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o Updated 2014 Mar 17 06:53:00 AM: addition of bevacizumab to chemotherapy may

improve overall survival in patients with advanced cervical cancer (N Engl J Med 201 !eb 20" viewupdate#how more updates

Related Summaries:

o $uman papillomavirus %N& testing

o 'ervical cancer screeningo Management of cervical intraepithelial neoplasia ('N" and adenocarcinoma in situ ("o Management of abnormal cervical cytology

o $uman papillomavirus vaccine

)eneral nformation

Description:

o invasive carcinoma originating in transformation zone of cervi*+ most commonly in s,uamous

cells(-+"

o second most common cancer in women worldwide+ third most common cause of female cancermortality(1+2+-"

Tpes:

o histologic types

s,uamous cell carcinoma is most fre,uent type accounting for two.thirds of cervicalcancers(1+2+-+"

adenocarcinoma accounts for about 10/.20/ cervical cancers(1"

o small cell carcinoma rare compared to s!uamous cell carcinoma or

cer"ical adenocarcinoma based on retrospective cohort study evaluating incidence of small cell+

s,uamous cell+ and adenocarcinoma of cervi* 1 to 200- from #urveillance+Epidemiology+ and End esults (#EE" database

mean annual incidence of cervical cancer per 100+000 women

small cell carcinoma 0304

adenocarcinoma 132

s,uamous cell carcinoma 434

eference . 5bstet )ynecol 2006 Jun7111(4"81-

o other rare histologic types

clear cell carcinoma(-"

neuroendocrine carcinoma(-"

glassy cell carcinoma ()ynecol 5ncol 201 !eb early online"

#$o is most a%ected:

o women aged -0.9 years(9"

o 60/ of new cases occur in resource.poor countries(1+-"

o ma:ority of cases are in women who have never had a ;ap smear or participated regularly incytology screening program(9"

o women with $< infection("

o women living in rural =nited #tates have higher incidence of cervical cancer based on nationaldata 16 to 2001 with -+4 cases of cervical cancer (5bstet )ynecol 200 #ep7110(-"8461"

&ncidence'(re"alence:

o in developed countries(1+2"

decreasing incidence of s,uamous cell carcinoma due to screening capacity andavailability of human papilloma virus vaccine

increasing incidence of adenocarcinoma

o estimated )lo*al cer"ical cancer incidence 454+000 cases in 2010

based on population.based cancer registries+ vital registration data+ and verbalautopsy data from 16 countries from 160 to 2010

cervical cancer incidence annual rate increased -31/ from -6+000 cases in 160

200+000 cervical cancer.related deaths in 2010 including 4+000 women aged 19.years living in developing countries
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596538


2/55

eference . >ancet 2011 5ct 227-6(601"8141+ editorial can be found in>ancet 20115ct 227-6(601"812

o 4,3 per 100+000 annual incidence o- cer"ical cancer in .omen / 40 ears old in

United States

based on two population.based cancer registries

mean -+04- cases of invasive cervical carcinoma noted annually in women ? 0 years

old from 1 to 2006

annual incidenceo 3- per 100+000 women ? 0 years old

o 13 per 100+000 women aged 20.2 yearso 0319 per 100+000 women aged 19.1 years

eference . 5bstet )ynecol 2012 Nov7120(9"8111o ,1 per 100+000 .omen a)eadusted incidence o- cancer o- cer"i uteri in United

States

based on annual report of cancer status in =nited #tates with data for 200- to 200

incidence varied with ethnicity from 3 per 100+000 &sian@;aciAc slander women to1239 per 100+000 $ispanic women

age.ad:usted death rates for cancer of cervi* uteri 23 per 100+000 women+ varied withethnicity from 231 per 100+000 &sian@;aciAc slander women to 3 per 100+000 blacBwomen

eference .J Natl 'ancer nst 2011 May 710-("81 Shost 8ull Tetfull.

te*to 257,2 per 100+000 personears incidence o- in"asi"e cer"ical carcinoma in .omen

.it$out prior (ap screenin)

based on retrospective cohort study

9+-0 women with cytologic atypical s,uamous cells of undetermined signiAcance('.=#" from national cervical cancer screening database in Caiwan

overall incidence rate 1939 cases invasive cervical cancer per 100+000 person.years

