Protocol for the Reporting of Cervicovaginal Cytology Specimens

Version: 1.0.0.0
Protocol Posting Date: June 2022
The use of this protocol is recommended for clinical care purposes but is not required for accreditation
purposes.

This protocol may be used for the following:

Procedure Description
Cervicovaginal cytology Includes broom, spatula, and endocervical brush collection methods
Specimen Type Description
PAP stained cervicovaginal cytology

The following should NOT be reported using this protocol:

Specimen
Non-cervicovaginal cytology specimens

Authors
Sana O. Tabbara, MD*; George G. Birdsong, MD; Christine N. Booth, MD; Jennifer Brainard, MD; Stuart
E. H. Cameron, MD; James Dvorak; Abha Goyal, MD; Lananh Nguyen, MD; Kaitlin Sundling, MD, PhD.
With guidance from the CAP Cancer and CAP Pathology Electronic Reporting Committees.
* Denotes primary author.

Accreditation Requirements
The use of this case summary is recommended for clinical care purposes but is not required for
accreditation purposes. The core and conditional data elements are routinely reported. Non-core data
elements are indicated with a plus sign (+) to allow for reporting information that may be of clinical value.

Includes The Bethesda System (TBS) 2014 terminology for reporting cervicovaginal cytology specimens.

© 2022 College of American Pathologists (CAP). All rights reserved. For Terms of Use please visit www.cap.org/cancerprotocols . 1
CAP Approved Cervicovaginal.Cyto_1.0.0.0.REL_CAPCP

Summary of Changes
v 1.0.0.0
• New Protocol

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Reporting Template
Protocol Posting Date: June 2022
Select a single response unless otherwise indicated.

CASE SUMMARY: (Protocol for the Reporting of Cervicovaginal Cytology Specimens)

This case summary may be useful for clinical care purposes but is not required for accreditation purposes. Core data elements are
bolded to help identify routinely reported elements. (Note A)

PATIENT INFORMATION

Age: _________________

Gender (Note B)
___ Male
___ Female
___ Other (specify): _________________

Collection Date: _________________

Date of Last Menstrual Period (if applicable): _________________

Indication for Examination

___ Screening, routine
___ Screening, high-risk
___ Diagnostic
___ Reflex cytology following positive primary HPV screening result

Prescription Drugs (select all that apply)

___ None
___ Unknown
___ Hormone replacement therapy (estrogen / progesterone)
___ Androgen therapy
___ Oral contraceptive drugs
___ Chemotherapeutic agents
___ Other (specify): _________________

Clinical History (select all that apply)

___ Unknown
___ Pregnant
___ Post-partum
___ Hysterectomy
___ Total
___ Supracervical
___ Prior radiation therapy
___ Diethylstilbesterol (DES) exposure
___ Intrauterine device (IUD)
___ Post-menopausal bleeding

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___ Abnormal bleeding

___ Vaginal discharge
___ Other (specify): _________________

History of Dysplasia or Malignancy

___ Unknown
___ Negative
___ Positive
___ Abnormal Pap tests / Dysplasia, NOS
___ Low-grade squamous intraepithelial lesion (LSIL)
___ High-grade squamous intraepithelial lesion (HSIL)
___ Endocervical adenocarcinoma in situ (AIS)
___ Squamous cell carcinoma
___ Adenocarcinoma
___ Other (specify): _________________
___ Carcinoma, NOS

High-Risk Human Papillomavirus (HPV) History (select all that apply)

___ Unknown
___ Negative
___ Positive for high risk
___ Positive genotype 16
___ Positive genotype 18
___ Positive for genotype 16/18
___ Positive for genotype 18/45
___ Other high-risk types (specify, if known): _________________
___ Date of first positive (if available): _________________
___ Date of most recent HPV testing: _________________

HPV Vaccination History (Note C)

___ Unknown
___ Unvaccinated
___ Vaccinated
+___ Completed
+___ Incomplete
+___ Quadravalent
+___ Nonavalent
+___ Other (specify): _________________

