 16 or 18 at the lower levels by
polymerase chain reaction but not by STH, and with number of positive HPV
tests; HG-AIN risk among HIV-seropositive men was associated with detection
of HPV 16 or 18 only by STH, detection of HPV types other than 16 or 18, CD4
count < or = 500 x 10(6)/l, and number of positive HPV tests. HIV-induced
immunosuppression remained an independent predictor of HG-AIN after adjusting
for type and level of detection of HPV; HIV infection predicted HG-AIN risk
after adjustment for number of positive HPV tests. CONCLUSIONS: The
association of HG-AIN with HIV, independent of HPV type, level of HPV
detection and number of positive HPV tests, suggests that this increased risk
cannot be entirely explained by an effect of HIV on HPV detection. Future
studies focusing on factors more specific to the local microenvironment in
the anal canal should help clarify these issues.

<27>
AN 95407598
AU Shroyer KR. Brookes CG. Markham NE. Shroyer AL.
IN Department of Pathology, University of Colorado Health Sciences Center,
Denver, USA.
TI Detection of human papillomavirus in anorectal squamous
cell carcinoma. Correlation with basaloid pattern of differentiation.
SO American Journal of Clinical Pathology. 104(3):299-305, 1995 Sep.
LM Pre-1993 at Dana,1993-date at MFHSL.
AB Polymerase chain reaction (PCR) and in situ hybridization were used to test
for the presence of human papillomavirus (HPV) DNA in cases
of anorectal squamous cell carcinoma. Human papillomavirus
was detected by PCR with L1 consensus sequence primers in 22 of 27 cases,
including 10 of 11 cases with a prominent basaloid pattern and 12 of 16 cases
without basaloid patterns of differentiation. Slot blot hybridization
identified HPV type 16 as the most common type, present in 7 of 10 cases of
basaloid carcinoma and 10 of 12 cases without basaloid features. In situ
hybridization confirmed the presence of HPV in tumor cell nuclei of five
cases of basaloid carcinoma and in eight cases of squamous cell carcinoma
without basaloid pattern. The authors conclude that the prevalence of HPV in
cases of anorectal squamous cell carcinoma is unrelated to the presence or
absence of a basaloid pattern of differentiation.

<28>
AN 95406196
AU Noffsinger AE. Suzuk L. Hui YZ. Gal AA. Fenoglio-Preiser CM.
IN Department of Pathology and Laboratory Medicine, University of Cincinnati
College of Medicine, Ohio, USA.
TI Differential sensitivities of E6 type-specific and L1 consensus primers in
the detection of human papillomavirus in anal carcinoma.
SO Modern Pathology. 8(5):509-14, 1995 Jun.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.
AB Anogenital malignancy has been increasing in incidence in recent decades.
There is strong evidence in the literature suggesting that
human papillomavirus (HPV) plays a role in the genesis of
anogenital neoplasia. In addition, identification of oncogenic HPV types in
anogenital carcinomas may have prognostic significance. The method used to
detect HPV infection, however, affects the frequency with which viral DNA is
identified. We examined tissues from 56 patients with anal squamous cell
carcinoma for the presence of HPV DNA by in situ hybridization and polymerase
chain reaction using both consensus and type-specific primers to determine if
HPV detection varies when different methods are used. In situ hybridization
identified the presence of HPV DNA in 41.1% of patients. Polymerase chain
reaction using type-specific probes for the HPV E6 gene demonstrated HPV DNA
in 46% of anal carcinomas, whereas polymerase chain reaction with consensus
primers detected HPV DNA in only 16.3% of cases. All cases containing HPV
type 6 were identified with L1 primers, whereas only three of 23 cases
containing HPV type 16 were identified. The differences in the rate of HPV
detection by the two polymerase chain reactions methods are most likely
related to L1 gene loss in cells containing integrated HPV type 16.