23- cases invasive cervical cancer per 100+000 person.years in screened persons vs32932 cases in unscreened groups (hazard ratio 236+ p ? 03001"

eference . 5bstet )ynecol 200 &pr711-("8666

o 3641 per 100+000 .omenears cumulati"e incidence o- cer"ical cancer a-ter 3consecuti"e ne)ati"e smear tests

based on prospective cohort study

216+6 women aged 9.9 years and 9+-62 women aged -0. years at time ofthird consecutive negative smear test were followed up to 10 years

cumulative incidence rate of cervical cancer 1 in younger women vs3 -4 in olderwomen per 100+000 woman.years (not signiAcant"

cumulative incidence rate of cervical intraepithelial neoplasia grade D 1 twice as highin younger women vs3 older women (p ? 03001"

eference . MJ 200 &pr 27--68b1-9 Shost 8ull Tetfull.te*t+editorial

can be found inMJ 200 &pr 27--68b60 Shost 8ull Teto 639 per 100+000 females rate of invasive cervical cancer in 2002 (declined from 1032 in 16"

in =nited #tates (5bstet )ynecol 200 !eb710(2 ;t 1"8-40"+ correction can be found in 5bstet)ynecol 200 &pr710("81002

'auses8

o persistent infection with oncogenic types of human papillomavirus ($;


3/55

-1+ --+ -+ 4+ -+ 9+ -+ and 92 (M' nfect %is 201- &ug 1-71-(1"8-- Shost 8ullTetfull.te*t"

151 di%erent 9( tpes s$ould *e considered $i)$ris; tpeso based on pooled analysis of case.control studies

o pooled analysis of 11 case.control studies with 1+16 women with s,uamous

cell cervical cancer and 1+26 control womeno high.risB types included 14+ 16+ -1+ --+ -9+ -+ 9+ 91+ 92+ 94+ 96+ 9+ 46+ -+

62+ and probably 24+ 9-+ and 44o low.risB types included 4+ 11+ 0+ 2+ -+ + 9+ 41+ 0+ 2+ 61+ and ';4106

o eference . N Engl J Med 200- !eb 47-6(4"8916+editorial can be found inNEngl J Med 200- !eb 47-6(4"86+commentary can be found in N Engl J Med 200- May197-6(20"8200+ N Engl J Med 200- &ug 7-(4"841

o 9(16 associated .it$ cer"ical cancer

based on analysis of - patients with adenocarcinoma of cervi* and 1-2 patients withs,uamous cell carcinoma of cervi* in taly

$;< infection in 2/ with adenocarcinoma and 69/ in s,uamous cell carcinoma

$; and cer"ical cancer


911 women with 'N - or cervical cancer at 1 center had test for $;< %N&

after e*clusion of inade,uate samples and@or further histologic review+ $;< %N&associated with all conArmed 'N - and cervical cancero among 1 with 'N -+ were $;


4/55

o nodal spread common+ usually occurs in stepwise manner to pelvic lymph nodes+ then to para.aortic nodes(2"

o pelvic nodal involvement by nternational !ederation of )ynecology and 5bstetrics staging

(!)5 stage" estimated to occur in(2"

19/ of patients with stage disease

-0/ of patients with stage disease

9/ of patients with stage diseaseo peritoneal and distant metastatic disease uncommon+ more liBely with recurrent disease (2"

>iBely risB factors8

er"ical intraepit$elial neoplasia =&:

o estimated annual incidence o- &< 2,7 per 1+000 .omen in ?aiser (ermanente$ealt$ plan =re)on+ United States> -rom 1@@7 to 2002

based on observational cohort study of 190+092 women

annual rate of routine cervical cancer screening 23 per 1+000 with rate of cytologicabnormalities 13 per 1+000

cervical intraepithelial neoplasia grade 1 ('N 1" annual incidence 132 per 1+000+highest among women aged 20.2 years (931 per 1+000"

'N 2 or 'N - annual incidence 139 per 1+000+ highest among women aged 29.2years (631 per 1+000"

eference . &m J 5bstet )ynecol 200 Jul711(1"8109o pre"ious treatment -or cer"ical intraepit$elial neoplasia )rade 3 =&< 3> associated

.it$ increased ris; o- in"asi"e cer"ical cancer


1-2+- women with severe dysplasia or cervical carcinoma in situ (e,uivalent to 'N-" in #weden from 196 to 2002+ followed for 2+-19+2 person.years

standardized incidence ratio for cervical cancer 23- (9/ ' 2316.239" compared to#wedish general female population

eference . MJ 200 Nov 27--9(42"810 Shost 8ull Tetfull.te*t+

editorial can be found in MJ 200 Nov 27--9(112"8109- Shost 8ull Teto .omen treated -or &< $a"e increased ris; -or cer"ical cancer -or at least 20 ears

based on retrospective cohort study of +94 women treated for 'N and followed for 2.2 years

invasive cervical cancer developed in 22 (03-/"+ about - times higher than incidencein general population

eference . MJ 2009 Nov 17--1(924"8116- Shost 8ull Tetfull.te*t

9uman papilloma"irus =9(> in-ection:

o $;