+Human Immunodeficiency Virus (HIV) Status

___ Unknown
___ Negative
___ Positive
___ Positive but undetected

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PREANALYTICAL EXAMINATION OF THE SPECIMEN

Source
___ Cervical
___ Vaginal
___ Other (specify): _________________

+Sampling Device
___ Broom
___ Spatula / Endocervical Brush
___ Unknown
___ Other (specify): _________________

Test(s) Ordered
___ Pap test only
___ Cotesting
___ Reflex cytology following positive primary HPV screening result

Gross Description (select all that apply)

___ Number of conventional smear slides: _________________
___ Liquid-based in fixative
Color (specify): _________________
Approximate Volume: _________________ ml
___ Other (specify): _________________

Preparation Type
___ Conventional
___ Liquid-based ThinPrep
___ Liquid-based SurePath
___ Other (specify): _________________

Number of Slides Prepared (specify): _________________

+Liquid-based Imaging System Type

___ ThinPrep Imaging System
___ BD FocalPoint GS
___ Other (specify): _________________

INTERPRETATION

Specimen Adequacy (Note D)

___ Satisfactory for evaluation
Quality Indicators
___ Transformation zone present
___ Transformation zone absent
___ Not applicable
___ Cannot be determined

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___ Unsatisfactory for evaluation

___ Processed and examined
___ Insufficient squamous cellularity
___ Obscuring blood
___ Obscuring inflammation
___ Obscuring acellular material
___ Other (specify): _________________
___ Not processed (explain): _________________

Results (select all that apply)

___ Negative for intraepithelial lesion or malignancy (NILM)
___ Negative for squamous intraepithelial lesion
+Non-Neoplastic Cellular Variations (select all that apply)
___ Squamous metaplasia
___ Keratotic changes
___ Tubal metaplasia
___ Atrophy
___ Pregnancy-associated changes
___ Other (specify): _________________
Reactive Cellular Changes (Note E)
___ Present
+___ Inflammation (includes typical repair)
+___ Lymphocytic (follicular) cervicitis
+___ Radiation
+___ Intrauterine device (IUD)
+___ Glandular cells status post-hysterectomy
+___ Other (specify): _________________
___ Absent
___ Squamous cell abnormalities
Squamous Cell Abnormalities
___ Atypical squamous cells - undetermined significance (ASC-US)
___ Atypical squamous cells cannot exclude HSIL (ASC-H)
___ Low-grade squamous intraepithelial lesion (LSIL)
___ High-grade squamous intraepithelial lesion (HSIL)
___ High-grade squamous intraepithelial lesion (HSIL) with features suspicious for invasion
___ Squamous cell carcinoma
___ Other (specify): _________________
___ Glandular cell abnormalities
Glandular Cell Abnormalities
___ Atypical endocervical cells (NOS or specify): _________________
___ Atypical endometrial cells: _________________
___ Atypical glandular cells (NOS or specify): _________________
___ Atypical glandular cells, favor neoplastic
___ Atypical endocervical cells, favor neoplastic
___ Endocervical adenocarcinoma in situ
___ Endocervical adenocarcinoma
___ Endometrial adenocarcinoma

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___ Extrauterine adenocarcinoma

___ Adenocarcinoma NOS
___ Other (specify): _________________
___ Other malignant neoplasms (specify): _________________

Other Significant Findings (select all that apply)

___ Endometrial cells present (in patients 45 years of age or older)
___ Trichomonas vaginalis
___ Fungal organisms morphologically consistent with Candida species
___ Shift in flora suggestive of bacterial vaginosis
___ Bacteria morphologically consistent with Actinomyces species
___ Cellular changes consistent with herpes simplex virus
___ Cellular changes consistent with cytomegalovirus
___ Other (specify): _________________
___ None identified

ANCILLARY TESTING
Please complete all available test results associated with the current Pap test

HR-HPV (select all that apply)