<29>
AN 95356213
AU Birley HD. Hart CA. Stacey SN.
TI Human papillomaviruses and the genital tract: old virus,
new developments [editorial]. [Review] [22 refs]
SO Journal of Medical Microbiology. 43(2):81-4, 1995 Aug.
LM Dana Biomedical Library (Dana).

<30>
AN 95340910
AU Cooper K.
TI p53 in human papillomavirus associated anogenital cancers
[letter; comment].
CM Comment on: J Clin Pathol 1993 Jun;46(6):507-12
SO Journal of Clinical Pathology. 48(4):393, 1995 Apr.
LM Pre-1993 Dana; 1993-dateMFHSL;for Web access-check catalog

<31>
AN 95165467
AU Heino P. Eklund C. Fredriksson-Shanazarian V. Goldman S. Schiller JT.
Dillner J.
IN Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm,
Sweden.
TI Association of serum immunoglobulin G antibodies against
human papillomavirus type 16 capsids with anal epidermoid
carcinoma [see comments].
CM Comment in: J Natl Cancer Inst 1995 Mar 15;87(6):401-2
SO Journal of the National Cancer Institute. 87(6):437-40, 1995 Mar 15.
LM Pre-1993 Dana; 1993-dateMFHSL;for Web access-check catalog
AB BACKGROUND: Anal epidermoid carcinoma is a relatively rare tumor, but its
incidence has been increasing rapidly during the past few years. Genetic
material from the major oncogenic types of human
papillomavirus (HPV), types 16 and 18, has regularly been demonstrated in a
substantial proportion of anal cancers, suggesting an etiologic role of HPV
infection. Recently, serum antibodies against HPV type 16 capsids were shown
to be a serologic measure of HPV16 infection. PURPOSE: We investigated
whether serum antibodies against HPV16 capsids are associated with an
increased risk of developing anal cancer. METHODS: Serum samples from 64
patients (48 women and 16 men) with untreated anal epidermoid cancer and from
79 age- and sex-matched healthy blood donors were analyzed for the levels of
serum immunoglobulin G (IgG) against capsids of HPV16 by the enzyme-linked
immunosorbent assay. The levels of serum IgG against HPV type 6 and bovine
papillomavirus (BPV) capsids, as well as against HPV16 peptide antigens, were
also measured. RESULTS: Whereas antibodies against HPV6 or BPV capsids were
not significantly associated with anal cancer, the presence of IgG against
HPV16 capsids exceeding the anti-BPV antibody levels was demonstrated among
55% (35 of 64) of the case patients but only among 4% (three of 79) of the
control subjects (odds ratio [OR] = 30.4; 95% confidence interval [CI] =
8.4-161.5). Antibodies against HPV16 E2 and E7 peptides were also more common
among case patients (OR = 12.8 and 95% CI = 5.4-31.5 for E2; OR = 3.0 and 95%
CI = 1.4-6.7 for E7). CONCLUSION: The results suggest that HPV16 capsid
antibodies are serologic markers for anal cancer. IMPLICATION: Exposure to
HPV16 or related viruses appears to be a major risk factor in the majority of
anal cancers.