5/55

1+22 (1/" younger women and (-34/" older women had high.risB $;< positivityat baseline

atypia developed during follow.up in

o 6/ younger and / older women without $; in-ection associated .it$ increased ris; o-cer"ical intraepit$elial neoplasia =& and $i)$)rade s!uamous intraepit$elial lesion

=9S&B> based on systematic review limited by heterogeneity

systematic review of 1 studies with F 22+900 women comparing women with

persistent $;< infection vs3 womeno without $;< infection ( studies"

o with transient $;< infection (1- studies"o with mi*ed $;< status (11 studies"

studies (- randomized trials+ -6 cohort studies with 4 nested case.controls" varied inbaseline status of population+ deAnition of $;< persistence+ and reporting of relative risBs

persistent $;< infection associated with increased risB of cervical intraepithelialneoplasia grade 2 ('N 2"+ 'N -+ or $#> compared to women negative for $; or cervical cancer incidence 3 in 1+000 person.years in women with $< vs3 13-in 1+000 person.years in women without $< (p ? 0309"

eference . 5bstet )ynecol 2006 Jun7111(4"81-66o 9& in-ection associated .it$ increased ris; -or cer"ical )landular a*normalities


6+-42 ;ap smears of 2+1 women with $< infection and 9 women without $ancet200 Nov 107-0(9"8191

DynaMed commentary.. observational studies cannot establish oral contraceptives asdirect contributing factor

o increasin) durations o- oral contracepti"e use associated .it$ increased ris; -orcer"ical cancer

based on systematic review of mostly case.control studies

systematic review of review of 1 cohort and 2 case.control studies evaluating risBfactors in 12+9-1 women with cervical cancer

compared with never users of oral contraceptives+ '5's associated with increased risBfor cervical cancero with use ? 9 years (relative risB HI 131+ 9/ ' 131.132"

o with use 9.10 years ( 134+ 9/ ' 13.13"o with use F 10 years ( 232+ 9/ ' 13.23"

eference . >ancet 200- &pr 97-41(-4"8119 Shost 8ull Tet+ commentary

can be found in >ancet 200- May -17-41(-2"8119 Shost 8ull Tet

DynaMed commentary.. even with ad:ustments+ study cannot distinguish medication

eGects from behavioral diGerences between groupso lon)term use o- $ormonal contracepti"es ma *e associated .it$ increased ris; -or

cer"ical cancer in .omen .it$ $uman papilloma"irus in-ection

based on meta.analysis without systematic search

meta.analysis of 10 case.control studies with 1+941 patients with invasive cervical

cancer+ 22 with carcinoma in situ+ and 1+14 controls analysis limited to patients positive for human papilloma virus ($;


11/55

eference . >ancet 2002 Mar -07-9(-12"81069 Shost 8ull Tet+ editorial

can be found in >ancet 2002 Mar -07-9(-12"81060 Shost 8ull Tet

Bo.er socioeconomic status:

o lower level of education associated with increasing risB for cervical intraepithelial neoplasiagrade - ('N -" or carcinoma in -+1-- women with oncogenic $;< infection ( 'ancer 2009 Jul1710(1"841full.te*t"

Diet$lstil*estrol eposure in utero:o diethylstilbestrol e*posure in utero (%E#.e*posed daughters" has conKicting evidence for

cervical cancer risB

DS eposure in utero ma increase ris; -or cer"ical cancero based on study of ,uestionnaire responses from 9+21 %E#.e*posed daughters

aged 1.9 and medical record reviewo 109 women reported 111 cancers including 46 cervical cancerso prevalence ratio for conArmed cervical cancer 93 (9/ ' 236.39" signiAcantly

elevated compared to 2322 e*pected number of tumors (based on age and period speciAcprevalence rates"

o eference . N Engl J Med 2000 Jun 197-2(2"816-6full.te*t

DS eposure in utero ma not *e not associated .it$ cer"ical cancero based on retrospective cohort study

o ,uestionnaire and medical record review of +9-4 %E#.e*posed daughters and1+9 une*posed daughters with average 14 years follow.up and 60/ response rateo - cases of vaginal clear cell adenocarcinoma among e*posed daughters+ no

statistically signiAcant diGerences in other cancerso authors note that %E#.e*posed daughters were only average age of -6 at last

follow.up+ further surveillance needed to determine risB during menopauseo eference .J&M& 16 &ug 17260("84-0full.te*t

o diet$lstil*estrol =DS> eposure in utero associated .it$ increased li-etime ris; o-

