8132019 Cervical Excizional Treatement of Young Women

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Cervical excisional treatment of young women A

population-based study

Walter Kinney a William C Hunt b Helen Dinkelspiel c Michael Robertson b Jack Cuzick d Cosette M Wheeler be For The New Mexico HPV Pap Registry Steering Committeea Department of Womens Health and Division of Gynecologic Oncology The Permanente Medical Group Oakland CA USAb Department of Pathology University of New Mexico Health Sciences Center Albuquerque NM USAc Division of Gynecologic Oncology Columbia University College of Physicians and Surgeons New York NY USAd Wolfson Institute of Preventive Medicine Queen Mary University of London London UK e Department of Obstetrics and Gynecology University of New Mexico Health Sciences Center Albuquerque NM USA

H I G H L I G H T S

bull Biopsies of bCIN2 with HSIL cytology carried as much risk for CIN3+ on LEEP as did CIN2 with HSIL cytology

bull CIN2 and cytology bHSIL preceded more LEEPs than any other combination in every age group studied

bull The opportunity to reduce excisional harm will be lost if CIN3 and CIN2 are merged into a single histologic category

a b s t r a c ta r t i c l e i n f o

Article history

Received 1 October 2013

Accepted 26 December 2013

Available online xxxx

Keywords

Cervical screening

Colposcopy

Loop electrosurgical excision procedure (LEEP)

Cervical intraepithelial neoplasia grades 2

and 3 (CIN2 and CIN3)

Adherence to cervical treatment guidelines

Effectiveness and harms of cervical screening

Objective Assessment of cytology and biopsy results preceding cervical excisional treatment and their

association with excisional histology to evaluate compliancewith treatment recommendationsand the potential

effect of revisions in cervical histology terminology and usage

Method Datafrom a unique statewide population-based screening registrywas used to describe theuse andhis-

tologic outcomes of cervical excisional procedures in the year following an abnormal cervical screening cytologyResults From 2007 to 2011 LEEP rates decreased 87 45 and 16 for women aged 15 ndash20 21ndash24 and

25ndash29 years respectively Reductions were attributable to an overall decline in cervical screening and colposcopy

anda decreasein LEEP followinga diagnosisof less than cervical intraepithelial neoplasia grade 2 (bCIN2) or CIN2

histologypreceded by any abnormalcytology other than high-grade squamous intraepithelial lesion (bHSIL) LEEP

rates did not change signi1047297cantly (p N 07) for women aged 30ndash39 years Irrespective of age CIN2 was the most

common histologic antecedent of excisional treatment (42) with most (80) preceded by bHSIL cytology

Conclusion Cervical excisions are an unavoidable consequence of cervical screening Adherence to treatment

guidelines stipulating conservative follow-up of young women with biopsies leCIN2 could signi1047297cantly decrease

the number of excisional procedures and associated harms This opportunity will be lost if cervical intraepithelial

neoplasiagrade3 (CIN3) andsome or all of CIN2 aremerged into a singlehistologic categoryas hasbeen recently

recommended in the United States

copy 2013 The Authors Published by Elsevier Inc All rights reserved

Introduction

In March 2012 the United States Preventive Services Task Force

(USPSTF) the American Cancer Society (ACS) the American Society for

Colposcopy and Clinical Pathology (ASCCP) and the American Society

forClinical Pathology (ASCP) released newguidelines recommendingcer-

vical screening at three-year intervals starting at age 21 with the option

to substitute cytology plus human papillomavirus (HPV) DNA testing

(ldquocotestingrdquo) at 1047297ve-year intervals starting at the age of 30 The cotesting

regimen was preferred for women aged 30 years and above by all groups

except the USPSTF [1 2]

Gynecologic Oncology xxx (2014) xxxndashxxx

This is an open-access article distributed under the terms of the Creative Commons

Attribution-NonCommercial-No Derivative Works License which permits non-commercial

use distribution and reproduction in any medium provided the original author and source

are credited Condensation Adherence to treatment guidelines stipulating conservative follow-

up of youngwomenwithbiopsies leCIN2 could signi1047297cantlydecreasethe numberof exci-

sional procedures

Corresponding author at Departments of Pathology and Obstetrics and Gynecology

House of Prevention Epidemiology MSC 02-1670 Bldg 191 1816 Sigma Chi Rd NE

University of New Mexico Health Sciences Center Albuquerque NM 87131 USA Fax

+1 505 277 0265

E-mail address cwheelersaludunmedu (CM Wheeler)

YGYNO-975325 No of pages 8 4C 4 5

0090-8258$ ndash see front matter copy 2013 The Authors Published by Elsevier Inc All rights reserved

httpdxdoiorg101016jygyno201312037

Contents lists available at ScienceDirect

Gynecologic Oncology

j o u r n a l h o m e p a g e w w w e l s e v i e r c o m l o c a t e y g y n o

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These recommendations and the trend towards less screening over

a womans lifetime that hasbeen thefocus of guidelinechanges over the

past decade are driven by the recognition that screening is not without

harms and that many if not most of thelesions treated asa consequence

of screening would not have progressed to cancer [3 4] Sasieni et al

showedthat screeningwomen 20ndash24 years old has no effect on cervical

cancer incidence up to age 30 [6] For women aged 13ndash25 years in

Kaiser Northern California 68 of cervical intraepithelial neoplasia

grade 2 (CIN2) resolves spontaneously within 3 years supporting therecommendation that observation is preferred over treatment in

young women [7 8]

Concerns have been raised about risks of preterm birth premature

rupture of membranes low birth-weight and cesarean section follow-

ing cervical excisional treatment [9ndash11] In addition the discomfort

anxiety and negative impact on sexual function that have been associ-

ated with excisional treatment are of concern in circumstances where

treatment may not contribute to cancer prevention The riskbene1047297t

calculation for treatment is least favorable in young women prompting

the June 2009 Practice Improvement in Cervical Screening and

Management (PICSM) symposiumand subsequently the American Col-

lege of Obstetrics and Gynecology (ACOG) to recommend discontinuing

cervical screening in women younger than age 21 [5] Despite the low

risk for cervical precancer (cervical intraepithelial neoplasia grade 3

CIN3) and cervical cancer in young women and the potential harms of

excisional procedures studies involving provider responses to hypothet-

ical clinical scenarios suggest major deviations in cervical screening

practice from clinical practice recommendations withre1047298ex HPV testing

done for high-grade cytology testing for low-risk HPV and screening

annually with all tests regardless of the clinical situation as the most

common preference of survey respondents [12ndash15]