___ Not performed
___ Negative
___ Positive (not otherwise specified)
___ Positive for genotype 16
___ Positive for genotype 18
___ Positive for genotype 18/45
___ Positive for other high-risk types (specify): _________________
___ Positive for unknown subtype
___ Pending at the time of cytologic evaluation

HR-HPV Test Platform

___ BD Onclarity TM HPV Assay
___ Hologic Cervista
___ Hologic Aptima
___ Qiagen Digene Hybrid Capture 2 (HC2)
___ Roche cobas 4800
___ Roche cobas 6800/8800
___ Laboratory-developed method
___ DNA
___ RNA
___ Other (specify): _________________
___ Other (specify): _________________

+Neisseria gonorrhoeae
___ Negative
___ Positive

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+Chlamydia trachomatis
___ Negative
___ Positive

+Trichomonas vaginalis
___ Negative
___ Positive

+Herpes Simplex Virus (HSV) (select all that apply)

___ Negative
___ Positive (not otherwise specified): _________________
___ Positive for HSV-1
___ Positive for HSV-2

+Immunocytochemistry (select all that apply)

___ P16: _________________
___ Ki-67: _________________
___ Other (specify): _________________

+Other Tests Performed (specify): _________________

+Concurrent Biopsy
___ Yes
___ No
COMPUTER-ASSISTED INTERPRETATION OF CERVICAL CYTOLOGY
+Specify Device: _________________
+Specify Results: _________________

COMMENTS

Comment(s): _________________

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Explanatory Notes

A. Introduction
The aim of this protocol is to improve the completeness, clarity, and portability of Pap test reporting, while
being mindful of the wide range of practice settings in which the data in the report is generated and
disseminated. This report includes the Bethesda System for reporting Cervical Cytology1 which is widely
used standardized terminology and incorporate clinical and ancillary testing results that have already
been integrated into daily practice, as outlined in the ASCCP guidelines.2 It also takes into consideration
the introduction of additional testing recommendations and modalities in the future.3,4

The protocol is based upon input from past and present members of the CAP Cytopathology Committee
and prepared in conjunction with the CAP Pathology Electronic Reporting Committee.

This reporting format is meant to replace the final report and will be adapted to laboratory information
systems to facilitate utilization and provide more easily reproducible and extractable data. The
construction of this protocol does allow for the insertion of pertinent additional information when available.
It may be used as a guide for trainees and pathologists who may only perform a limited number of Pap
tests in their practice. The committee hopes this is a first step in providing a general framework for more
standardized quality Pap reporting practice.

The content of the protocol represents the consensus opinion of the CAP Cytopathology Committee and
the CAP Pathology Electronic Reporting Committee. It is the Committees’ recommendation that all
available elements be included.

References
1. Nayar R, DC Wilbur, Eds The Bethesda System for Reporting Cervical Cytology,
3rd. edition. New York, NY: Springer 2015.
2. Perkins RB, Guido RS, Castle PE, et al. 2019 ASCCP Risk-Based Management Consensus
Guidelines for abnormal cervical cancer screening tests and cancer precursors. J Low Genit Tract
Dis 24: 102–131, 2020
3. Fontham ETH, Wolf AMD, Church TR, et al. Cervical Screening for Individuals at Average
Risk: 2020 Guideline Update from the American Cancer Society. Cancer J Clin 2020, 0:1-26 c
2020 American Cancer Society
4. US Preventive Services Task Force. Screening for Cervical Cancer: US Preventive Services Task
Force Recommendation Statement. JAMA. 2018;320(7):674–686. doi:10.1001/jama.2018.10897

B. Gender
In cervical cancer screening, it is important to recognize the importance of using inclusive gender
terminology within the pathology report. Individuals at risk for cervical cancer may identify as women,
men, or other non-binary or gender fluid terms.