<32>
AN 95144675
AU Noffsinger AE. Hui YZ. Suzuk L. Yochman LK. Miller MA. Hurtubise P.
Gal AA. Fenoglio-Preiser CM.
IN Department of Pathology and Laboratory Medicine, University of Cincinnati
College of Medicine, OH 45267-0529.
TI The relationship of human papillomavirus to proliferation
and ploidy in carcinoma of the anus.
SO Cancer. 75(4):958-67, 1995 Feb 15.
LM Pre-1993 Dana; 1993-dateMFHSL;for Web access-check catalog
AB BACKGROUND. Human papillomavirus (HPV) infections have been
implicated in anogenital neoplasia in both sexes. In this study, the authors
postulated that HPV infections induce squamous epithelium to become
hyperproliferative and aneuploid. METHODS. To test this hypothesis, formalin
fixed, paraffin embedded tissues were analyzed for the presence of HPV by in
situ hybridization. S-phase fraction and DNA content were evaluated by flow
cytometry. Proliferative indices also were analyzed using an antibody to
proliferating cell nuclear antigen (PCNA). RESULTS. Human
papillomavirus DNA was present in 48.1% of the carcinomas. All but one
HPV-positive tumor contained HPV 16/18 DNA. The remaining tumor contained
only HPV 6/11. No correlation was found between HPV status, patient age, or
tumor differentiation. Thirty-three percent of tumors were aneuploid. Only
two patients had aneuploid tumors that were HPV-negative; these patients
received preoperative radiotherapy. The average S-phase fraction was
significantly higher (P < 0.01) in HPV-positive versus HPV-negative lesions.
The PCNA index for HPV positive tumors was also significantly higher than
that observed in negative tumors (p < 0.003). CONCLUSION. The presence of HPV
in tumor cells is significantly associated with an increased proliferative
rate and aneuploid status of tumors compared with HPV-negative tumors. These
findings are consistent with the fact that viral proteins binding to tumor
suppressor gene proteins can deregulate the cell cycle and lead to genomic
instability.

<33>
AN 94304548
AU Palefsky JM.
TI Anal human papillomavirus infection and anal cancer in
HIV-positive individuals: an emerging problem [editorial]. [Review] [93 refs]
SO AIDS. 8(3):283-95, 1994 Mar.
LM Pre-1993 Dana; 1993-date MFHSL (Incomplete, check catalog)

<34>
AN 94275455
AU Labropoulou V. Balamotis A. Tosca A. Rotola A. Mavromara-Nazos P.
IN Department of Virology, Hellenic Pasteur Institute, Athens, Greece.
TI Typing of human papillomaviruses in condylomata acuminata
from Greece.
SO Journal of Medical Virology. 42(3):259-63, 1994 Mar.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.
AB DNA samples from recurrent condylomata acuminata biopsies of Greek males and
females were examined for the presence of human
papillomavirus (HPV) DNA using high-stringency Southern blot hybridization
analysis. Of the twenty-six biopsies, 25 were positive for the HPV
6/11-related DNA sequences, and when further analyzed with the polymerase
chain reaction (PCR) the HPV-negative biopsy was also positive for HPV 6/11
DNA. Nineteen specimens were further characterized based on their Pstl
restriction endonuclease hybridization pattern. Twelve biopsies were positive
for HPV 6a, one biopsy was positive for HPV 11a, and one biopsy was positive
for HPV 6c DNA. Three specimens contained HPV 6/11 related DNA that gave an
unusual Pstl pattern, and one specimen appeared to represent a multiple HPV
infection containing HPV 6/11- and HPV 31/35/39-related sequences. Finally,
one sample contained a mixture of HPV 6a DNA and an HPV 6a-like genome.
Biopsies were also taken from adjacent apparently normal tissue, 0.5 cm away
from the lesion, in 19 of the patients. Only one of these was found to be
positive for HPV 6a DNA by Southern blot analysis.

<35>
AN 94228247
AU Ogunbiyi OA. Scholefield JH. Raftery AT. Smith JH. Duffy S. Sharp F.
Rogers K.
IN University Department of Surgery, Northern General Hospital, Sheffield, UK.
TI Prevalence of anal human papillomavirus infection and
intraepithelial neoplasia in renal allograft recipients.
SO British Journal of Surgery. 81(3):365-7, 1994 Mar.
LM Pre-1993 Dana; 1993-dateMFHSL;for Web access-check catalog
AB A study was performed to test the hypothesis that renal allograft recipients
are at high risk of developing anal human papillomavirus
(HPV) infection and anal intraepithelial neoplasia (AIN). A total of 133
renal allograft recipients and 145 control patients underwent anoscopy and
biopsy. A polymerase chain reaction was used to detect HPV16 DNA in biopsy
samples. A histological diagnosis of anal HPV infection or AIN was made in 32
allograft recipients (HPV infection, five; AIN I, 20; AIN II, three; AIN III,
three; AIN III and anal cancer, one). One subject with AIN was detected in
the control group. HPV16 DNA was detected in 47 and 12.4 per cent of anal
biopsies in the allograft and control groups respectively. Renal allograft
recipients are at high risk of developing anal HPV infection and neoplasia (P
< 0.05). Further studies are required to determine whether screening anal
examination is required in organ allograft recipients.

