**3. Incidence of positive gynecological cancers in examinees of Ningen Dock**

**Table 2** shows the cytologic and ultrasonographic findings of all subjects who visited the Ningen Dock in our institute between 2002 and 2016 [3, 4]. Of the cytology from cervix, 140 cases (0.8%) were found as abnormal. Among them, 127 cases were classified as low-grade cervical smear abnormalities: LSIL and HSIL were seen in 105 cases, ASC-US was seen in 22. Suspected malignancy of squamous cell was detected in five cases within this study period, while case of cervical adenocarcinoma was not found. No cytological abnormality categories were clustered in any specific age group. Endometrial smear showed hyperplasia suspicious in 2.7% cases.

and ultrasonographic abnormalities. Gynecologic cancer is detected in 0.03%, all of which were at the early stages (so-called CIN3). The very low incident is in good agreement with

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HPV stands for human papilloma virus, which is a group of more than 200 viruses. Most people will get a HPV infection during their lifetime, usually from sexual activity. Most of these infections do not need treatment, but they can cause genital warts. In some, however, HPV infection causes changes in the cervix that can develop into cervical cancer. HPV can infect the cells on the surface of the cervix and damage them, causing their appearance to change and lead to abnormalities in these cells over a number of years. These abnormalities are known as cervical intraepithelial neoplasia (CIN). These changes are classified according to their severity. The mean time between the virus infection and invasive cancer takes about 15 years, and within 2–4 years of detection 15.5–25.5% of low-grade epithelial lesions that become high-grade lesions. In some cases, these more severe changes can develop into cervical cancer. The progression of mild and severe changes to cancer takes many years so these abnormalities are known as precancerous [12–14]. HPV infection is most common in people in their late teens and early 20s [15, 16]. A study in Jordan, one of the most conservative and religious country, found that 0.8% of 1176 women aged 18–70 years are classified as ASC-US and 0.2% as LSIL. In our unique system Ningen Dock in Japan, symptom-free women undergo medical check-up at their own expense. Their educational tradition and high concern on sextransmitted infection, such as HPV, may restrict the likelihood of multiple sexual partners. This may be the most plausible explanation for extremely low incidence of dysplastic changes

As uterine enlargement, uterine myoma with or without adenomyosis are found in 20–25% of reproductive-age women, indicating that they are one of the most frequent women's lower abdominal tumor [17–19]. The women with myoma do not necessarily complain of symptoms, and even large ones may go undetected by the patient, particularly if she is obese. Myoma-linked symptoms (abdominal distention, vaginal bleeding, constipation, and peritoneal irritation) depend on their location, size, and state of presentation; symptoms are present in 35–50% of patients with myomas. Ovarian tumors, cystic or solid, also seldom cause symptoms. Although the ovarian enlargement is frequently undetected by the patients, the diagnosis of these tumors is not usually difficult by ultrasonographic examination at physical check-up. Our subjects showed lower frequency of uterine enlargement and ovarian tumors.

Many previous trials demonstrated a reduction in the average overall mortality among ovarian cancer patients screened with an annual sequential, multimodal strategy that tracked biomarkers CA125 over time, where increasing serum CA125 levels prompted ultrasound [20–23]. A critical factor which could contribute to false negatives is that many aggressive ovarian cancers are believed to arise from epithelial cells on the fimbriae of the fallopian tube, which are not readily imaged. In addition, because, only a fraction of metastatic tumors may reach an imaging device-detectable size before they metastasize, annual screening with imaging diagnosis may fail to detect a large fraction of early stage ovarian cancers [24, 25]. The ability to detect ovarian carcinomas before they metastasize is critical and future efforts toward improving screening should focus on identifying unique features specific to aggressive, early

the primary report in some Ningen Docks [1, 11].

and cervical cancer found in our study group of women.

Uterine enlargement was the most frequently detected gynecologic finding, with a peak reaching approximately 25% in 40–49 years age group. The uterine abnormalities had a tendency to decrease in those aged over 60 years. Ovarian tumor (including solid and cystic enlargement) was detected in 5.2–8.0% of those in the age groups of 30–49 years, while those aged over 60 years had less frequency. In 91.3% participants, no gynecologic abnormality was detected.

The abnormal cytologic findings, including dysplastic changes and cervical cancer, are observed to be very low compared with other studies performed in developed countries (3.4–9%) [5–10]. Our findings based on 2011–2016 Ningen Dock records are similar to those of the former observations, and most of participants (95.6%) revealed no gynecological cytology


Between January 2002 and December 2016, 16,520 asymptomatic women, aged 18–85, visited the Ningen Dock in Matsunami General Hospital for their gynecological health check-up. \* Including vaginosis, leukoplakie, Bartholin cyst, posthysterectomy, cervical polyp, and prolaps/ptosis. LSIL, low-grade squamous intraepithelial lesion; HSIL, highgrade squamous intraepithelial lesion; ASC-US, atypical squamous cells of undetermined significance; SCC, cervical squamous cell carcinoma; AGC, atypical glandular cells; EM; endometrium. Modified from our previous reports [3, 4].

