PAP Smears/ HPV (Human
Papillomavirus)
The information provided by Advanced
Healthcare for Women and E. Daniel Biggerstaff, III, M.D. is for informational purposes
only. As each woman is unique, do not rely on this information for diagnosis and
treatment. We cannot guarantee the accuracy of the content and advise that you see a
qualified Health Care Professional for individual needs and care.
Cervical cancer is the tenth most common cancer in women in
the United States with approximately 13,000 new cases and 4,500 deaths per year. This is
in comparison to the second most common cancer and the fifth most common cause of cancer
deaths in the world. The reduction in number of deaths in the United States is due to
patient screening with Pap (Papanicolaou) smears.
A Pap smear is a painless test done at the time of a pelvic
examination. Currently, the specimen is obtained from the cervix using a small brush,
broom, spatula, or swab and placed on a microscope slide directly or into a special
solution (liquid-based system) to be processed later. Liquid-based systems improve the
quality of the Pap smear samples over the conventional smears placed directly on a
microscope slide.
The screening guidelines with a Pap smear for cervical cancer by the
American Cancer Society are:
- All women should have yearly Pap smears starting at age 18 or when
they begin having sex.
- A decision may be made to do the test less often if a woman has had 3
normal Pap smears in a row.
- Women who have had a hysterectomy (uterus removed) and those who are
post menopause should still have regular Pap smears.
The most significant causative factor for cervical cancer is human
papillomavirus or HPV. The infection can affect the mucous membranes (a delicate tissue)
of the cervix, vagina, vulva, anus, rectum, mouth and throat. Papillomaviruses can infect
almost any external skin surface in addition to the mucous membranes. It has now been
proven that HPV is the cause of the vast majority of cervical cancers. A few rare cancers
of the cervix are not related to HPV, with their cause unknown. The known risk factors for
cancer of the cervix include:
- HPV infection
- Multiple sexual partners
- Sexual activity at a young age
- Parity (having children)
- HIV (AIDS)
- Immune status (low immunity)
- Smoking
- History of other STD’s
- Oral contraceptive use
- Low socioeconomic status
- Alcoholism
- Poor diet
It has been shown that herpes simplex virus does not cause abnormal
Pap smears or cervical cancer.
A basic understanding of the kinds of tissue in the vagina, cervix,
and uterus is important to better understand what the results of a Pap smear imply. There
are two types of cells that are examined by the Pap smear. Squamous cells line the vagina
and are found on the face (or outside) of the cervix. When examined under a microscope,
the cells look similar to shingles on a roof. The vast majority of abnormal Pap smears
involves the squamous cells. Columnar or glandular cells are found inside the cervical
canal going up inside the uterus and inside the uterine cavity itself. When examined under
a microscope, these cells have the appearance of rows of Coke® bottles side-by-side. Less
than 1% of abnormal Pap smears involve the columnar or glandular cells.
Another area where terminology is important and can be confusing is
that of the Pap smear results and the results of the actual tissue biopsy. Over the years,
the reporting systems for the Pap smear and the tissue biopsy have changed. The Pap
reporting system used for many years was Class 1-5, with Class 1 being normal and Class 5
being invasive cancer. Both on the Pap smear and the tissue biopsy reports, dysplasia has
been (and in some cases still is) used to describe the abnormalities. Dysplasia is an
abnormal change in cells that may lead to cancer if left untreated and is described as
mild, moderate, and severe. Carcinoma-in-situ means superficial cancer and is treated with
removal of the affected area of the cervix. To make things more confusing, CIN or cervical
intraepithelial neoplasia is a more recent classification system to describe the tissue
diagnosis. CIN I corresponds to mild dysplasia, CIN II to moderate dysplasia, and CIN III
to severe dysplasia/carcinoma-in-situ.
The current system for reporting Pap smears is called TBS (The
Bethesda System) and was established in 2001. The results of the PAP smear (Bethesda 2001
nomenclature) may be returned as follows:
PAP Result |
Description |
| Negative |
negative for pre-cancer or cancer – inflammation
or non-HPV infection may be present |
| ASC-US |
atypical squamous cells - uncertain significance may be
due to irritation or infection, although other more serious causes cannot be ruled out |
| ASC-H |
atypical squamous cells – HSIL cannot be excluded |
| LSIL1 |
low-grade squamous intraepithelial lesion –
includes HPV/mild dysplasia/CIN I (cervical intraepithelial neoplasia) |
| HSIL2 |
high grade squamous intraepithelial lesion –
includes moderate and severe dysplasia/carcinoma-in-situ) |
| Squamous cell carcinoma3 |
cancer of the cervix |
1 Low-grade lesions (LGSIL) tend to be seen in
younger women (teens and 20s),
2high-grade lesions (HGSIL) in women in their 30s and
40s, and
3invasive cancers in 50s and 60s. In rare instances,
invasive cancer may be seen in young patients.