Prior to this assessment the association of cervical screening and

excisional treatment has never been investigated in actual practice in

the United States (US) and modeling studies are hampered by the

assumption that clinical practice guidelines are followed which the

investigations of screening practices cited above suggest may be signif-

icantly inaccurate It is also recognized that self-selection by respon-

dents to studies of clinical vignettes may not produce a representative

sample of care providers and thereby re1047298ect an imperfect view of provider compliance with guideline recommendations Using data

from a population-based statewide surveillance program we sought

to quantify the utilization of excisional treatment associated with

cervical screening by age to infer the actual indications for excisional

treatment from the antecedent cytology and biopsy diagnoses and to

examine the diagnostic yield of CIN3+ associated with different

combinations of antecedent test results

Materials and methods

The New Mexico HPV Pap Registry (NMHPVPR) is located at the

University of New Mexico and acts as a designee of the New Mexico

Department of Health (NMDOH) The NMHPVPR operates under New

Mexico Administrative Code (NMAC) 743 which speci1047297es the list of Noti1047297able Diseases and Conditions for the state of New Mexico In

2006 with the intention of monitoring cervical screening practices

and outcomes and the impact of HPV vaccination NMAC 743 speci1047297ed

thatlaboratories must report to the NMHPVPRall cervical or vaginal cy-

tology cervical pathology and HPV tests performed on women residing

in New Mexico NMAC 743 was updated in 2009 to include vulvar and

vaginal pathology (httpnmhealthorgERDhealthdatadocuments

Noti1047297ableDiseasesConditions0229121047297nalpdf ) Ongoing evaluations of

cervical screening diagnosis and treatment by the NMHPVPR have

been reviewed and approved under exempt status by the University

of New Mexico Human Research Review Committee

In this analysis we used the NMHPVPR database to investigate the

use of cervical excisional treatment over the period of 2007 through

2011 in New Mexico among women aged 15ndash

39 years The majority

(80) of cervical excisional procedures in which the method of excision

was described were identi1047297ed as loop electrosurgical excision procedure

(LEEP) When not identi1047297ed as LEEP excisional procedures were gener-

ally identi1047297ed only as cone biopsy (without specifying the excisional

method) or infrequently as cold knife conization Therefore we elected

not to attempt to stratify cervical excisional procedures by method of

excision Hysterectomy and the rarely used trachelectomy were not

included as excisional treatment for the purposes of this analysis

We evaluated the useof cervical excisional treatment by consideringthelikelihood that a woman would undergo excision within1 year of an

abnormal screening cervical cytology test with a result of atypical cells

of unknown signi1047297cance (ASC-US) or worse We de1047297ned a screening

cervical cytology test as one without any prior cervical cytology within

10 months (300 days) based on our earlier published 1047297ndings [16]

We further restricted this analysis to those screening cytology tests

without any preceding abnormal cervical cytology or histology within

15 months and without any prior excisional procedure in the database

If a woman had more than one such cervical cytology test during the

period of 2007ndash2010 we chose the earliest and refer to this as the

ldquoindexrdquo screening cytology exam A total of 39804 abnormal index

screening cytology exams were identi1047297ed as were 2236 excisional

procedures in the year following these index screens

We calculated the proportion of women undergoing excisional

treatment within 1 year of the abnormal index screening cytology

within strata de1047297ned by the cytologic result of the index screen and

the histologic result of the follow-up cervical biopsy or endocervical cu-

rettage (ECC) Abnormal cytologic results were classi1047297ed as ASC-US

[negative for high-riskHPV or HPV status unknown] ASC-US+ [positive

for high-risk HPV high risk HPV types are based on Hybrid Capture 2

(Germantown MD USA) clinical HPV assay results which detect HPV

types 16 18 31 33 35 39 45 51 52 56 58 59 and 68] low-grade

intraepithelial lesion (LSIL) atypical squamous cells-cannot rule out

high-grade (ASC-H) atypical glandular cells (AGC) and high-grade

intraepithelial lesion (HSIL) and less than HSIL (bHSIL) which included

ASC-US ASC-US+ LSIL ASC-H and AGC Cytologic results of carcinoma

were classi1047297ed as HSIL The HPVstatus of ASC-USresultswas determined

by linking the index cytology with a separate database of HPV tests

Cervical biopsy results were classi1047297ed as negative cervicalintraepithelial neoplasiagrades 1 2 and3 (CIN1 CIN2 CIN3)carcinoma

in situ (CIS) adenocarcinoma in situ (AIS) and cancer The histologic

interpretation CIN1ndash2 is included with CIN2 and CIN2ndash3 is included

with CIN3 This is believed to represent current clinical practice provides

the most charitable view of the indications for excisional treatment and

recognizes the reportedirreproducibility of these histologic designations

though it is understood that there is at present no published data about

subsequent cancer risk to validate these choices

We also computed population rates of cervical excision for the

period 2007ndash2011 These rates were computed as the number of

women treated in a given calendar year per 10000 women in the

population and also per 10000 women receiving a screening cervical

cytology test New Mexico population counts are US Census estimates

(wwwcensusgov) Using the 2007ndash2010 Centers for Disease Controlbridged-race population 1047297les 422 of NM women were non-Hispanic

white 422 were Hispanic white 30 were African American 105

were American Indian and 19 were Asian

Data analysis was conducted using SAS version 93 Con1047297dence

intervals for population excisional treatment rates are based on normal

approximation and all con1047297dence intervals for proportions are exact

Signi1047297cance testing with the CochranndashArmitage test of linear trend

was employed to discern changes over time

Results

The rate of excisional treatmentfor cervical abnormalities decreased

in New Mexico over the period 2007ndash2011 for women b30 years of age

(Table 1) The decrease was greatest for women aged 15ndash

20 years

2 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx

Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037

8132019 Cervical Excizional Treatement of Young Women

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where the excision rate declined by 87 The excision rate in womenaged 21ndash24 years decreased by 45 and in women aged 25ndash29 years