<36>
AN 94230649
AU Baccard-Longere M. Alpha-Bazin B. Chypre C. Sauvaigo S. Teoule R.
Bernard P. Seigneurin JM.
IN Service de Virologie, C.H.U. de Grenoble, France.
TI Fast solid support detection of human papillomavirus in in
vitro amplified DNA using a DNP-anti DNP monoclonal antibody couple.
SO Journal of Virological Methods. 46(1):29-38, 1994 Jan.
LM Dana Biomedical Library (Dana).
AB In some anogenital lesions the detection of certain types of
human papilloma virus, especially oncogenic types, is of
interest. In a first step during a prospective study, we compared two methods
for the detection of human papillomavirus (HPV) DNA in
clinical samples: Southern blotting followed by hybridization with a cloned
radioactive genomic probe and a classical polymerase chain reaction (PCR)
followed by hybridization with a 32P-labelled oligonucleotide probe. 118
biopsies and swabs were examined for HPV 6/11, 16, 18 and 33, 67 positive
reactions were found by both methods, 5 positives only by PCR and 2 positives
only by Southern blot for unidentified HPV. Patients with anogenital
condylomas, dysplasias and carcinomas or asymptomatic patients were studied.
Most high grade (II and III) dysplasias were associated with HPV 16 and HPV
18. Condylomata lesions and low grade dysplasia (grade I) were associated
mostly with HPV 6/11, mixed type of HPV, less frequently with HPV 16 or HPV
18. As a second step a nested PCR coupled to solid support detection method
was used as described by Sauvaigo et al. (1990) Nucleic Acids Res. 18,
3175-3183) to study a panel of 30 previously qualified different HPV DNA
extracts. In this procedure the second round of PCR amplification involves
biotinylated and dinitrophenylated labelled primers allowing the capture of
PCR amplified HPV DNA sequences on streptavidin coated tubes and its
revelation. We describe an improvement of HPV DNA detection by means of
single-step immunoenzymatic revelation involving anti-DNP monoclonal
antibodies conjugated to horseradish peroxidase enzyme. A perfect correlation
with the previous results was obtained. This solid support method allows a
faster and easier HPV typing compared to methods using membrane transfer.

<37>
AN 94168920
AU Northfelt DW.
IN AIDS/Oncology Clinic, University of California, San Francisco.
TI Cervical and anal neoplasia and HPV infection in persons with HIV infection.
[Review] [42 refs]
SO Oncology. 8(1):33-7; discussion 38-40, 1994 Jan.
LM Not at Dartmouth/DHMC libraries;request on interlibrary loan
AB Prolonged, severe immunodeficiency provides the necessary milieu for the
emergence of anogenital neoplasia caused by human
papillomaviruses. Cervical and anal neoplasia are likely to become more
common manifestations of HIV disease as patients with profound
immunodeficiency, who would have succumbed to opportunistic infections
earlier in the epidemic, are now surviving for extended periods of time
because of increasingly effective antiretroviral, prophylactic, and
antimicrobial therapies. Cervical cancer in the setting of HIV infection
appears to be a more aggressive disease, less likely to be successfully
treated by standard therapies, and consequently associated with a poorer
prognosis than in comparable non-HIV-infected women. Anecdotal observations
suggest that anal cancer in HIV-infected persons may share these features.
Strategies need to be developed for earlier detection and treatment of
neoplasia and anogenital cancer in the setting of HIV-induced
immunodeficiency. [References: 42]