**Table 2.** Gynecologic findings of participants distributed by age group.

and ultrasonographic abnormalities. Gynecologic cancer is detected in 0.03%, all of which were at the early stages (so-called CIN3). The very low incident is in good agreement with the primary report in some Ningen Docks [1, 11].

were found as abnormal. Among them, 127 cases were classified as low-grade cervical smear abnormalities: LSIL and HSIL were seen in 105 cases, ASC-US was seen in 22. Suspected malignancy of squamous cell was detected in five cases within this study period, while case of cervical adenocarcinoma was not found. No cytological abnormality categories were clustered in any

Uterine enlargement was the most frequently detected gynecologic finding, with a peak reaching approximately 25% in 40–49 years age group. The uterine abnormalities had a tendency to decrease in those aged over 60 years. Ovarian tumor (including solid and cystic enlargement) was detected in 5.2–8.0% of those in the age groups of 30–49 years, while those aged over 60 years had less frequency. In 91.3% participants, no gynecologic abnormality was

The abnormal cytologic findings, including dysplastic changes and cervical cancer, are observed to be very low compared with other studies performed in developed countries (3.4–9%) [5–10]. Our findings based on 2011–2016 Ningen Dock records are similar to those of the former observations, and most of participants (95.6%) revealed no gynecological cytology

> **than normal**

26 (1.8) 4 (0.3) 3 (0.2) 0 1 (<0.1) 80 (5.6) 74 (5.2) 68 (4.7)

37 (2.6) 6 (0.4) 3 (0.2) 1 (<0.1) 2 (0.1) 361 (25.2) 114 (8.0) 139 (9.7)

22 (1.5) 4 (0.3) 9 (0.6) 2 (0.1) 35 (2.4) 164 (11.4) 42 (2.9) 95 (6.6)

4 (0.3) 0 2 (0.1) 1 (<0.1) 0 44 (30.7) 8 (0.6) 16 (1.1)

1433 (8.7)

**tumor and abnormalities** **Ovary tumor and abnormalities**

Including vaginosis, leukoplakie, Bartholin cyst,

**Others\***

specific age group. Endometrial smear showed hyperplasia suspicious in 2.7% cases.

48 Cervical Cancer - Screening, Treatment and Prevention - Universal Protocols for Ultimate Control

**No. (%) Cytology Uterine** 

<19 12 (<0.1) 1 (<0.1) 0 0 0 0 0 2 (0.1) 0 20–29 794 (4.8) 9 (0.6) 0 5 (0.3) 1 (<0.1) 0 6 (0.4) 18 (1.3) 13 (0.9)

70–79 228 (1.4) 0 0 0 0 0 5 (0.3) 1 (<0.1) 6 (0.4) > 80 18 (<0.1) 0 0 0 0 0 0 0 0

Total 16,520 (100) 99 (0.6) 14 (<0.1) 22 (0.1) 5 (<0.1) 37 (0.2) 660 (4.0) 259 (1.6) 337 (2.0)

Between January 2002 and December 2016, 16,520 asymptomatic women, aged 18–85, visited the Ningen Dock in

posthysterectomy, cervical polyp, and prolaps/ptosis. LSIL, low-grade squamous intraepithelial lesion; HSIL, highgrade squamous intraepithelial lesion; ASC-US, atypical squamous cells of undetermined significance; SCC, cervical squamous cell carcinoma; AGC, atypical glandular cells; EM; endometrium. Modified from our previous reports [3, 4].

Matsunami General Hospital for their gynecological health check-up. \*

**Table 2.** Gynecologic findings of participants distributed by age group.

**Cervix EM LSIL HSIL ASC-US SCC Other** 

detected.

**Age group (years)**

30–39 3172

40–49 6217

50–59 4615

60–69 1464

(19.2)

(37.6)

(27.9)

(8.9)

HPV stands for human papilloma virus, which is a group of more than 200 viruses. Most people will get a HPV infection during their lifetime, usually from sexual activity. Most of these infections do not need treatment, but they can cause genital warts. In some, however, HPV infection causes changes in the cervix that can develop into cervical cancer. HPV can infect the cells on the surface of the cervix and damage them, causing their appearance to change and lead to abnormalities in these cells over a number of years. These abnormalities are known as cervical intraepithelial neoplasia (CIN). These changes are classified according to their severity. The mean time between the virus infection and invasive cancer takes about 15 years, and within 2–4 years of detection 15.5–25.5% of low-grade epithelial lesions that become high-grade lesions. In some cases, these more severe changes can develop into cervical cancer. The progression of mild and severe changes to cancer takes many years so these abnormalities are known as precancerous [12–14]. HPV infection is most common in people in their late teens and early 20s [15, 16]. A study in Jordan, one of the most conservative and religious country, found that 0.8% of 1176 women aged 18–70 years are classified as ASC-US and 0.2% as LSIL. In our unique system Ningen Dock in Japan, symptom-free women undergo medical check-up at their own expense. Their educational tradition and high concern on sextransmitted infection, such as HPV, may restrict the likelihood of multiple sexual partners. This may be the most plausible explanation for extremely low incidence of dysplastic changes and cervical cancer found in our study group of women.