by 16 Excision rates did not change signi1047297cantly (p N 07) for

women aged 30ndash39 years Although screening rates declined over this

period excisional rates per 10000 women screened also decreased

signi1047297cantly (p b00001) for women aged 15ndash24 years

Table 2 gives the number of abnormal index cervical cytology tests

by age and result and shows thefollow-upover a period of 12 months

Follow-up has been classi1047297ed hierarchically as colposcopy with cervical

biopsy andor ECC else other gynecologic procedure else follow-up cy-

tology only else no-follow-up Other gynecologic procedures include

endometrial biopsies vaginal and vulvar biopsies and hysterectomies

A small percent (66) of women who underwent excision and had no

cervical biopsy or ECC prior to the excision are included in the

colposcopic biopsy follow-up category given that they received histo-logic evaluation of their cytologic abnormalities Colposcopies without

biopsy or ECC are not reported to the NMHPVPR

Follow-up with colposcopy and cervical biopsyECC increases with

agefor all categories of cytologic result except for ASC-US[HPV negative

or unknown] and HSIL (Fig 1) Follow-up by only repeat cytology after

an abnormal cytology of LSIL or worse wasmore common among youn-

ger women Notably 103 of women aged 15ndash20 years with HSIL

cytology were followed only by repeat cytology compared to 45 of

women aged 35ndash39 years Similarly lack of follow-up of any kind was

more common among younger women particularly among those with

LSIL or ASC-H cytology There was little change between 2007 and

2010 in the percent of women with ASC-US+ or worse cytology receiv-

ing follow-up colposcopy with biopsy except for women 15ndash20 years

ofage(Fig 2A)In this age group follow-up with colposcopy and biopsy

decreased signi1047297cantly from46 in 2007 to 26 in 2010 (p b 00001) Theproportion of women aged b 21 years with preceding abnormal cytology

was as expected and was similar to that observed for other age groups

For the period of 2007ndash2011 438 of women aged 15ndash20 years had a

prior cytology within 3 years of the screening cytology and 82 had a

prior abnormal cytology within 3 years For the more recent period of

2009ndash2011 486 had a prior cytology within 3 years of the screening

cytology and 100 had a prior abnormal cytology within 3 years

Table 3 displays thelikelihood by agecategory and overall (ages 15ndash

39 years) that a woman with a speci1047297c cervical cytology and histology

result will undergo a cervical excisional procedure in the following 12 -

months As expected excisional treatment increased with severity of

the preceding cervical histology The cytology result had no signi1047297cant

effect on the likelihood of excisional treatment for CIN2 and CIN3+ his-

tology but was a signi1047297cant factor for CIN1 and negative histology Ex-cisional treatment increased with age in all categories Table 3 reveals

the importance of the combination of a CIN2 biopsy and a cytology re-

sult less than HSIL (bHSIL) as an indication for excision The likelihood

of excision following this combination of histology and cytology results

increased from 326 at age 15ndash20 years to 678 at age 35ndash39 years

and preceded fully one-third (746 of 2236) of all excisional procedures

in women aged 15ndash39 yearsIndependent of the associated cytology re-

sult CIN2 was the most common histologic antecedent of excisional

treatment preceding 418 (935 of 2236) of all excisional treatments

Forwomenwith CIN2biopsy 74 hada prior abnormal cytology within

3 years The rate of excisional treatment for these women was 569

compared to 465 for women without prior abnormal cytology Very

few of these women had persistent CIN For the period of 2007ndash2010

32 of the 1968 women with CIN2 had CIN1 or greater on a prior biopsy

Table 1

Cervical excision (LEEP) rates in New Mexico for women 15ndash39 years old 2007ndash2011a

LEEPs per 10000 women LEEPs per 10000 women screened

Age Year LEEPs Women Rate (95 CI) Women screened Rate (95 CI)

15ndash20 years 2007 158 87944 180 (152ndash208) 21068 750 (633ndash867)

2008 118 87830 134 (110ndash159) 19735 598 (490ndash706)

2009 77 87679 88 (68ndash107) 17902 430 (334ndash526)

2010 29 87610 33 (21ndash45) 11261 258 (164ndash351)

2011 20 85420 23 (13ndash34) 7288 274 (154ndash395)

p b 00001 p b 00001

21ndash24 years 2007 278 54696 508 (449ndash568) 24272 1145 (1011ndash1280)

2008 240 54824 438 (382ndash493) 23745 1011 (883ndash1139)

2009 265 54825 483 (425ndash542) 22827 1161 (1021ndash1301)

2010 180 54941 328 (280ndash375) 21494 837 (715ndash960)

2011 160 56925 281 (238ndash325) 20550 779 (658ndash899)

p b 00001 p b 00001

25ndash29 years 2007 270 66629 405 (357ndash454) 28780 938 (826ndash1050)

2008 301 67363 447 (396ndash497) 29080 1035 (918ndash1152)

2009 329 67971 484 (432ndash536) 28457 1156 (1031ndash1281)

2010 266 68306 389 (343ndash436) 26888 989 (870ndash1108)

2011 236 69169 341 (298ndash385) 25673 919 (802ndash1037)

p = 002 p = 07

30ndash34 years 2007 185 58603 316 (270ndash361) 24438 757 (648ndash866)

2008 203 59205 343 (296ndash390) 24502 829 (715ndash942)

2009 200 61055 328 (282ndash373) 24026 832 (717ndash948)

2010 190 63234 300 (258ndash343) 23554 807 (692ndash921)

2011 210 64717 324 (281ndash368) 22392 938 (811ndash1065)p = 07 p = 007

35ndash39 years 2007 130 62665 207 (172ndash243) 23170 561 (465ndash658)

2008 132 62543 211 (175ndash247) 22936 576 (477ndash674)

2009 127 62645 203 (167ndash238) 22293 570 (471ndash669)

2010 113 61762 183 (149ndash217) 20366 555 (453ndash657)

2011 129 60634 213 (176ndash249) 19013 678 (561ndash796)

p = 08 p = 02

Total 2007 1021 330537 309 (290ndash328) 121728 839 (787ndash890)

2008 994 331765 300 (281ndash318) 119998 828 (777ndash880)

2009 998 334175 299 (280ndash317) 115505 864 (810ndash918)

2010 778 335853 232 (215ndash248) 103563 751 (698ndash804)

2011 755 336865 224 (208ndash240) 94916 795 (739ndash852)

p b 00001 p b 006

a p-Values are for test of trend in rates over the 1047297ve year period

3W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx

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within 3 years When restricting to the more recent period of 2009ndash

