The PAP smear is important because (in simple terms) it
screens for Human Papillomavirus (HPV) & Cervical Cancer. In this article is explained how the PAP more specifically:
- Screens for ASC-H to determines the need for colposcopy to rule out HSIL..
- Differentiates between LSIL vs. HSIL. HSIL is
indication for loop electrosurgical excision procedures (LEEP).
- Identifies women with a negative histology, but
clinical evidence of viral (e.g. HPV) persistence and risk for progression
(Solomon et al, 2002). Colposcopy is indicated.
Of the many HPV subtypes, there are 4 that account for 80% of all genital warts and/or invasive cervical cancers, HPV16 & HPV18 definitively implicated in cervical dyplasias & cancer. Additional risk factors for developing cervical cancer are smoking, multiple sexual partners, DES exposure, hysterectomy for malignancy, a previously abnormal PAP, and history of sexually transmitted infections (STIs).
Ladies First Cervical Care Cycle
(2011) adds: history of sexual abuse, Immunodeficiency or HIV infection, and history of non-adherence to recommended medical care. HPV is a sexually transmitted disease, so it is recommended (by Western
Medicine Guidelines) that females (and males) be tested for [and vaccinated against HPV] before they become sexually active.
The PAP uses the Bethesda
System (American Society of Cytopathology, 2001), which standardizes &
categorizes the terminology used to report & evaluate PAP smear findings. This system has 3 major reporting elements (Ladies First, 2011):
- Specimen Adequacy
- General Categorization
- Interpretation of Result as:
- Negative for Intraepithelial Lesion
- Negative "Other than or reactive to"
- Positive for Squamous Abnormality
- Other Neoplasms
1. SPECIMEN ADEQUACY (Solomon
et al, 2002):
- Conventional Method (cervical scraping) = 8,000 to 12,000 cells quantified
- Liquid-based Method (cervical wash) = 5000 cells quantified
- Less than
Adequate Specimen = lacks endocervical & squamous cells, squamous
metaplasia, or endocervical transitional zone (T zone) cells.
- Specimen Notations (Solomon
et al, 2002):
-> Unlabeled specimen is always noted as
/ Inadequate number of cells from the endocervical T zone.
Adequate is quantified as 10 endocervical or squamous metaplastic cells.
Field Obscured by blood or
inflammation. An obscured field is: Satisfactory
even if 50 to 75% of the epithelial cells are not visualize. Unsatisfactory
when greater than 75% of the epithelial cells are not visualized.
2. & 3. General Categorization & Interpretation:
- NEGATIVE INTRAEPITHELIAL LESION means there ARE NO morphological cellular
changes or evidence of (squamous cell) neoplasia. The notation “other than REACTIVE to…” is added if any
cell changes that pose an epidemiological risk are due to an organism(s) or
Organisms that T zone cells can
react to include:
- Herpes simplex virus (HSV)
- Trichomonas vaginalis
- Candida species
- Vaginal flora suggestive of bacterial vaginosis or
Conditions that T zone cells can
react to include:
- Intrauterine contraceptive devices (IUD)
- post hysterectomy
- perimenopausal glandular atrophy
- POSITIVE SQUAMOUS CELL ABNORMALITIES:
Squamous Cells (ASC). All ASC abnormalities are more marked than “
REACTIVE” finding and are suggestive of but less marked than a Squamous Cell
Intraepithelial Lesion (SIL). Solomon et al (2002) state that (1) 10 to 20% of women with ASC have cervical intraepithelial neoplasia (noninvasive squamous cell abnormality), (2) 1 in 1000 women with ASC have invasive cancer, and (3) ASC has a high positive predictive value of CIN2 or CIN3 (see below).
ASC SUB- CATEGORIES:
-> Atypical Squamous Cells of Undetermined
-> Atypical Squamous Cells with High-grade
Squamous Cell Intraepithelial Lesion/HSIL Not Ruled Out (ASC-H).
ASC-H classification is a very important intermediary between ASC-U above and HSIL below because 5% to 10% of ASC turns out to be HSIL (Solomon et al,
- POSITIVE SQUAMOUS INTRAEPITHELIAL LESIONS (SIL)
-> Low-grade Squamous intraepithelial Lesions (LSIL).
Most cervical dysplasias that are LSIL, especially among young women, are
self-limiting HPV infection with the reliability of the
occurrence reproducible - unlike HSIL. (Solomon et al, 2001).
-> High–grade Squamous Intraepithelial Lesions (HSIL). These encompass moderate to severe dysplasias, carcinoma in situ, and squamous cell
- ATYPICAL GLANDULAR CELLS (AGC) & AGC-UNDETERMINED SIGNIFICANCE (AGC-US). The PAP
smear is best to identify squamous & epithelial lesions/ cancers of the endocervix (T zone) and NOT epithelial abnormalities of glandular,
endocervical, endometrial cells of the uterus and ovaries etc. Therefore,
it is reported whenever endometrial glandular cells ARE found via PAP in women over 40 years old with or without SIL (Solomon et al, 2002).