As uterine enlargement, uterine myoma with or without adenomyosis are found in 20–25% of reproductive-age women, indicating that they are one of the most frequent women's lower abdominal tumor [17–19]. The women with myoma do not necessarily complain of symptoms, and even large ones may go undetected by the patient, particularly if she is obese. Myoma-linked symptoms (abdominal distention, vaginal bleeding, constipation, and peritoneal irritation) depend on their location, size, and state of presentation; symptoms are present in 35–50% of patients with myomas. Ovarian tumors, cystic or solid, also seldom cause symptoms. Although the ovarian enlargement is frequently undetected by the patients, the diagnosis of these tumors is not usually difficult by ultrasonographic examination at physical check-up. Our subjects showed lower frequency of uterine enlargement and ovarian tumors.

Many previous trials demonstrated a reduction in the average overall mortality among ovarian cancer patients screened with an annual sequential, multimodal strategy that tracked biomarkers CA125 over time, where increasing serum CA125 levels prompted ultrasound [20–23]. A critical factor which could contribute to false negatives is that many aggressive ovarian cancers are believed to arise from epithelial cells on the fimbriae of the fallopian tube, which are not readily imaged. In addition, because, only a fraction of metastatic tumors may reach an imaging device-detectable size before they metastasize, annual screening with imaging diagnosis may fail to detect a large fraction of early stage ovarian cancers [24, 25]. The ability to detect ovarian carcinomas before they metastasize is critical and future efforts toward improving screening should focus on identifying unique features specific to aggressive, early stage tumors, as well as improving imaging sensitivity to allow for detection of tubal lesions. So far, multimodal screening strategy in which blood-based assay is positive, and subsequent imaging examination may prove useful in detecting early stage cases [20–22, 25].

screening reduces the cervical cancer incidence worldwide [38–42]. The mean time between the virus infection and invasive cancer takes about 15 years, and within 2–4 years of detection 15.5–25.5% of low-grade epithelial lesions become high-grade lesions. In some cases, these more severe changes can develop into cervical cancer [5–10]. A routine screening test includes cytology smear test used for the detection of early cervical abnormalities (precancerous dysplastic changes) of the uterine cervix [5–10]. The screening is a relatively simple, low cost, and noninvasive method. Concurrent transvaginal ultrasonography for detection of ovarian and uterine tumors, the cervical and endometrial cytology smear tests attenuate the probability of

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Ningen Dock check-ups provide an occasion to realize preventive medicine. An important aim of gynecological health check-up is to provide support in improving the risk factors that accelerate the risk of outbreak of a malignant disease at an early stage, before subjective symptoms become apparent. Additionally, meticulous educational guidance is provided to match individual living patterns, education level, and ways of thinking. Ningen Dock can also conceive of time in the future when more appropriate and effective educational advice could be continuously provided according to a participant cultural background and lifestyle habits,

Qualitative evaluation of Ningen Dock Facilities consists of documentation and an inspection. These are administration of the facility, satisfaction and safety of examinees, and quality of check-up and follow-up [1]. Recently, the usefulness of Ningen Dock has greatly increased not only in the primary, but also in the secondary prevention of non-communicable diseases due to advances in diagnostic medical technology and therapeutic medicine. However, one of the problems is that relatively large numbers of Ningen Dock examinees who require a second, more detailed examination do not have the examination that has been recommended. For instance, only 61% of the Ningen Dock examinees who required total colon fiberscope as a second, detailed examination due to a positive fecal occult blood test underwent it. Similar tendencies were recognized for almost all Ningen Dock examinations [11]. The reason why Ningen Dock examinees who need second, more detailed examinations do not have them may be that most of them do not understand the importance of such examinations for the early detection of non-communicable diseases and their risk factors because we do not adequately explain the need for more detailed examinations to examinees. Therefore, better education of examinees may be urgently needed in order to further increase the usefulness of Ningen Dock. In Japan, there are also free physical check-up programs of cancer screening, by which asymptomatic participants undergo a medical examination at public expense. Takagi et al. [43] reported similar data using records of the public expense-covered free examination, and suggested that active gynecologic check-up and adequate follow-up programs even against symptom-free population can reduce in the probability of malignant disease development. Their findings from representative population of high-attitude toward screening, but non-high income, may

The present data are from subject to the limitations of any analysis of self-covered health check-up survey data from participants of Ningen Dock in Japan. Although data are weighted to reflect the Japanese population, the extent to which results are generalizable is no known. Future studies, extended to non-Asian, should attempt to oversample racial minorities and include a detailed assessment of gynecologic cancer screening history and follow-up treatment.

developing gynecological malignant diseases.

via collaboration with health-related public services.

give new insight into the terms of public health.