C cer"ical intraepit$elial neoplasia )rade 2 =&< 2>

based on retrospective cohort study of +49- women e*posed to %E# in utero and1+2 women without %E# e*posure

%E# e*posure associated with increased risB of D 'N 2 compared to no e*posure(43/ vs3 -3/+ p ? 0309"

eference . N Engl J Med 2011 5ct 47-49(1"81-0

reast cancer c$emot$erap:o *reast cancer patients recei"in) c$emot$erap and al;latin) a)ent ma *e at

increased ris; -or &< compared to .omen treated .it$ oop$orectom

based on small cohort study

24 women with breast cancer previously enrolled in clinical trial evaluatingcombination chemotherapy and alBylating agent vs3 oophorectomy had cytologic andcolposcopic screening

cervical biopsies taBen if colposcopic abnormality detected

incidence of 'No -1/ (6 of 24" overallo -/ (4 of 1" among breast cancer patients treated with chemotherapy and

alBylating agent+ including 1 case of 'N 2 and 1 case of 'N -o 1/ (2 of 12" among breast cancer patients treated with oophorectomy (1/"

with 'N+ no cases of 'N 2 or 'N -

eference . r J 'ancer 1- May74(9"81062;%!

!actors not associated with increased risB8

o herpes simple* virus type 2 not associated with cervical cancer in case.control study (&m JEpidemiol 2002 5ct 197194(6"846full.te*t"

o use o- intrauterine de"ice associated .it$ reduced ris; o- cer"ical cancer

based on pooled analysis of observational studies
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11943255&dopt=Abstract&http://web.a.ebscohost.com/dynamed/DisplayEPFT?db=a9h&AN=6403027&ftt=p&site=ehost-live&direct=true&linktitle=Cervical%20cancer&currentchunkiid=114831&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&vid=3http://web.a.ebscohost.com/dynamed/DisplayEPFT?db=a9h&AN=6403027&ftt=p&site=ehost-live&direct=true&linktitle=Cervical%20cancer&currentchunkiid=114831&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&vid=3http://web.a.ebscohost.com/dynamed/DisplayEPFT?db=a9h&AN=6403027&ftt=p&site=ehost-live&direct=true&linktitle=Cervical%20cancer&currentchunkiid=114831&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&vid=3http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=11943251&http://web.a.ebscohost.com/dynamed/DisplayEPFT?db=a9h&AN=6402867&ftt=p&site=ehost-live&direct=true&linktitle=Cervical%20cancer&currentchunkiid=114831&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&vid=3http://web.a.ebscohost.com/dynamed/DisplayEPFT?db=a9h&AN=6402867&ftt=p&site=ehost-live&direct=true&linktitle=Cervical%20cancer&currentchunkiid=114831&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&vid=3http://web.a.ebscohost.com/dynamed/DisplayEPFT?db=a9h&AN=6402867&ftt=p&site=ehost-live&direct=true&linktitle=Cervical%20cancer&currentchunkiid=114831&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&vid=3http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15889450&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15889450&http://onlinelibrary.wiley.com/doi/10.1002/cncr.21129/fullhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=10866558&http://www.nejm.org/doi/full/10.1056/NEJM200006153422415http://www.nejm.org/doi/full/10.1056/NEJM200006153422415http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9718055&http://jama.jamanetwork.com/article.aspx?articleid=187878http://jama.jamanetwork.com/article.aspx?articleid=187878http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21991952&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=8494702&http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968453/pdf/brjcancer00207-0216.pdfhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968453/pdf/brjcancer00207-0216.pdfhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12370156&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12370156&dopt=Abstracthttp://aje.oxfordjournals.org/content/156/8/687.longhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11943255&dopt=Abstract&http://web.a.ebscohost.com/dynamed/DisplayEPFT?db=a9h&AN=6403027&ftt=p&site=ehost-live&direct=true&linktitle=Cervical%20cancer&currentchunkiid=114831&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&vid=3http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=11943251&http://web.a.ebscohost.com/dynamed/DisplayEPFT?db=a9h&AN=6402867&ftt=p&site=ehost-live&direct=true&linktitle=Cervical%20cancer&currentchunkiid=114831&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&vid=3http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15889450&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15889450&http://onlinelibrary.wiley.com/doi/10.1002/cncr.21129/fullhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=10866558&http://www.nejm.org/doi/full/10.1056/NEJM200006153422415http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9718055&http://jama.jamanetwork.com/article.aspx?articleid=187878http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=21991952&http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=8494702&http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968453/pdf/brjcancer00207-0216.pdfhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12370156&dopt=Abstracthttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12370156&dopt=Abstracthttp://aje.oxfordjournals.org/content/156/8/687.long