2010 9 of 861 women with CIN2 had a CIN1 or greater result on a

prior biopsy within 3 years The median length of follow-up for

women with CIN2 was 316 days and 90 were in the range of 62 to

350 days For comparison the median number of days between a

CIN2 biopsy and excisional treatment was 43 days

Histology results of CIN2ndash3 (n = 317) which are combined with

CIN3+ in Table 3 were followed by excision in 603 of cases which

was similar to that for CIN3+ excluding CIN2ndash3 (640) The percent

of excisions that were diagnosed as CIN3+ was also similar (555 for

CIN2ndash3 vs 645 for CIN3+ excluding CIN2ndash3)

The percentage of excisional specimens with CIN3 or greater histol-

ogy (ldquoCIN3+ yieldrdquo) is also reported in Table 3 CIN3+ yield increased

not only with the severity of the preceding histology but also with theseverity of the preceding cytology With few exceptions CIN3+ yield

from excision was signi1047297cantly greater when preceded by HSIL cytology

than by b HSIL cytology

Time trends in use of excision over the period 2007ndash2010 are shown

in Table 4 and Fig 2B strati1047297ed by age and preceding cytologyhistology

The overall use of excision decreased for women aged 15ndash24 years but

was limited to those with b HSIL cytology andor biopsy results b CIN2

Among women aged 25ndash39 years the reduction in use of excision was

seen only for those with bHSIL cytology Because of the decrease in

screening at all ages and decrease in referral to colposcopy the absolute

number of excisions decreased in all categories and age groups Notably

the proportion of LEEPs that were CIN3+ increased from 103 to 524

(p b 0∙0001) in women aged 15ndash20 years but this proportion remained

unchanged in older women (Fig 2C)

Table 2

One year follow-up of abnormal index cervical screena

Colposcopy with cervical biopsyECC Other gynecologic procedure Follow-up cytology only No follow-up

Age Cytology n

15ndash20 years ASC-US 2329 239 54 01 253 692

ASC-US+ 2643 272 288 03 220 490

LSIL 4160 427 356 04 189 451

ASC-H 316 32 497 00 168 335

HSIL 234 24 735 00 103 162

AGC 49 05 551 00 122 327

21ndash24 years ASC-US 2759 271 83 06 291 621

ASC-US+ 2839 279 508 03 163 326

LSIL 3641 358 542 04 157 298

ASC-H 441 43 578 11 127 283

HSIL 383 38 734 03 81 183

AGC 104 10 538 10 183 269

25ndash29 years ASC-US 3012 331 70 13 277 639

ASC-US+ 2303 253 580 03 157 260

LSIL 2707 297 586 07 136 271

ASC-H 444 49 658 07 101 234

HSIL 464 51 778 04 63 155

AGC 171 19 561 06 117 316

30ndash34 years ASC-US 2552 419 70 25 255 650

ASC-US+ 1268 208 644 10 109 237

LSIL 1444 237 625 06 128 241

ASC-H 323 53 684 03 121 192

HSIL 306 50 761 10 62 167AGC 196 32 602 36 117 245

35ndash39 years ASC-US 2331 494 59 37 236 668

ASC-US+ 802 170 641 21 123 214

LSIL 923 196 638 17 119 225

ASC-H 226 48 735 22 97 146

HSIL 224 47 795 22 45 138

AGC 210 45 671 52 86 190

Total ASC-US 12983 326 68 16 264 652

ASC-US+ 9855 248 494 05 167 334

LSIL 12875 323 507 06 157 330

ASC-H 1750 44 623 08 123 246

HSIL 1611 40 760 07 70 163

AGC 730 18 600 27 118 255

a Follow-up classi1047297cation is hierarchical colposcopy with cervical biopsyor endocervical curettage (ECC)else othergynecologic procedure else follow-up cytology else no follow-up

Colposcopywithout biopsyor curettage is notascertainedby theNew MexicoHPV PapRegistry(NMHPVPR) Womenwith LEEP andno precedingcolposcopy areincluded in thecolpos-

copy category Other gynecologic procedures include endometrial vaginal and vulvar biopsies and hysterectomies Follow-up cytology is de1047297ned as cervical cytology within 300 days of

the index cytology Cytologic results are as follows atypical squamous cells of unknown signi1047297cance (ASC-US) is negative for high-risk human papillomavirus (HPV) or HPV status un-knownASC-US+ is positive forhigh-risk HPVde1047297nedas positive forone or more HPVtypes including16 18 3133 35 3945 51 52 56 5859 and68 low-gradeintraepitheliallesion

(LSIL) atypical squamous cells-cannot rule out high-grade (ASC-H) atypical glandular cells (AGC) and high-grade intraepithelial lesion (HSIL)

Fig 1 Percent of women with colposcopic biopsy or endocervical curettage (ECC) within

12 months of abnormal index screeningcytology by ageof woman andresultof cytology

Cytology results are classi1047297ed as ASC-US [atypical squamous cells of undetermined

signi1047297cance negative for high-risk humanpapillomavirus (HPV)or HPV statusunknown]

ASC-US+ [ASC-US positive for high-risk HPV] LSIL [low-grade squamous intraepithelial

lesion] ASC-H[atypical squamous cells-cannot rule out high-grade] and HSIL [high-grade

squamous intraepithelial lesion]

4 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx

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8132019 Cervical Excizional Treatement of Young Women

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8132019 Cervical Excizional Treatement of Young Women

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younger age groupscould be avoideda bene1047297t of optimal adherence to

current clinical practice guidelines Importantly these data also suggest

that the proposal for changes regarding categories for cervical histology

that equateCIN3withallor part ofCIN2[24] obviates theability to man-

age CIN3 differently than CIN2 or CIN23 The newly recommended use

of p16 to in effect predict risk and clinical course does not resolve this

issue as there is no data on natural history and disease outcomes strat-

i1047297ed by p16 status and much of the p16 positive CIN2 must also be re-

gressive based on the high rates of regression observed in CIN2

unquali1047297ed by p16 testing [7 18] If these recommendations are

Table 3

LEEP within 1 year of abnormal index screen by cytological result and result of follow-up cervical biopsya

LEEP CIN3+ yield

Age Histology Cytology Screens n (95 CI) n (95 CI)

15ndash20 years CIN3+ HSIL 38 20 526 (358ndash690) 11 550 (315ndash769)

bHSIL 88 46 523 (414ndash630) 17 370 (232ndash525)

CIN2 HSIL 72 21 292 (190ndash411) 4 190 (54ndash419)

bHSIL 261 85 326 (269ndash386) 16 188 (112ndash288)