Differentiating between cells of the T zone vs. cells of
glandular tissue determines treatment & prognosis. So a notation is made as
to whether the AGC appear favorable towards neoplasm. This is because, when
identified via a PAP smear, 20% to 30% of AGCs are associated with a high-grade
disease compared to ASC-US findings, and AGCs of Undetermined Significance (AGC-US) is probably
neoplastic (Solomon et al, 2002).
AGC & AGC-US SUB-CATEGORIES:
-> Atypical Cells (endocervical, endometrial, or
glandular) specified or not otherwise specified (NOS)
-> Atypical Cells (endocervical, endometrial, or
glandular) that favor neoplasm. Atypical endocervical cell have fewer
neoplasias (Solomon et al, 2002).
-> Endocervical Adenocarcinoma in Situ
(endocervical, endometrial, or extrauterine) NOS.
Reliability & Sensitivity of PAP Results
A pathologist interprets & reports PAP (and biopsy)
results. The mode of analysis of the PAP cytology specimen is automated,
computer generated, or via molecular testing (Solomon et al, 2001). The PAP is 68% - 80%
sensitive in detecting women with cervical intraepithelial neoplasia,
but sensitivity is also dependent upon the adequacy of the PAP smear sample (National
Cancer Institute, 2014).
This sensitivity means that 20% or more of women with cervical
neoplasia are missed. Hence the importance of scheduled screening
every 3 years or more frequently depending on the risk factors. On
the other hand, testing for the presence of HPV antibodies during a
PAP is 95% sensitive. Meaning only 5% of women with HPV are missed.
CERVICAL NEOPLASM VS. CANCER
The Cervical Intraepithelial
Neoplasia (CIN) 1,2,3 Grading System is NOT used in the Bethesda PAP system. The CIN system evaluates histology (tissue appearance) via biopsy vs. PAP cytology (cell appearance) via cervical scraping/wash. Biopsy is desired when when PAP results show POSITIVE SQUAMOUS INTRAEPITHELIAL LESION (SIL) and further qualify the lesion as:
- CN 1
= mild dysplasia
- CN 2=
- CN 3=
CIN terminology can be combined with Bethesda
terminology for management guidelines. For example, HPV dysplasia
would be categorized as CIN1 (Solomon et al, 2002). Lower Anogenital
Squamous Terminology (LAST) is another histology grading system that
is combined with Bethesda terminology for anorectal tissue neoplasia.
The most important histological finding upon biopsy is if
the dysplasia (abnormally growing) cells are invading surrounding tissue - if they are not, it is called in situ, which is technically not cancer yet
(Minarsik, 2014)! Dysplasic cells upon biopsy, can appear histologically
to-> to slightly different from -> to grossly different from their parent cells such that it is sometimes very
difficult for a pathologist to determine neoplasia and tissue of origin
(Minarsik, 2014) in order to diagnose:
- endocervical adenocarcinoma/ endocervical
adenocarcinoma in situ
- endometrial adeno-carcinoma
- extrauterine adeno-carcinoma
- adenocarcinoma, NOS
- adenocarcinoma in situ (AIS). There is
overlap between AIS and well-differentiated invasive endocervical
adenocarcinoma (Solomon et al, 2001).
INTEGRATIVE MEDICINE TIPS:
- Pearl Powder, a
classical Chinese herbal formula is the focus of a Phase
II study of a topical herbal cream for the treatment of HIV-related anal high-grade squamous intraepithelial lesion/aHSIL) and to prevent HPV-related anal cancer. Misha Ruth Cohen OMD LAc is a
lead investigator on a team with MDs at California Pacific Medical
Center, San Francisco California (Misha
Ruth Cohen Education Foundation):
American Society of Cytopathology. The 2001 Bethesda System. In NCI Bethesda System. Retrieved from
Obstetrics & Gynecology of Dothan. (2011). Cervicalcarecycle
from http://ladiesfirstproviders.vermont.gov/cervical-care/cycle (interactive web page no longer available).
Minarsik, (2014). Neoplasms I- IV: Sessions 11-14. In Medical School
Pathology. Retrieved from www.medicalschoolpathology.com/2014-2015MP4Archives/
National Cancer Institute. (2014). Cervical cancer
screening: Description of the evidence. Retrieved from www.cancer.gov/cancertopics/pdq/screening/cervical/HealthProfessional/page2
Solomon, D., Davey, D., Kurman, R., Moriarty, A., O’Connor,
D., Prey, ... Young, N. (2002). The 2001 Bethesda System terminology for reporting results of cervical
cytology. Journal of the American Medical Association 287:16.