12/55

o +1 women with cervical cancer and 2+21 women without cervical cancerfrom 10 case.control studies

o 19+22 women (1-+1 human papillomavirus H$;ancet 5ncol2011 5ct712(11"864

'omplications and &ssociated 'onditions

'omplications8

Disease complications:

o lymphedema(may also be treatment related" in 1 or both lower limbs (9"

o complications due to advanced disease progression(9"

renal failure+ ureteric obstruction (from lymphadenopathy or tumor invasion"

thrombosis and hemorrhage

rectovaginal or vesicovaginal Astulas (rare"o se*ual dysfunction

many women with cervical cancer e*perience se*ual problems (disease or treatmentrelated" due to vaginal changes and@or hormonal changes including(9"

o loss of libido

o change in se*ual activity

o decreased orgasm

women who have been treated for cervical cancer more liBely than controls withoutcancer to have persistent vaginal changes that compromise se*ual activity (N Engl J Med 1May 47-0(16"81-6-full.te*t"

review of se*ual morbidity after radical hysterectomy for cervical cancer can be foundin E*pert ev &nticancer Cher 2010 Jul710("810-

omplications o- radiation t$erap:o acute radiation to*icity may include(2"

fatigue

diarrhea

irritative bladder symptoms

o acute to*icity is increased when concomitant chemotherapy is given+ especially(1+2+9"

hematologic eGects (anemia+ leuBopenia+ thrombocytopenia"

gastrointestinal eGects

o late radiation side eGects (occur D - months after completion of radiation therapy" (2+9"

small bowel obstruction

Astula

rectal bleeding

rectosigmoid stenosis

ureteric stricture

bladdero urinary fre,uency+ urgency

o dysuriao detrusor instability

o hematuriao ulceration

o about 1/ risB of radiation.related second malignancy in long.term survivors (2"
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13/55

o radiation t$erap -or cer"ical cancer associated .it$ ad"erse "a)inal c$an)es andpersistent seual pro*lems


116 patients completed validated ,uestionnaire at termination of radiation therapy forlocally advanced+ recurrent+ or persistent cervical cancer and 1+ -+ 4+ 12+ 16+ and 2 monthsafter treatment

eGects reported by patients throughout 2.year periodo low or no se*ual interest 69/o mild.to.severe dyspareunia 99/

o reduced vaginal dimension 90/o never or only occasionally able to complete se*ual intercourse 9/

o moderate.to.severe lacB of lubrication -9/o dissatisAed with their se*ual life -0/

4-/ of patients se*ually active before having cancer remained se*ually active+ butwith decreased fre,uency

eference . nt J adiat 5ncol iol ;hys 200- Jul 19794("8-o risB of pelvic fracture may be increased in older women

radiation t$erap -or cer"ical cancer associated .it$ increased rate o- pel"ic-ractures in older .omen and postmenopausal .omeno based on retrospective review

o medical records and posttreatment computed tomography ('C" scan ormagnetic resonance imaging (M" reviewed for -00 women who received radiationtherapy for cervical cancer

o pelvic fractures occurred in 2 patients (3/"+ median time to detection offracture 131 months from completion of radiation therapy

o 1- patients (9/" were symptomatic

o comparing women who developed a fracture vs3 women with no fracture

median age 9439 years vs3 43 years (p 030"

postmenopausal status 42/ vs3 -/ (p 030-"

body mass inde* 24 Bg@m2vs3 26 Bg@m2(p 030-"

o eference . 'ancer 2010 !eb 17114(-"8429full.te*t

pel"ic irradiation -or anal cancer =and possi*l -or cer"ical or rectal cancer>associated .it$ increased ris; o- pel"ic -racture in older .omen =le"el 2 midle"elEe"idence>o based on retrospective study of 4+26 women F 49 years old with pelvic

malignancies+ including 994 women with anal cancer+ 1+409 with cervical cancer+ and+24 with rectal cancer

o rates of pelvic fracture in women who had pelvic irradiation vs3 women who didnot have pelvic irradiation (nonirradiated" cervical cancer . / vs3 9/+ after ad:usting for length of follow.up+

cumulative 9.year fracture rate was 632/ vs3 93/+ hazard ratio for women withcervical cancer 1344 (p 030-"

anal cancer . 1/ vs3 9/+ after ad:usting for length of follow.up+

cumulative 9.year fracture rate was 1/ vs3 39/ rectal cancer . / vs3 /+ after ad:usting for length of follow.up+

cumulative 9.year fracture rate was 1132/ vs3 63/o eference .J&M& 2009 Nov 2-.-072(20"8296full.te*t+editorial can be found

inJ&M& 2009 Nov 2-.-072(20"824-9

&ssociated conditions8

o $< infection(4"

increased prevalence and persistence of other human papillomavirus ($;