CIN1 HSIL 72 8 111 (49ndash207) 0 00 (00ndash369)

bHSIL 1401 25 18 (12ndash26) 1 40 (01ndash204)

Negative HSIL 36 2 56 (07ndash187) 0 00 (00ndash842)

bHSIL 725 2 03 (00ndash10) 0 00 (00ndash842)

No biopsy HSIL 92 4 43 (12ndash108) 1 250 (06ndash806)

bHSIL 6946 13 02 (01ndash03) 2 154 (19ndash454)

21ndash24 years CIN3+ HSIL 105 59 562 (462ndash659) 49 831 (710ndash916)

bHSIL 178 120 674 (600ndash742) 64 533 (440ndash625)

CIN2 HSIL 98 47 480 (378ndash583) 14 298 (173ndash449)

bHSIL 503 219 435 (392ndash480) 39 178 (130ndash235)

CIN1 HSIL 84 12 143 (76ndash236) 2 167 (21ndash484)

bHSIL 1989 34 17 (12ndash24) 0 00 (00ndash103)

Negative HSIL 51 10 196 (98ndash331) 4 400 (122ndash738)

bHSIL 1188 4 03 (01ndash09) 0 00 (00ndash602)

No biopsy HSIL 129 8 62 (27ndash119) 4 500 (157ndash843)

bHSIL 5842 18 03 (02ndash05) 3 167 (36ndash414)

25ndash29 years CIN3+ HSIL 155 94 606 (525ndash684) 77 819 (726ndash891)

bHSIL 217 141 650 (582ndash713) 69 489 (404ndash575)

CIN2 HSIL 123 67 545 (452ndash635) 20 299 (193ndash423)bHSIL 456 234 513 (466ndash560) 37 158 (114ndash211)

CIN1 HSIL 87 20 230 (146ndash332) 5 250 (87ndash491)

bHSIL 1562 64 41 (32ndash52) 7 109 (45ndash212)

Negative HSIL 45 11 244 (129ndash395) 4 364 (109ndash692)

bHSIL 1174 6 05 (02ndash11) 3 500 (118ndash882)

No biopsy HSIL 141 21 149 (95ndash219) 12 571 (340ndash782)

bHSIL 5141 24 05 (03ndash07) 5 208 (71ndash422)

30ndash34 years CIN3+ HSIL 121 77 636 (544ndash722) 61 792 (685ndash876)

bHSIL 156 112 718 (640ndash787) 67 598 (501ndash690)

CIN2 HSIL 59 33 559 (424ndash688) 15 455 (281ndash636)

bHSIL 242 126 521 (456ndash585) 24 190 (126ndash270)

CIN1 HSIL 35 8 229 (104ndash401) 0 00 (00ndash369)

bHSIL 968 53 55 (41ndash71) 3 57 (12ndash157)

Negative HSIL 28 9 321 (159ndash524) 5 556 (212ndash863)

bHSIL 819 7 09 (03ndash18) 1 143 (04ndash579)

No biopsy HSIL 99 13 131 (72ndash214) 8 615 (316ndash861)

b

HSIL 3562 17 05 (03ndash

08) 5 294 (103ndash

560)35ndash39 years CIN3+ HSIL 89 55 618 (509ndash719) 42 764 (630ndash868)

bHSIL 119 73 613 (520ndash701) 48 658 (537ndash765)

CIN2 HSIL 43 21 488 (333ndash645) 6 286 (113ndash522)

bHSIL 121 82 678 (587ndash760) 15 183 (106ndash284)

CIN1 HSIL 22 6 273 (107ndash502) 3 500 (118ndash882)

bHSIL 602 48 80 (59ndash104) 2 42 (05ndash143)

Negative HSIL 31 14 452 (273ndash640) 4 286 (84ndash581)

bHSIL 654 9 14 (06ndash26) 0 00 (00ndash336)

No biopsy HSIL 66 14 212 (121ndash330) 10 714 (419ndash916)

bHSIL 2969 20 07 (04ndash10) 6 300 (119ndash543)

Total CIN3+ HSIL 508 305 600 (556ndash643) 240 787 (737ndash831)

bHSIL 758 492 649 (614ndash683) 265 539 (493ndash583)

CIN2 HSIL 395 189 478 (428ndash529) 59 312 (247ndash383)

bHSIL 1583 746 471 (446ndash496) 131 176 (149ndash205)

CIN1 HSIL 300 54 180 (138ndash228) 10 185 (93ndash314)

bHSIL 6522 224 34 (30ndash39) 13 58 (31ndash97)

Negative HSIL 191 46 241 (182ndash308) 17 370 (232ndash525)

bHSIL 4560 28 06 (04ndash09) 4 143 (40ndash327)

No biopsy HSIL 527 60 114 (88ndash144) 35 583 (449ndash709)

bHSIL 24460 92 04 (03ndash05) 21 228 (147ndash328)

AlthoughLEEPSperformed within1 year of theindexcytologyaccounted forthe majority (70) some women received LEEP treatment more than 1 year after theindexcytology In the

secondyear followingthe index cytologythe percent of womenreceiving LEEP increased from 352 at 12 monthsto 39at 24 monthsfor HSIL cytologyfrom 179 to 211 forASC-H

from 53 to 67 for ASC-US+ [high-risk HPV positive] and LSIL combined from 96 to 112 for AGC and from 05 to 11 for ASC-US [high-risk HPV negative or unknown]a Histology resultis themost severediagnosis from anycervicalbiopsyor ECCdone after theindex cytology andbefore theLEEP Cytology result is themost severediagnosis from the

index cytology and any follow-upcytology done before LEEP Cervical intraepithelial neoplasia grade3 (CIN3+) includes CIN3 CIN grades 2ndash3 (CIN2ndash3) carcinoma in situ (CIS) adeno-

carcinoma in situ (AIS) and cancer cervical intraepithelial neoplasia grade 2 (CIN2) includes CIN2 and CIN grades 1ndash2 (CIN1ndash2) abbreviations for cytologic results are as outlined in

Table 2 less than high-grade squamous intraepithelial lesions (bHSIL) cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC

6 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx

Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037

8132019 Cervical Excizional Treatement of Young Women

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younger age groupscould be avoideda bene1047297t of optimal adherence to

current clinical practice guidelines Importantly these data also suggest

that the proposal for changes regarding categories for cervical histology

that equateCIN3withallor part ofCIN2[24] obviates theability to man-

age CIN3 differently than CIN2 or CIN23 The newly recommended use

of p16 to in effect predict risk and clinical course does not resolve this

issue as there is no data on natural history and disease outcomes strat-

i1047297ed by p16 status and much of the p16 positive CIN2 must also be re-

gressive based on the high rates of regression observed in CIN2

unquali1047297ed by p16 testing [7 18] If these recommendations are

Table 3

LEEP within 1 year of abnormal index screen by cytological result and result of follow-up cervical biopsya

LEEP CIN3+ yield

Age Histology Cytology Screens n (95 CI) n (95 CI)

15ndash20 years CIN3+ HSIL 38 20 526 (358ndash690) 11 550 (315ndash769)

bHSIL 88 46 523 (414ndash630) 17 370 (232ndash525)

CIN2 HSIL 72 21 292 (190ndash411) 4 190 (54ndash419)

bHSIL 261 85 326 (269ndash386) 16 188 (112ndash288)

CIN1 HSIL 72 8 111 (49ndash207) 0 00 (00ndash369)

bHSIL 1401 25 18 (12ndash26) 1 40 (01ndash204)

Negative HSIL 36 2 56 (07ndash187) 0 00 (00ndash842)

bHSIL 725 2 03 (00ndash10) 0 00 (00ndash842)

No biopsy HSIL 92 4 43 (12ndash108) 1 250 (06ndash806)

bHSIL 6946 13 02 (01ndash03) 2 154 (19ndash454)

21ndash24 years CIN3+ HSIL 105 59 562 (462ndash659) 49 831 (710ndash916)

bHSIL 178 120 674 (600ndash742) 64 533 (440ndash625)

CIN2 HSIL 98 47 480 (378ndash583) 14 298 (173ndash449)

bHSIL 503 219 435 (392ndash480) 39 178 (130ndash235)

CIN1 HSIL 84 12 143 (76ndash236) 2 167 (21ndash484)

bHSIL 1989 34 17 (12ndash24) 0 00 (00ndash103)

Negative HSIL 51 10 196 (98ndash331) 4 400 (122ndash738)

bHSIL 1188 4 03 (01ndash09) 0 00 (00ndash602)

No biopsy HSIL 129 8 62 (27ndash119) 4 500 (157ndash843)

bHSIL 5842 18 03 (02ndash05) 3 167 (36ndash414)

25ndash29 years CIN3+ HSIL 155 94 606 (525ndash684) 77 819 (726ndash891)

bHSIL 217 141 650 (582ndash713) 69 489 (404ndash575)

CIN2 HSIL 123 67 545 (452ndash635) 20 299 (193ndash423)bHSIL 456 234 513 (466ndash560) 37 158 (114ndash211)

CIN1 HSIL 87 20 230 (146ndash332) 5 250 (87ndash491)

bHSIL 1562 64 41 (32ndash52) 7 109 (45ndash212)

Negative HSIL 45 11 244 (129ndash395) 4 364 (109ndash692)

bHSIL 1174 6 05 (02ndash11) 3 500 (118ndash882)

No biopsy HSIL 141 21 149 (95ndash219) 12 571 (340ndash782)

bHSIL 5141 24 05 (03ndash07) 5 208 (71ndash422)

30ndash34 years CIN3+ HSIL 121 77 636 (544ndash722) 61 792 (685ndash876)

bHSIL 156 112 718 (640ndash787) 67 598 (501ndash690)

CIN2 HSIL 59 33 559 (424ndash688) 15 455 (281ndash636)

bHSIL 242 126 521 (456ndash585) 24 190 (126ndash270)

CIN1 HSIL 35 8 229 (104ndash401) 0 00 (00ndash369)

bHSIL 968 53 55 (41ndash71) 3 57 (12ndash157)

Negative HSIL 28 9 321 (159ndash524) 5 556 (212ndash863)

bHSIL 819 7 09 (03ndash18) 1 143 (04ndash579)

No biopsy HSIL 99 13 131 (72ndash214) 8 615 (316ndash861)

b

HSIL 3562 17 05 (03ndash

08) 5 294 (103ndash

560)35ndash39 years CIN3+ HSIL 89 55 618 (509ndash719) 42 764 (630ndash868)

bHSIL 119 73 613 (520ndash701) 48 658 (537ndash765)

CIN2 HSIL 43 21 488 (333ndash645) 6 286 (113ndash522)

bHSIL 121 82 678 (587ndash760) 15 183 (106ndash284)

CIN1 HSIL 22 6 273 (107ndash502) 3 500 (118ndash882)

bHSIL 602 48 80 (59ndash104) 2 42 (05ndash143)

Negative HSIL 31 14 452 (273ndash640) 4 286 (84ndash581)

bHSIL 654 9 14 (06ndash26) 0 00 (00ndash336)

No biopsy HSIL 66 14 212 (121ndash330) 10 714 (419ndash916)

bHSIL 2969 20 07 (04ndash10) 6 300 (119ndash543)

Total CIN3+ HSIL 508 305 600 (556ndash643) 240 787 (737ndash831)

bHSIL 758 492 649 (614ndash683) 265 539 (493ndash583)

CIN2 HSIL 395 189 478 (428ndash529) 59 312 (247ndash383)

bHSIL 1583 746 471 (446ndash496) 131 176 (149ndash205)

CIN1 HSIL 300 54 180 (138ndash228) 10 185 (93ndash314)

bHSIL 6522 224 34 (30ndash39) 13 58 (31ndash97)

Negative HSIL 191 46 241 (182ndash308) 17 370 (232ndash525)

bHSIL 4560 28 06 (04ndash09) 4 143 (40ndash327)

No biopsy HSIL 527 60 114 (88ndash144) 35 583 (449ndash709)

bHSIL 24460 92 04 (03ndash05) 21 228 (147ndash328)