<38>
AN 94119500
AU Ogunbiyi OA. Scholefield JH. Robertson G. Smith JH. Sharp F. Rogers K.
IN Department of Surgery, Northern General Hospital, Sheffield, United Kingdom.
TI Anal human papillomavirus infection and squamous neoplasia
in patients with invasive vulvar cancer.
SO Obstetrics & Gynecology. 83(2):212-6, 1994 Feb.
LM Pre-1993 at Dana,1993-date at MFHSL.
AB OBJECTIVE: To test the hypothesis that women with invasive vulvar cancer are
at high risk of developing human papillomavirus
(HPV)-associated anal squamous neoplasia. METHODS: Forty women (median age
54.5 years; range 25-86) who were being treated or had been treated for
invasive vulvar cancer and who had not had radiotherapy to the pelvis or
anogenital region underwent anal microendoscopy and biopsy. A second group of
80 women who were similar in age to the study group and had no history of
anogenital HPV infection or neoplasia formed the control group. The
polymerase chain reaction was used to detect HPV 16 DNA in the vulvar and
anal tissue samples from 33 patients in the study group and in the anal
biopsies of all controls. RESULTS: A histologic diagnosis of anal HPV
infection or squamous neoplasia was made in 19 of 40 biopsies (47.5%) in the
study group. These diagnoses consisted of one HPV, two anal squamous
intraepithelial lesions (SIL) grade I, 15 and SIL grade III (four of which
were associated with invasive anal cancers), and one invasive cancer in the
absence of anal SIL. Human papillomavirus 16 DNA was
detected in 16 of 33 (48.5%) of anal and 25 of 33 (75%) of vulvar biopsies.
In addition, HPV 16 was detected in both the anal and vulvar samples in 13 of
16 cases (81%) of anal SIL III and invasive anal squamous cancer. No evidence
of anal SIL was found in the controls, and HPV 16 DNA was identified in only
11 (13.7%) of the anal biopsies in this group. CONCLUSIONS: This study
provides further evidence for the etiologic relation between genital and anal
squamous neoplasia. Furthermore, it shows that women with vulvar cancer are
at high risk of having or developing HPV-associated anal neoplasia,
particularly in younger patients (P = .0006; 95% confidence interval 12-34).
Routine anal examination should be performed in patients with invasive vulvar
cancer.

<39>
AN 94087678
AU Ikenberg H. Goppinger A. Hilgarth M. Pfisterer J. Muller U. Hillemanns
HG. Pfleiderer A.
IN Department of Obstetrics and Gynecology, University of Freiburg, Germany.
TI Human papillomavirus, type 16, DNA in
multicentric anogenital neoplasia associated with idiopathic panmyelopathy. A
case report.
SO Journal of Reproductive Medicine. 38(10):820-2, 1993 Oct.
LM Pre-1993 Dana; 1993-date MFHSL (Incomplete, check catalog)
AB A 27-year-old woman suffering from panmyelopathy for six years presented
with a cervical low grade squamous intraepithelial lesion (SIL), vulvar high
grade SIL and perianal squamous cell carcinoma with an inguinal metastasis.
Southern blot hybridization with 32P-labeled human
papillomavirus (HPV) DNA revealed HPV 16 DNA in varying copy numbers in
material from the four locations. HPV 16 genomes persisting after surgery on
the perianal tumor area were no longer detectable after betatron
radiotherapy.