14/55

cervical intraepithelial neoplasia associated with detection of $ associated .it$ increasedris; -or cer"ical s!uamous cell carcinoma+ e"en a-ter adustin) -or $umanpapilloma"irus =9(> serolo) and serum cotinine le"els =mar;er o- smo;in)>

based on case.control study of 126 women with invasive cervical s,uamous cell

carcinoma at least 12 months after serum collection and - matched controls ad:usted odds ratio for cervical s,uamous cell carcinoma with any

positive Chlamydiaserology was 239 (9/ ' 13.3-"

odds ratios varied for speciAc Chlamydiaserotypes

eference .J&M& 2001 Jan -7269(1"8full.te*t+ editorial can be found inJ&M& 2001Jan -7269(1"861+ commentary can be found inJ&M& 2001 &pr 7269(1-"810-

o *acterial "a)inosis ma *e associated .it$ cer"ical intraepit$elial neoplasia

based on systematic review of observational studies

systematic review of 21 studies including 11+994 women plus 1+9-+9 smearsevaluating bacterial vaginosis and cervical cancer

meta.analysis limited by signiAcant clinical and statistical heterogeneity

rates of cervical intraepithelial neoplasia were higher in women with bacterialvaginosis.positive status compared to negative status (odds ratio 1391+ 9/ ' 132.136-" inanalysis of 20 studies

eference . ;>o# 5ne 20127(10"8e9201 Shost 8ull Tetfull.te*to anal intraepithelial neoplasia andanal cancer

model .it$ 3 ris; -actors ma $elp to predict anal intraepit$elial neoplasiain .omen .it$ )enital dsplasiao based on cohort study without independent validation

o -2 women with biopsy.conArmed diagnosis of genital intraepithelial neoplasia

(vulvar+ vaginal+ or cervical" had both anal cytology and anoscopyo 134/ had anal intraepithelial neoplasia

o - risB factors associated with anal intraepithelial neoplasia

vulvar intraepithelial neoplasia H


15/55

16+204 cases of in situ or invasive cervical+ vulvar+ or vaginal

neoplasm followed for 1-6+99-+91 person.years for development of primary analcancer compared with e*pected ratios in unaGected matched controls from the generalpopulation

anal cancer developed in 299 women with gynecologic neoplasm

(aggregate standardized incidence ratio 1-34+ 9/ ' 113.193-" standardized incidence ratio for anal cancer among women with

in situ vulvar cancer 2232 (9/ ' 143.263" invasive vulvar cancer 13 (9/ ' 1139.23"

in situ cervical cancer 143 (9/ ' 1-3.132"

invasive cervical cancer 432 (9/ ' 31.63"

in situ vaginal cancer 34 (9/ ' 23.1934"

invasive vaginal cancer 136 (9/ ' 032.93-"

eference . 5bstet )ynecol 2011 Mar711(-"84-

$istory and ;hysical

$istory8

$ie- concern =>:

o

early stage disease usually asymptomatic and detected by cervical smear(-"

symptoms at presentation reported in about 14/.-2/ of women (9"

o vaginal bleeding or blood.stained vaginal discharge(-+9"

may be postcoital+ intermenstrual+ postmenopausal+ or spontaneous

ris; -or cer"ical cancer in .omen .it$ postcoital *leedin) not .ell

esta*lis$ed *ut appears lo.o based on systematic review

o -6 studies which reported or allowed calculation of prevalence or incidence ofpostcoital bleeding women in the community+ women in primary or secondary care+ orwomen with cervical cancer

o point prevalence of postcoital bleeding in community ranged from 03/ to /women+ 4/ annual cumulative incidence reported in 1 study

o prevalence of postcoital bleeding in women with cervical cancer ranged from

03/ to -/o estimated risB of cervical cancer in women with postcoital bleeding ranges

from 1 in +000 at age 20.2 years to 1 in 2+00 at age 9.9 yearso eference . r J )en ;ract 2004 Jun794(92"89-full.te*t+ commentary can be

found in &m !am ;hysician 2004 5ct 197(6"810o lymphedema in lower e*tremities (from lymphatic compression of locally invaded pelvic lymph

nodes"(9"

o pelvic pain if lymph nodes involved(-+9"

o may have bacBache(9"