AlthoughLEEPSperformed within1 year of theindexcytologyaccounted forthe majority (70) some women received LEEP treatment more than 1 year after theindexcytology In the

secondyear followingthe index cytologythe percent of womenreceiving LEEP increased from 352 at 12 monthsto 39at 24 monthsfor HSIL cytologyfrom 179 to 211 forASC-H

from 53 to 67 for ASC-US+ [high-risk HPV positive] and LSIL combined from 96 to 112 for AGC and from 05 to 11 for ASC-US [high-risk HPV negative or unknown]a Histology resultis themost severediagnosis from anycervicalbiopsyor ECCdone after theindex cytology andbefore theLEEP Cytology result is themost severediagnosis from the

index cytology and any follow-upcytology done before LEEP Cervical intraepithelial neoplasia grade3 (CIN3+) includes CIN3 CIN grades 2ndash3 (CIN2ndash3) carcinoma in situ (CIS) adeno-

carcinoma in situ (AIS) and cancer cervical intraepithelial neoplasia grade 2 (CIN2) includes CIN2 and CIN grades 1ndash2 (CIN1ndash2) abbreviations for cytologic results are as outlined in

Table 2 less than high-grade squamous intraepithelial lesions (bHSIL) cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC

6 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx

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8132019 Cervical Excizional Treatement of Young Women

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implemented (ie CIN2 and CIN3 are grouped as ldquohigh-graderdquo with the

speci1047297cation of CIN grade being optional) then reduction of the potential

harms associated with screening women in their childbearing years can

only be realized by decreasing screening itself rather than encouraging

more appropriate responses to the lesser histologic abnormalities that

precede the majority of LEEPs in the youngest women

Con1047298icts of interest statement

The authors report no con1047298icts of interest

Acknowledgments

Evaluations reported in this publication were funded by the US

National Institute of Allergy and Infectious Diseases (NIAID) and the

US National Cancer Institute (NCI) under cooperative agreements

U19AI084081 and U54CA164336 to CMW The NIAID and NCI had no

role in the study design in the collection analysis and interpretation

of data in the writing of the report and in the decision to submit

the paper for publication The content is solely the responsibility of

the authors and does not necessarily represent the of 1047297cial views of

the US National Institutes of Health The authors had full access to the

data and had 1047297nal responsibility for the decision to submit for publica-

tion The authors (WC WCH HD MR JC and CMW) had access to thedata reviewed provided input and approved the 1047297nal manuscript

submitted for publication Walter Kinney MD and Cosette Wheeler

PhD created the concept of the manuscript Walter Kinney MD and

Helen Dinkelspiel MD wrote the manuscript that was reviewed

and modi1047297ed by all authors William C Hunt performed the data extrac-

tion and analyses Members of the New Mexico HPV Pap Registry

(NMHPVPR) Steering Committee gave input to the manuscript concepts

and supported the directions of the NMHPVPR including the evaluations

presented in this manuscript The NMHPVPR Steering members partici-

pating are as follows Nancy E Joste MD University of New Mexico

Health SciencesCenter and Tricore Reference Laboratories Albuquerque

New Mexico Walter Kinney MD Kaiser Permanente Northern

California Cosette M Wheeler PhD University of New Mexico Health

Sciences Center William C Hunt MS University of New Mexico Health

Sciences Center Deborah Thompson MD MSPH New Mexico Depart-

ment of Health Susan Baum MD MPH New Mexico Department of

Health Linda Gorgos MD MSc former Medical Director of the Infectious

Disease Bureau New Mexico Department of Health Alan Waxman MD

MPH University of New Mexico Health Sciences Center David Espey

MD US Centers for Disease Control and Prevention Jane McGrath MD

University of New Mexico Health Sciences Center Steven Jenison MD

Community Member Mark Schiffman MD MPH US National Cancer

Institute Philip Castle PhD MPH Albert Einstein College of MedicineVicki Benard PhDUS Centers for Disease Control and Prevention Debbie

Saslow PhD American Cancer Society Jane J Kim PhD Harvard School

of Public Health Mark H Stoler MD University of Virginia Jack Cuzick

PhD Wolfson Institute of Preventive Medicine London Giovanna Rossi

Pressley MSc Collective Action Strategies and RWJF Center for Health

Policy at University of New Mexico and Kevin English RPh MPH

Albuquerque Area Southwest Tribal Epidemiology Center (AASTEC) No

compensation was received for contributions to this manuscript by any

named authors or by the NMHPVPR Steering Committee members

References

[1] Saslow D Soloman D Lawson HW Killackey M Kulasingam SL Cain J et alAmerican Cancer Society American Society for Colposcopy and Cervical Pathologyand American Society for Clinical Pathology screening guidelines for the preventionand early detection of cervical cancer CA Cancer J Clin 201262147ndash72

[2] Moyer VA USPreventive ServicesTaskForce Screeningfor cervical cancer USpreven-tive services taskforce recommendation statement Ann InternMed 2012156880ndash91

[3] ACOG Committee on Practice BulletinsmdashGynecology ACOG Practice Bulletin no 109cervical cytology screening Obstet Gynecol 20091141409ndash20

[4] American College of Obstetricians and Gynecologists ACOG Committee Opinion No463 cervical cancer in adolescents screening evaluation and management ObstetGynecol 2010116469ndash72

[5] Moscicki AB Cox JT Practice improvement in cervical screening and management(PICSM) symposium on management of cervical abnormalities in adolescents andyoung women J Low Genit Tract Dis 20101473ndash80

[6] Sasieni P Castanon A Cuzick J Effectiveness of cervical screening with age popula-tion based casendashcontrol study of prospectively recorded data BMJ 2009339b2968[Erratum in BMJ 2009 339b3115]

[7] Moscicki AB Ma Y Wibbelsman C et al Rate of and risks for regression of cervicalintraepithelial neoplasia 2 in adolescents and young women Obstet Gynecol

20101161373ndash

80

Table 4

Time trends in percent of abnormal index cytology followed by a LEEP within 1 yeara

15ndash24 years 25ndash39 years

Histology Cytology Year Screens LEEPs LEEPs (95 CI) Screens LEEPs LEEPs (95 CI)

CIN3+ HSIL 2007 37 20 541 (369ndash705) 98 72 735 (636ndash819)

2008 48 30 625 (474ndash760) 98 59 602 (498ndash700)

2009 31 15 484 (302ndash669) 92 49 533 (426ndash637)

2010 27 14 519 (319ndash713) 77 46 597 (479ndash708)

bHSIL 2007 76 46 605 (486ndash716) 101 70 693 (593ndash781)

2008 70 50 714 (594ndash816) 129 81 628 (538ndash711)

2009 70 38 543 (419ndash663) 128 91 711 (624ndash788)

2010 50 32 640 (492ndash771) 134 84 627 (539ndash709)

CIN2 HSIL 2007 63 21 333 (220ndash463) 59 32 542 (408ndash673)