<40>
AN 94063842
AU Walts AE. Koeffler HP. Said JW.
IN Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical
Center, Los Angeles, CA 90048.
TI Localization of p53 protein and human papillomavirus in
anogenital squamous lesions: immunohistochemical and in situ hybridization
studies in benign, dysplastic, and malignant epithelia.
SO Human Pathology. 24(11):1238-42, 1993 Nov.
LM Pre-1993 at Dana,1993-date at MFHSL.
AB p53 Protein is a 53-kd nuclear phosphoprotein believed to play an important
role in controlling proliferation of neoplastic and normal cells. This
"natural tumor suppressor" can be rendered ineffective (or oncogenic) by
mutations in the p53 gene or by interactions with proteins synthesized by
DNA-transforming viruses, including specific subtypes of
human papillomavirus (HPV). We describe the localization of
p53 protein in association with HPV in paraffin sections of a spectrum of
benign, dysplastic, and malignant anogenital squamous epithelia using
immunohistochemical and in situ hybridization techniques. p53 Was detected in
81% of the 48 cases studied. Immunoreactivity for p53 was seen in 83% of the
benign and low-grade squamous intraepithelial lesions (SILs), in 73% of the
high-grade SILs, and in 86% of the infiltrating squamous carcinomas. In
high-grade SILs p53 staining was frequently observed in individual nuclei at
various levels of the abnormal epithelium and in the basal layer of the
adjacent epithelium, while in squamous metaplasia and low-grade SILs
immunostaining for p53 was limited to the basal layer of the epithelium. p53
Was detected in a slightly higher percentage of HPV-positive than
HPV-negative epithelia as determined by in situ hybridization. No correlation
was observed between p53 immunoreactivity and HPV subtypes. p53 Protein and
HPV were detected in anal lesions from a small group of
human immunodeficiency virus-positive individuals.
Antibodies currently available mainly demonstrate mutant forms of p53 protein
that are associated with longer half-lives than the wild-type protein, but
demonstration of p53 protein overexpression is not necessarily indicative of
malignancy.

<41>
AN 94142529
AU de Mello WA. de Barros VL. Ribeiro MR. Rahal P. Villa LL. Macedo JE.
Linhares AC.
IN Secao de Virus do Instituto Evandro Chagas, Fundacao Nacional de Saude,
Belem, PA, Brasil.
TI Human papillomavirus and anogenital cancers in northern
Brazil.
SO Memorias do Instituto Oswaldo Cruz. 87(3):445-7, 1992 Jul-Sep.
LM Dana. Incomplete holdings, check catalog.

<42>
AN 94073363
AU von Knebel Doeberitz M.
IN Institut fur Angewandte Tumorvirologie, Deutsches Krebsforschungszentrum,
Heidelberg, Germany.
TI Papillomaviruses in human disease: Part II. Molecular
biology and immunology of papillomavirus infections and carcinogenesis [see
comments]. [Review] [69 refs]
CM Comment in: Eur J Med 1993 Apr;2(4):254-5
SO European Journal of Medicine. 1(8):485-91, 1992 Dec.
LM Not at Dartmouth/DHMClibraries;request on interlibrary loan.
AB As summarized in the last issue of the EJM, human
papillomaviruses induce a great variety of neoplastic lesions of mucosal
epithelia and the skin. Particular types of these viruses are associated with
specific human cancers, most notably anogenital carcinomas.
These tumours account for about fifteen percent of the whole worldwide cancer
burden. However, recent epidemiological studies revealed that papillomavirus
infections including those with the cancer-related papillomavirus types are
very widespread even among asymptomatic healthy individuals. Here, the
current understanding of the molecular events leading to
papillomavirus-induced tumours will be reviewed. It is assumed that these
tumours arise as a consequence of several molecular modifications of
persistently papillomavirus-infected epithelial cells. Experimental studies
revealed that the virus types associated with anogenital cancers harbour two
potential oncogenes referred to as E6 and E7. These viral genes are
consistently expressed in HPV-associated anogenital carcinoma cells.
HPV-associated cervical carcinoma cells loose their neoplastic growth
properties if the expression of the E6 and E7 genes is inhibited. The
proteins encoded by these viral genes thus appear to be ideal targets for a
specific pharmacological approach to treat papillomavirus associated cancers
or their respective precursor lesions. Recent studies in animals furthermore
suggest that active vaccination with the viral oncoprotein E7 prevents growth
of papillomavirus associated tumours. Hence, the possibility arises that also
in man, vaccination with the viral transforming proteins might prevent the
development of papillomavirus associated cancers. [References: 69]