Laboratory information systems should accurately convey the patient’s gender identity on reports. At
minimum, a nonbinary option such as “Other” is recommended to be included, ideally allowing the patient
to self-describe their gender identity. Laboratory information systems may also record the sex assigned at
birth, which would be kept separately from the gender identity.1 Ideally, patients would be offered the
opportunity to update this information at any time they choose, such as through an online patient portal or
at appointments. If pronouns are used in the pathology report, “they/them/theirs” pronouns are

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recommended if patient-identified pronouns are not indicated. Care should be taken not to assume
“she/her/hers” pronouns on Pap test reporting.

While this form is developed specifically for cervical and vaginal sources (of natal organs), it is also
recognized that patients with a neovagina are also at risk of HPV infection, and Pap test screening is
recommended.2,3 Neovaginal specimens may be considered non-gynecologic in origin; however, many
aspects of this reporting form may still apply. A neovaginal specimen source should be specifically
indicated, when known to the collecting clinician.

References
1. Gamelin M. Guide to LGBTQ+ Inclusive Forms. Accessed January 17, 2022.
https://denverptc.org/resource.php?id=231
2. Grosse A, Grosse C, Lenggenhager D, Bode B, Camenisch U, Bode P. Cytology of the
neovagina in transgender women and individuals with congenital or acquired absence of a natural
vagina. Cytopathology. 2017;28(3):184-191. doi:10.1111/cyt.12417
3. Garcia MM. Cancer screening in the transgender population: a review of current guidelines, best
practices, and a proposed care model. Transl Androl Urol. 2020;9(6):2771-2785.
doi:10.21037/tau-20-954

C. HPV Vaccination
Human papillomavirus (HPV) is a common sexually transmitted viral infection that affects multiple sites,
commonly the reproductive organs. In females, the virus causes cancer of the cervix, vulva, and vagina
whereas in males, it causes cancer of the penis. For both genders, it causes cancer of the anus and
oropharynx. HPV infection also causes benign lesions, such as anogenital warts and respiratory
papillomatosis. Although there are many types of HPV, studies have identified key genotypes associated
with disease. HPV 16 and 18 are two specific genotypes associated with cancer and are considered high
risk types.1

Currently, there are three vaccines approved by the United States Food and Drug
Administration. Nonavalent, (Gardasil 9, 9vHPV), quadrivalent, (Gardasil 4, 4vHPV), and bivalent
(Cervarix, 2vHPV). All three vaccines protect against high risk HPV types 16 and 18 with specific targets
to the L1 protein. Quadrivalent vaccine includes additional targets to HPV 6 and 11. Nonavalent vaccine
includes targets to HPV 6, 11, 31, 33, 45, 52, and 58. Nonavalent vaccine is only distributed in the United
States. Both bivalent and nonavalent vaccines are distributed in Canada and all three are distributed in
Europe.2

The recommended dosing for the vaccination is based on the patient’s age at administration and patient’s
history.3 Two doses are required for patients who received the first dose before they turn 15. Three
doses are required for a) patients who received two doses less than 5 months apart when they are
between 9 and14 years old OR b) patients are between 9 and 26 years old with weakened immune
systems. Vaccination is not recommended for patients older than 26 years old.

References
1. Human Papillomavirus (HPV) Vaccination: What Everyone Should Know.
https://www.cdc.gov/vaccines/vpd/hpv/public/index.html

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2. European Medicine Agency, Human papillomavirus vaccines, Cervarix, Gardasil, Gardasil 9,

Silgard. https://www.ema.europa.eu/en/documents/referral/hpv-vaccines-article-20-procedure-
assessment-report_en.pdf
3. National Advisory Committee on Immunization (NACI). Update on Human Papillomavirus (HPV)
Vaccines. An Advisory Committee Statement (ACS). Canada Communicable Disease Report.
January 2012;Volume 38, ACS-1:1-62.

D. Specimen Adequacy
Adequacy criteria were set forth in The Bethesda System (TBS)1 to provide criteria and protocols to
promote the consistent assessment of the adequacy of cervical and anal cytology specimens. In the
absence of such criteria, individual laboratories would need to develop their own adequacy criteria which
would probably lead to greater inconsistency in the percent of cases flagged as unsatisfactory or
suboptimal across laboratories.