Medication $istor:

o asB about use of oral contraceptives

(ast medical $istor =(M9>:

o history of abnormal cervical smear or cervical intraepithelial neoplasia

o history of infection with human papilloma viruso asB about obstetrical history

Social $istor =S9>:

o asB about early onset se*ual activity+ multiple partners+ se*ually transmitted infections (1"

o asB about history of cigarette smoBing

;hysical8
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16/55

(el"ic:

o cervical lesion may be seen on pelvic e*am(-"

o inKamed or friable cervi*+ may bleed on contact (9"

%iagnosis

MaBing the diagnosis8

o most women diagnosed as part of evaluation of abnormal ;ap smear+ with or without

symptoms (such as vaginal bleeding or other discharge"+ using colposcopically directed cervicalbiopsy(9"

o other methods of diagnosis include

cervical biopsy of grossly visible or palpable lesion

cone biopsy (via laser or cold Bnife cone" if microinvasion or early stage cervicalcarcinoma suspected

eference . 5bstet )ynecol 2002 May7(9 ;t 1"8699

see#urgery and other procedures for cervical intraepithelial neoplasia ('N" foradditional information

%iGerential diagnosis8

o Chlamydia trachomatisor other se*ually transmitted infection in women presenting with (9"

complaint of vaginal bleeding+ serosanguineous vaginal discharge+ pelvic pain

inKamed or friable cervi*o endometrial adenocarcinoma

Cesting overview8

o cervical biopsyfor diagnosis of cervical cancer

o imagingfor clinical staging and risB assessment

magnetic resonance imaging (M"

computed tomography ('C" scan

positron emission tomography (;EC" thoracic 'C scan

o surgical staging. pretreatment surgical assessment of pelvic and para.aortic lymph nodes

o sentinel lymph node biopsy

lood tests8

o serum hemoglobin (treatment for radiation.induced anemiarecommended if hemoglobin falls? 12g@d> H120 g@>I"(9"

maging studies8

Recommendations -or radiolo)ic sta)in):o #cottish ntercollegiate )uidelines NetworB (#)N" recommendations for radiologic staging of

cervical cancer

perform magnetic resonance imaging (M" on all patients with visible+ biopsy.provencervical carcinoma+ e*cept patients with stage < disease (#)N )rade "

for women with clinically apparent stage < disease+ perform postcontrast spiral ormultislice computed tomography ('C" scans of chest+ abdomen+ and pelvis ( #)N )rade "

M scan should include (#)N )rade '"

o thin section C2.weighted images perpendicular to cervi*o se,uences to include urinary tract and para.aortic nodal areas
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17/55

consider postcontrast spiral 'C as alternative to M in patients who cannot have M(#)N )rade "

for patients not suitable for surgery+ consider positron emission tomography (;EC" scan(#)N )rade '"

if imaging cannot e*clude bladder or bowel involvement+ use cystoscopy andsigmoidoscopy (do not use cystoscopy and sigmoidoscopy routinely for staging" (#)N )rade'"

ultrasound+ < urography+ and lymphangiography not recommended for staging (#)N)rade '"

o 'ancer 'are 5ntario (''5" e*pert consensus recommendations on ;EC imaging in cervicalcancer

;EC imaging recommended for women with recurrence who are candidates for pelvice*enteration or chemoradiation with curative intent

;EC imaging not recommended foro diagnosis of cervical cancer

o staging early stage cervical cancero predicting response to chemoradiation therapy

insuLcient evidence to maBe recommendation for or against ;EC imagingo for evaluation of suspected recurrence

o for staging advanced cervical cancer

eference . ''5 recommendation report on ;EC imaging in cervical cancer can be

found at''5 200 Jan 4 ;%!orNational )uideline 'learinghouse 2010 May 28191-

Radiolo)ic sta)in) o- cer"ical cancer:

o also Bnown as clinical stagingo M and 'C(1+2++9"