2008 50 25 500 (355ndash645) 65 43 662 (534ndash774)

2009 28 10 357 (186ndash559) 63 30 476 (349ndash606)

2010 29 12 414 (235ndash611) 38 16 421 (263ndash592)

bHSIL 2007 237 100 422 (358ndash488) 213 117 549 (480ndash617)

2008 229 101 441 (376ndash508) 201 121 602 (531ndash670)

2009 166 67 404 (328ndash482) 202 110 545 (473ndash615)

2010 132 36 273 (199ndash357) 203 94 463 (393ndash534)

CIN1 negative no biopsy HSIL 2007 167 21 126 (80ndash186) 172 33 192 (136ndash259)

2008 123 11 89 (45ndash154) 141 33 234 (167ndash313)

2009 103 9 87 (41ndash159) 134 28 209 (144ndash288)

2010 71 3 42 (09ndash119) 107 22 206 (134ndash295)

bHSIL 2007 5122 32 06 (04ndash09) 4686 97 21 (17ndash25)

2008 4843 35 07 (05ndash10) 4411 72 16 (13ndash21)

2009 4613 16 03 (02ndash06) 4376 43 10 (07ndash13)2010 3513 13 04 (02ndash06) 3978 36 09 (06ndash13)

a Histologyresult is themost severe diagnosis from anycervicalbiopsyor ECCdone after theindex cytologyand beforethe LEEP Cytology result is themost severe diagnosis from the

indexcytologyand any follow-up cytology donebefore LEEPAbbreviations are as detailed for Table 3 CIN3+ includes CIN3 CIN2ndash3 CIS AIS andcancerCIN2 includes CIN2 andCIN1ndash2

bHSIL cytology includes ASC-US ASC-US+ LSIL ASC-H and AGC

7W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx

Please cite this article asKinneyW et alCervical excisional treatment of young womenA population-based study Gynecol Oncol (2014)http dxdoiorg101016jygyno201312037

8132019 Cervical Excizional Treatement of Young Women

httpslidepdfcomreaderfullcervical-excizional-treatement-of-young-women 88

[8] Wright Jr TC Massad LS Dunton CJ Spitzer M Wilkinson EJ Solomon D 2006ASCCP-Sponsored Consensus Conference 2006 consensus guidelines for the man-agement of women with abnormal cervical screening tests J Low Genit Tract Dis200711201ndash22 [Erratum in J Low Genit Tract Dis 2008 12 255]

[9] Kyrgiou M Koliopoulos G Martin-Hirsch P Arbyn M Prendiville WParaskevaidis E Obstetric outcomes after conservative treatment forintraepithelial or early invasive cervical lesions systematic review and meta-analysis Lancet 2006367489ndash98

[10] Sadler L Saftlas A Wang W Exeter M Whittaker J McCowan L Treatmentfor cervical intraepithelial neoplasia and risk of preterm delivery JAMA20042912100ndash6

[11] Samson SL Bentley JR Fahey TJ McKay DJ Gill GH The effect of loop electro-surgical excision procedure on future pregnancy outcome Obstet Gynecol2005105325ndash32

[12] Yabroff KRSaraiya M Meissner HI HaggstromDA Wideroff L Yuan G et al Special-ty differences in primary care physician reports of Papanicolaou test screeningpractices a national survey 2006 to 2007 Ann Intern Med 2009151602ndash11

[13] Lee JW Berkowitz Z Saraiya M Low-risk human papillomavirus testing and othernonrecommended human papillomavirus testing practices among US health careproviders Obstet Gynecol 20111184ndash13

[14] Roland KB Soman A Benard VB Saraiya M Human papillomavirus and Papanicolaoutests screening interval recommendations in the United States Am J Obstet Gynecol2011205447e1ndash8

[15] Saraiya M Berkowitz Z Yabroff KR Wideroff L Kobrin S Benard V Cervical cancerscreening with both human papillomavirus and Papanicolaou testing vsPapanicolaou testing alone what screeningintervals are physicians recommendingArch Intern Med 2010170977ndash85

[16] Wheeler CM Hunt WC Cuzick J et al A population-based study of human papillo-mavirus genotype prevalence in the United States baseline measures prior tomass human papillomavirus vaccination Int J Cancer Jan 1 2013132(1)198ndash207

[17] CastlePE SchiffmanM Wheeler CMSolomon D Evidence forfrequent regression of cervical intraepithelial neoplasia-grade 2 Obstet Gynecol 200911318ndash25

[18] Robertson AJ Anderson JM Beck JS et al Observer variability in histopathologicalreporting of cervical biopsy specimens J Clin Pathol 198942231ndash8

[19] Wright Jr TC MassadLS DuntonCJ SpitzerM Wilkinson EJSolomonD 2006AmericanSociety for Colposcopy and Cervical Pathology-sponsored Consensus Conference 2006consensus guidelines for the management of women with cervical intraepithelialneoplasia or adenocarcinoma in situ J Low Genit Tract Dis 200711223ndash39

[20] Pretorius RG Zhang WH Belinson JL et al Colposcopically directed biopsy randomcervical biopsy and endocervical curettage in the diagnosis of cervical intraepithelialneoplasia II or worse Am J Obstet Gynecol 2004191430ndash4

[21] Stoler MH Vichnin MD Ferenczy A et al FUTURE I II and III Investigators Theaccuracy of colposcopic biopsy analyses from the placebo arm of the Gardasilclinical trials Int J Cancer 20111281354ndash62

[22] Cox JT More questions about the accuracy of colposcopy what does this mean forcervical cancer prevention Obstet Gynecol 20081111266ndash7

[23] Pretorius RG Belinson JL Burchette RJ Hu S Zhang X Qiao YL Regardless of skillperforming more biopsies increases the sensitivity of colposcopy J Low GenitTract Dis 201115180ndash8

[24] Darragh TM Colgan TJ Cox JT et al LAST Project Work Groups The LowerAnogenital Squamous Terminology Standardization Project for HPV-Associated Le-sions background and consensus recommendations from the College of AmericanPathologists and the American Society for Colposcopy and Cervical Pathology JLow Genit Tract Dis 201216205ndash42

8 W Kinney et al Gynecologic Oncology xxx (2014) xxxndash xxx

Pleasecite this article as KinneyW et al Cervical excisional treatment of young womenA population-based study Gynecol Oncol (2014) http dxdoiorg101016jygyno201312037