Specimen Cellularity
Cellularity thresholds are based on limited scientific evidence. One study has suggested that liquid-based
preparations (LBP) with fewer than 5000-20,000 cells may have a higher risk of being false negative
(FNP),2,3 however this has not been confirmed. TBS states that an LBP from a woman with a cervix
should have an estimated minimum of 5000 well-preserved, well-visualized, nucleated squamous cells to
be considered adequate.1 This threshold is provided to promote the usage of consistent criteria across
laboratories however, it is not meant to be rigidly applied. Exceptions to this guideline are women with a
history of chemo or radiation therapy for cancer, or who are post-hysterectomy or post-menopausal with
atrophic changes. The patient’s history must be taken into account in assessing adequacy, but specimens
with less than or equal to 2000 cells should usually be considered unsatisfactory.

Cytologists should not attempt to manually count cells to determine cellularity.1 The cellularity of LBP can
be estimated by counting the number of cells in multiple high-power fields (HPFs), usually 40X, across
the diameter of the preparation. The two commercially available LBPs, ThinPrep (Hologic), and SurePath
(BD) deposit the cells in circles of different diameters and have different cellular densities. ThinPrep
deposits cells in a 20 mm diameter circle whereas the SurePath circle is 13 mm. The number of cells/HPF
that correspond to the 5000 cell minimum is therefore different. This number is also affected by the field
number (FN) of the eyepieces of the microscope. Table 1 displays the number of cells/HPF for different
combinations of eyepiece field number, objective power, and circle diameter.1

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Table 1. Guidelines for Estimating Cellularity of Liquid-Based Preparations

FN20 eyepiece/10X objective
Prep. diameter (mm) Area (mm2) Number of fields at FN20, Number of cells/field for
10X 5K total
13 132.7 42.3 118.3
20 314.2 100 50
FN20 eyepiece/40X objective
Prep. diameter (mm) Area (mm2) Number of fields at FN20, Number of cells/field for
40X 5K total
13 132.7 676 7.4
20 314.2 1600 3.1
FN22 eyepiece/10X objective
Prep. diameter (mm) Area (mm2) Number of fields at FN22, Number of cells/field for
10X 5K total
13 132.7 34.9 143.2
20 314.2 82.6 60.5
FN22 eyepiece/40X objective
Prep. diameter (mm) Area (mm2) Number of fields at FN22, Number of cells/field for
40X 5K total
13 132.7 559 9
20 314.2 1322 3.8
FN=field number.

Conventional preparations should contain a minimum of 8000-12,000 well-preserved, well-visualized

cells. As with LBP, cellularity should be estimated and not considered a rigid threshold. It is not necessary
to count cells on conventional preparations. Cellularity can be estimated by comparing representative
fields with the computer edited reference images in the Bethesda System for Reporting Cervical
Cytology.1

Endocervical/Transformation Zone Component

TBS states that an adequate T-zone sample requires at least 10 well preserved endocervical or
squamous metaplastic cells, singly or in clusters. The presence of a transformation zone or endocervical
component (T-zone) is not necessary for a specimen to be considered adequate. Theoretically, it might
be expected that the risk of an FNP specimen would be elevated if a T-zone component were absent
since squamous intraepithelial lesions are thought to arise in the T-zone. Some studies have shown that
endocervical cells are more likely to be present in specimens with squamous intraepithelial
lesions,4,5,6 however other studies have shown that specimens which lack endocervical cells are not
significantly more likely to be FNP, and in fact, some studies show a trend toward a lower risk of
FNP.7,8,9,10,11 While these observations may be somewhat confusing, the co-presence of endocervical
cells and dysplastic cells in specimens does not by itself indicate that specimens which lack endocervical
cells have a higher risk of being FNP. Nevertheless, the presence of the T-zone component is considered
an important quality indicator. Lack of endocervical cells indicates that the endocervical region has not
been well sampled, possibly increasing the risk of missing an endocervical lesion such as
adenocarcinoma-in-situ or adenocarcinoma.1