M preferred to 'C scan and should include pelvic and abdominal imagingo better than 'C for tumor e*tension assessment

o e,ual to 'C for nodal involvement assessment

M and 'C have low sensitivities for nodal assessment

M sensitivity improved by use of ultra.small particles of iron o*ide (=#;5" ascontrast agent

o ;EC combined with 'C the most accurate noninvasive method for detecting nodal

metastases(2+9"

o thoracic 'C scan may be useful . more accurate than chest *.ray for identifying(1+9"

pleural eGusions thoracic nodal status

parenchymal metastases

o MR& .it$ or .it$out )adolinium en$ancement ma conGrm lmp$ node metastasesin cer"ical cancer+ *ut ne)ati"e test cannot rule out lmp$ node in"ol"ement =le"el 2midle"elE e"idence>

based on systematic review of studies with clinical heterogeneity

systematic review of -2 studies with 1+02 patients with cancer assessing M forpatient level diagnosis of lymph node metastaseso cancers included rectal+ colon+ breast+ cervical+ lung+ head and necB+

esophageal+ pancreatic+ renal cell+ urinary bladder+ gall bladder+ endometrial+ ovarian+ andgastric cancers

o 9 trials of lymph node assessment in cervical cancer with 14 patients

reference standard was histopathologic e*amination

unclear blinding of inde* test results during interpretation of reference standard in

most studies

in subgroup analysis of 9 studies evaluating detection of metastasis in pelvic and para.aortic nodes+ M hado sensitivity -/ (9/ ' -/.9/"

o speciAcity 2/ (9/ ' 62/.4/"

for patient level diagnosis of lymph node metastases across all malignancies studied

o M with single malignancy criterion had 1/ sensitivity+ 66/ speciAcity in

analysis of 11 studies
http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#SIGNgradeshttp://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#SIGNgradeshttp://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#SIGNgradeshttp://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#SIGNgradeshttp://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#SIGNgradeshttp://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#SIGNgradeshttps://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=43143https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=43143http://www.guideline.gov/content.aspx?id=15193http://www.guideline.gov/content.aspx?id=15193http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef3201http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef3201http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef3201http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef4719http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef4719http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef2378http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef2378http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef2378http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef7012http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef7012http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef7012http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef4719http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef4719http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef4719http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef7012http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef7012http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef3201http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef3201http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef3201http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef7012http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9ZHluYW1lZC1saXZlJnNjb3BlPXNpdGU%3D#GenRef7012http://web.a.ebscohost.com/dynamed/detail?vid=3&sid=4f5d047b-ea5d-4e7a-b16b-b4f51855c087@sessionmgr4004&hid=4112&bdata=JnNpdGU9Z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18/55

o M with multiple malignancy criteria and no gadolinium enhancement had/ sensitivity+ 64/ speciAcity in analysis of 4 studies

o M with multiple malignancy criteria and gadolinium enhancement had 6/

sensitivity+ 62/ speciAcity in analysis of studies

eference .J Natl 'ancer nst 2010 !eb 27102("82 Shost 8ull Tetfull.te*t

o18Huorodeo)lucose (T =8DI(T> a-ter MR& ma not impro"e sur"i"al in

patients .it$ cer"ical cancer *ut ma increase detection o- etrapel"ic metastases=le"el 2 midle"elE e"idence>

based on randomized trial without blinding

12 patients (mean age 9- years" with newly diagnosed !)5 stage. ma impro"e pro)ression-ree sur"i"al compared to

sur)ical sta)in) =pretreatment sur)ical paraaortic lmp$ node assessment> in patients

.it$ locall ad"anced cer"ical cancer =le"el 3 lac;in) directE e"idence> based on nonclinical outcomes from small randomized trial

41 patients aged --.0 years with locally advanced cervical cancero randomized to clinical staging by imaging ('C scan or M" vs3 pretreatment

surgical assessment of para.aortic metastasiso further randomized in surgical group to laparoscopic vs3 e*traperitoneal

approach

trial terminated at median 96 months due to increased risB for relapse@persistence ordeath with surgical staging (hazard ratio -31-+ 9/ ' 132.436"

clinical staging associated with increased (up to 2 years posttermination"o progression.free survival (p 0300-"o overall survival (p 0302"

eference . )ynecol 5ncol 200- &pr76(1"8140

no additional trials found in 'ochrane review comparing pretreatment surgical para.aortic lymph node assessment vs3 radiologic staging in women with locally advanced cervicalcancer ('ochrane %atabase #yst ev 201- Mar 267(-"8'%00621"

o editorial discussion of M of pelvis can be found in MJ 2000 May 27-20(2"811Shost 8ull Tetfull.te*t

&ma)in) -or detectin) recurrence:

o (T'T ma *e sensiti"e and speciGc -or cer"ical cancer recurrence *ut ma not *esu*stantiall more accurate t$an MR& and'or T alone =le"el 2 midle"elE e"idence>

based on systematic review of diagnostic cohort studies with methodologic limitations
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