PAP Result |
Description |
| AGC - NOS |
atypical glandular cells – non-specific |
| AGC |
favor neoplastic atypical glandular cells – favor
tumor |
| AIS |
adenocarcinoma-in-situ – superficial cancer of the
glandular cells |
| Adenocarcinoma |
cancer of the glandular cells |
| HPV |
(Human PapillomaVirus) |
HPV is easily transmitted (usually by sexual intercourse), has
a high spontaneous remission rate (goes away by itself), may be present for many years,
and causes cancer in relatively few cases (compared to the number of women infected with
the virus). Most HPV infections go away by themselves, with the patients never knowing
they had the infection. There is currently no treatment for the virus. Approximately 5% of
infected women have persistence of the virus and are at risk for developing dysplasia
and/or cancer. It should be noted that transmission of the virus does not require sexual
penetration or intercourse but can occur with only intimate contact.
HPV types - there are different forms of the virus called types. The
HPV types were numbered in the order they were discovered. The most common low-risk HPV
types include 6 and 11 and are not likely to cause cancer. The low risk types are commonly
found in venereal warts (condyloma) on the vulva and are found in 20% of women who have
LGSIL (see above). The most common high-risk HPV types include 16 and 18 and have the
potential to cause cancer. High-risk HPV types are found in 80% of the women who have
LGSIL and almost all who have HGSIL and cervical cancer. HPV typing is performed using a
special DNA test.
Evaluation of Abnormal PAP Smears
When a woman has ASC-US, she should be tested for high-risk HPV
types from the liquid remaining in the Pap collection bottle. If the test is negative for
high-risk HPV types, the patient should have a repeat Pap in 12 months. If the test is
positive for high-risk HPV types, the patient should have a colposcopy. Colposcopy is a
procedure done in the office using a special microscope with a high-intensity light. The
cervix is examined, a biopsy is obtained from abnormal areas seen at the time of the
procedure. If a woman is post-menopausal and has ASC-US on Pap smear, she should be
treated with estrogen cream for three weeks and have the Pap smear repeated one week
following treatment. To assure no lesions are being missed, a second repeat Pap smear
should be performed in 4-6 months. If ASC-US persists on Pap smear, colposcopy should be
performed. A woman who is immunosuppressed (patient is HIV positive or certain other
medical conditions are present) and has ASC-US on Pap smear, she should have a colposcopy.
When ASC-H is present, a colposcopy should be performed .
All patients with AGC should have colposcopy and endocervical
sampling. Endocervical sampling is performed by scraping the canal inside the cervix with
a special instrument called a curette. If atypical endometrial cells (cells from the
cavity of the uterus) are reported and/or if the patient has abnormal vaginal bleeding,
the lining of the cavity of the uterus should be biopsied. In certain cases, other
procedures may be appropriate with AGC. These may include conization of the cervix,
ultrasound examination, and hysteroscopy.
Women with LGSIL should have a colposcopy. Endocervical sampling is
performed along with the colposcopy. If CIN (cervical intraepithelial neoplasia) is not
diagnosed on biopsy, Pap smear may be repeated at 6 and 12 months, or HPV testing may be
done at 12 months. As with ASC-US, if a woman is post-menopausal and has LGSIL on Pap
smear, she should be treated with estrogen cream for three weeks and have the Pap smear
repeated one week following treatment. To assure no lesions are being missed, a second
repeat Pap smear should be performed in 4-6 months and colposcopy performed for
persistence of the LGSIL. Teens are at virtually no risk for cervical cancer and may
therefore be managed more conservatively. Choices for teens with LGSIL include colposcopy,
repeat Pap at 6 and 12 months, or HPV testing at 12 months.
HGSIL requires colposcopy and endocervical sampling. If CIN II or
greater is not confirmed on biopsy, the Pap smear , the biopsy, and the colposcopy should
be reviewed. If the differences cannot be explained, a LEEP (loop electrode excision
procedure) should be considered. If the differences cannot be explained in teens, a repeat
Pap with colposcopy every 4-6 months for a year is acceptable because of the low incidence
of cervical cancer. HGSIL in pregnancy should be evaluated and treated by a physician who
has special expertise in this situation.
Treatment of Abnormal PAP Smears
Treatment of CIN may be with excisional techniques such as LEEP,
cold-knife conization, or laser excison; or with ablative techniques such as laser
vaporization or cryocautery. Excisional techniques provide a specimen that is sent to the
laboratory, whereas an ablative technique destroys the tissue. If there is any uncertainty
whether or not invasive cancer is present, an excisional technique should be used.
Invasive cervical cancer should be treated by a gynecologic oncologist.
Follow-up after treatment of CIN should be with Pap and colposcopy
in 3-4 months, and then follow-up Pap smears every 4-6 months for the first year. If
colposcopy is negative at the initial post-treatment visit and two sequential Pap smears
are normal, annual Pap screening can be resumed.
__________________
*Much of the above information was obtained from Advances in the
Screening, Diagnosis, and Treatment of Cervical Disease Monograph, by the Association of
Professors of Gynecology and Obstetrics. Copyright ć 2002
E. Daniel Biggerstaff III, M.D.
August 9, 3003 |