Obscuring Factors
Excessive blood or inflammation may obscure epithelial cells in Pap tests. A specimen should be deemed
unsatisfactory when more than 75% of the squamous cells are obscured unless abnormal cells are

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identified. If 50-75% of cells are obscured, a comment describing the specimen as partially obscured
should be added following the satisfactory term. The percentage of cells obscured, not the area of the
slide, is what is assessed. Minimal cellularity criteria should also be applied.1

Interfering Substances
Excessive blood or lubricants that contain carbomers or carbopol polymers can interfere with ThinPreps
by clogging the filter thereby reducing the cellularity of the specimen.12,13 Some specimens which are
unsatisfactory due to blood can be successfully reprocessed utilizing dilute glacial acetic acid.14,15 The
unsatisfactory rate can be reduced by 50% or more with this technique, but it interferes with some types
of HPV tests. Interfering substances have little or no effect on SurePath specimens.16,17,18

References
1. Birdsong G, Davey D. Specimen Adequacy. In: Nayar R, Wilbur D, editors. The Bethesda System
for Reporting Cervical Cytology; Definitions, Criteria, and Explanatory Notes. Third ed. New York:
Springer; 2015. p. 1-28.
2. Bolick DR, Kerr J, Staley BE, et al. Effect of cellularity in the detection rates of high grade and low
grade squamous intraepithelial lesions. Acta Cytol. 2002;46:922-3.
3. Martin-Hirsch P, Lilford R, Jarvis G, Kitchener HC. Efficacy of cervical-smear collection devices: a
systematic review and meta-analysis. Lancet. 1999;354(9192):1763-70.
4. Baer A, Kiviat NB, Kulasingam S, Mao C, Kuypers J, Koutsky LA. Liquid-based Papanicolaou
smears without a transformation zone component: should clinicians worry? Obstet Gynecol.
2002;99(6):1053-9.
5. Bos AB, van Ballegooijen M, Elske van den Akker-van Marle M, Hanselaar AG, van Oortmarssen
GJ, Habbema JD. Endocervical status is not predictive of the incidence of cervical cancer in the
years after negative smears. Am J Clin Pathol. 2001;115(6):851-5.
6. Kivlahan C, Ingram E. Papanicolaou smears without endocervical cells. Are they inadequate?
Acta Cytol. 1986;30(3):258-60.
7. Mitchell H, Medley G. Longitudinal study of women with negative cervical smears according to
endocervical status. Lancet. 1991;337(8736):265-7.
8. Mitchell HS. Longitudinal analysis of histologic high-grade disease after negative cervical cytology
according to endocervical status. Cancer. 2001;93(4):237-40.
9. Mintzer M, Curtis P, Resnick JC, Morrell D. The effect of the quality of Papanicolaou smears on
the detection of cytologic abnormalities. Cancer. 1999;87(3):113-7.
10. Vooijs PG, Elias A, van der Graaf Y, Veling S. Relationship between the diagnosis of epithelial
abnormalities and the composition of cervical smears. Acta Cytol. 1985;29(3):323-8.
11. Studeman KD, Ioffe OB, Puszkiewicz J, Sauvegeot J, Henry MR. Effect of cellularity on the
sensitivity of detecting squamous lesions in liquid-based cervical cytology. Acta Cytol.
2003;47(4):605-10.
12. Feit TD, Mowry DA. Interference potential of personal lubricants and vaginal medications on
ThinPrep pap tests. J Am Board Fam Med. 2011;24(2):181-6.
13. Lin SN, Taylor J, Alperstein S, Hoda R, Holcomb K. Does speculum lubricant affect liquid-based
Papanicolaou test adequacy? Cancer cytopathology. 2014;122(3):221-6.
14. Bentz JS, Rowe LR, Gopez EV, Marshall CJ. The unsatisfactory ThinPrep Pap Test: missed
opportunity for disease detection? American Journal of Clinical Pathology. 2002;117(3):457-63.
15. Haack LA, O'Brien D, Selvaggi SM. Protocol for the processing of bloody cervical specimens:
glacial acetic acid and the ThinPrep Pap Test. Diagn Cytopathol. 2006;34(3):210-3.

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16. Kenyon S, Sweeney BJ, Happel J, Marchilli GE, Weinstein B, Schneider D. Comparison of BD
Surepath and ThinPrep Pap systems in the processing of mucus-rich specimens. Cancer
Cytopathol. 2010;118(5):244-9.
17. Owens CL, Peterson D, Kamineni A, Buist DS, Weinmann S, Ross TR, et al. Effects of
transitioning from conventional methods to liquid-based methods on unsatisfactory Papanicolaou
tests: results from a multicenter US study. Cancer Cytopathol. 2013;121(10):568-75.
18. Sweeney BJ, Haq Z, Happel JF, Weinstein B, Schneider D. Comparison of the effectiveness of
two liquid-based Papanicolaou systems in the handling of adverse limiting factors, such as
excessive blood. Cancer. 2006;108(1):27-31.

E. Reactive Cellular Changes

The Bethesda 2014 classification system for cervical cytology includes the subcategory of “Reactive
Cellular Changes” under the Pap test reporting category “Negative for Intraepithelial Lesion or
Malignancy”.1

The cells in the Pap test can undergo reactive changes associated with inflammation (including typical
repair and lymphocytic cervicitis), radiation, and changes associated with intrauterine contraceptive
devices. These changes can be a part of normal reactive changes and do not represent dysplastic or
precancerous changes.

The reactive cells seen in repair or associated with inflammation can show an increase in nuclear size,
presence of nucleoli, binucleation, cytoplasmic vacuolization, and polychromasia. A majority of reactive
cells are of metaplastic origin but can also be seen in mature squamous cells or columnar epithelial
cells.2 The nuclei are usually non-overlapping and have an even and uniform fine granular chromatin.
Small perinuclear halos can also be present but do not have peripheral thickening. The reactive changes
in repair are often cohesive sheets of enlarged cells that can form a “school of fish” appearance.

In lymphocytic cervicitis, a polymorphous population of lymphocytes is present and can be seen with or
without tingible body macrophages.

The changes seen in radiation can include markedly enlarged cells which maintain a normal nuclear to
cytoplasmic ratio. Binucleation or multinucleation is also commonly seen. Chronic radiation-induced
cellular changes can be seen indefinitely in the Pap test.

Changes associated with intrauterine devices can be either endometrial or endocervical columnar cells
that undergo irritation and then exfoliation. These cells can be in small groups or be seen as single cells
with a clean background. The cytoplasm frequently has large vacuolization that may even displace the
nucleus. Actinomyces-like organisms are frequently also seen.

Reactive cellular changes seen on a Pap test have been found to show an increased risk of CIN2-3 but
no significant increased risk of cancer.3 In some patients with a previous history of CIN, benign cellular
changes (BCC) may be of some significance, however, in patients with no significant prior cervical
abnormalities, a Pap test classified as BCC represents a reactive process.4

References
1. The Bethesda System for Reporting Cervical Cytology. 3rd edition

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2. Marshall LM, Cason Z, Cabaniss DE, Lemos LB, Benghuzzi HA. Reactive cell change in
cervicovaginal smears. Biomed Sci Instrum. 1997;33:298-304.
3. Moitry M, Jégu J, Averous G, et al. Reporting reactive cellular changes on smears among women
who undergo cervical cancer screening: results of a cohort study after seven years of follow-up.
Eur J Obstet Gynecol Reprod Biol. 2017;216:232-238. doi:10.1016/j.ejogrb.2017.07.032
4. Malik SN, Wilkinson EJ, Drew PA, Hardt NS. Benign cellular changes in Pap smears. Causes and
significance. Acta Cytol. 2001;45(1):5-8. doi:10.1159/000327180

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